Publication Cover
Redox Report
Communications in Free Radical Research
Volume 29, 2024 - Issue 1
2,037
Views
0
CrossRef citations to date
0
Altmetric
Review Article

Integrated approach to reducing polypharmacy in older people: exploring the role of oxidative stress and antioxidant potential therapy

ORCID Icon, , ORCID Icon, , & ORCID Icon

References

  • United Nations. World social report 2023: leaving no one behind in an ageing world | UN DESA Publications [Internet]. 2023. Available from: https://desapublications.un.org/publications/world-social-report-2023-leaving-no-one-behind-ageing-world.
  • Chowdhury SR, Chandra Das D, Sunna TC, et al. Global and regional prevalence of multimorbidity in the adult population in community settings: a systematic review and meta-analysis. eClinicalMedicine. 2023;57:101860–101860. doi:10.1016/j.eclinm.2023.101860
  • Makovski TT, Schmitz S, Zeegers MP, et al. Multimorbidity and quality of life: systematic literature review and meta-analysis. Ageing Res Rev. 2019;53:100903–100903. doi:10.1016/j.arr.2019.04.005
  • López-Otín C, Blasco MA, Partridge L, et al. The hallmarks of aging. Cell. 2013;153:1194–1217. doi:10.1016/j.cell.2013.05.039
  • Delara M, Murray L, Jafari B, et al. Prevalence and factors associated with polypharmacy: a systematic review and meta-analysis. BMC Geriatr. 2022;22:601. doi:10.1186/s12877-022-03279-x
  • Midão L, Brochado P, Almada M, et al. Frailty status and polypharmacy predict all-cause mortality in community dwelling older adults in Europe. Int J Environ Res Public Health. 2021;18:3580. doi:10.3390/ijerph18073580
  • Doumat G, Daher D, Itani M, et al. The effect of polypharmacy on healthcare services utilization in older adults with comorbidities: a retrospective cohort study. BMC Prim Care. 2023;24:120. doi:10.1186/s12875-023-02070-0
  • Sinnott C, Mc Hugh S, Browne J, et al. GPs’ perspectives on the management of patients with multimorbidity: systematic review and synthesis of qualitative research. BMJ Open. 2013;3:e003610. doi:10.1136/bmjopen-2013-003610
  • O’Mahony D, Rochon PA. Prescribing cascades: we see only what we look for: we look for only what we know. Age Ageing. 2022;51:afac138. doi:10.1093/ageing/afac138
  • Kennedy BK, Berger SL, Brunet A, et al. Geroscience: linking aging to chronic disease. Cell. 2014;159:709–713. doi:10.1016/j.cell.2014.10.039
  • Van Der Graaf PH, Gabrielsson J. Pharmacokinetic–pharmacodynamic reasoning in drug discovery and early development. Future Med Chem. 2009;1:1371–1374. doi:10.4155/fmc.09.124
  • O’Connor A, O’Moráin C. Digestive function of the stomach. Dig Dis Basel Switz. 2014;32:186–191. doi:10.1159/000357848
  • Nandagopalan PA, Magdalene KF, Binu A. Effect of aging on the quantitative number of Brunner’s glands. J Clin Diagn Res JCDR. 2014;8:4–4.
  • Zhou R, Moench P, Heran C, et al. pH-Dependent dissolution in vitro and absorption in vivo of weakly basic drugs: development of a canine model. Pharm Res. 2005;22:188–192. doi:10.1007/s11095-004-1185-3
  • Pang J, Dalziel G, Dean B, et al. Pharmacokinetics and absorption of the anticancer agents dasatinib and GDC-0941 under various gastric conditions in dogs - reversing the effect of elevated gastric pH with betaine HCl. Mol Pharm. 2013;10:4024–4031. doi:10.1021/mp400356m
  • Phillips RJ, Kieffer EJ, Powley TL. Aging of the myenteric plexus: neuronal loss is specific to cholinergic neurons. Auton Neurosci Basic Clin. 2003;106:69–83. doi:10.1016/S1566-0702(03)00072-9
  • Bernard CE, Gibbons SJ, Gomez-Pinilla PJ, et al. Effect of age on the enteric nervous system of the human colon. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2009;21:746-e46. https://pubmed-ncbi-nlm-nih-gov.uchile.idm.oclc.org/19220755/
  • Wiskur B, Greenwood-Van Meerveld B. The aging colon: the role of enteric neurodegeneration in constipation. Curr Gastroenterol Rep. 2010;12:507–512. doi:10.1007/s11894-010-0139-7
  • McLachlan AJ, Bath S, Naganathan V, et al. Clinical pharmacology of analgesic medicines in older people: impact of frailty and cognitive impairment. Br J Clin Pharmacol. 2011;71:351–364. doi:10.1111/j.1365-2125.2010.03847.x
  • Farage MA, Miller KW, Elsner P, et al. Characteristics of the aging skin. Adv Wound Care. 2013;2:5–10. doi:10.1089/wound.2011.0356
  • Miller MR. Structural and physiological age-associated changes in aging lungs. Semin Respir Crit Care Med. 2010;31:521–527. doi:10.1055/s-0030-1265893
  • Hochhegger B, de Meireles GP, Irion K, et al. O tórax e o envelhecimento: manifestações radiológicas. J Bras Pneumol. 2012;38:656–665. doi:10.1590/S1806-37132012000500016
  • Sprung J, Gajic O, Warner DO. Review article: age related alterations in respiratory function - anesthetic considerations. Can J Anesth. 2006;53:1244–1257. doi:10.1007/BF03021586
  • Ishaq A, Schröder J, Edwards N, et al. Dietary restriction ameliorates age-related increase in DNA damage,: senescence and inflammation in mouse adipose tissuey. J Nutr Health Aging. 2018;22:555–561. doi:10.1007/s12603-017-0968-2
  • Hughes VA, Roubenoff R, Wood M, et al. Anthropometric assessment of 10-y changes in body composition in the elderly. Am J Clin Nutr. 2004;80:475–482. doi:10.1093/ajcn/80.2.475
  • Lei SF, Liu MY, Chen XD, et al. Relationship of total body fatness and five anthropometric indices in Chinese aged 20–40 years: different effects of age and gender. Eur J Clin Nutr. 2006;60:511–518. doi:10.1038/sj.ejcn.1602345
  • Raguso CA, Kyle U, Kossovsky MP, et al. A 3-year longitudinal study on body composition changes in the elderly: role of physical exercise. Clin Nutr. 2006;25:573–580. doi:10.1016/j.clnu.2005.10.013
  • Mitchell WK, Williams J, Atherton P, et al. Sarcopenia: dynapenia, and the impact of advancing age on human skeletal muscle size and strength; a quantitative review. Front Physiol. 2012;3:260–260. doi:10.3389/fphys.2012.00260
  • Rodríguez-Julbe MC, Ramírez-Ronda CH, Arroyo E, et al. Antibiotics in older adults. P R Health Sci J. 2004;23:25–33.
  • Hanratty CG, McGlinchey P, Johnston GD, et al. Differential pharmacokinetics of digoxin in elderly patients. Drugs Aging. 2000;17:353–362. doi:10.2165/00002512-200017050-00003
  • Greenblatt DJ, Harmatz JS, Zhang Q, et al. Slow accumulation and elimination of diazepam and its active metabolite with extended treatment in the elderly. J Clin Pharmacol. 2021;61:193–203. doi:10.1002/jcph.1726
  • Cabrerizo S, Cuadras D, Gomez-Busto F, et al. Serum albumin and health in older people: review and meta analysis. Maturitas. 2015;81:17–27. doi:10.1016/j.maturitas.2015.02.009
  • Chudzik M, Maciązek-Jurczyk M, Pawełczak B, et al. Spectroscopic studies on the molecular ageing of serum albumin. Mol Basel Switz. 2016;22:E34–E34.
  • Silva-Fhon JR, Rojas-Huayta VM, Aparco-Balboa JP, et al. Sarcopenia and blood albumin: a systematic review with meta-analysis. Biomed Rev Inst Nac Salud. 2021;41:590–603.
  • Park HN, Song MJ, Choi YE, et al. LRG1 promotes ECM integrity by activating the TGF-β signaling pathway in fibroblasts. Int J Mol Sci. 2023;24:12445. doi:10.3390/ijms241512445
  • Grandison MK, Boudinot FD. Age-related changes in protein binding of drugs. Clin Pharmacokinet 2000. 2012;383:271–290.
  • Benet LZ, Hoener BA. Changes in plasma protein binding have little clinical relevance. Clin Pharmacol Ther. 2002;71:115–121. doi:10.1067/mcp.2002.121829
  • Warren A, Chaberek S, Ostrowski K, et al. Effects of old age on vascular complexity and dispersion of the hepatic sinusoidal network. Microcirculation. 2008;15:191–191. doi:10.1080/10739680701600856
  • Tajiri K, Shimizu Y. Liver physiology and liver diseases in the elderly. World J Gastroenterol. 2013;19:8459–8467. doi:10.3748/wjg.v19.i46.8459
  • Rattanacheeworn P, Kerr SJ, Kittanamongkolchai W, et al. Quantification of CYP3A and drug transporters activity in healthy young, healthy elderly and chronic kidney disease elderly patients by a microdose cocktail approach. Front Pharmacol. 2021;12:726669. doi:10.3389/fphar.2021.726669
  • Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev. 2009;41:67–76. doi:10.1080/03602530902722679
  • Long DA, Mu W, Price KL, et al. Blood vessels and the aging kidney. Nephron Exp Nephrol. 2005;101:e95–e99. doi:10.1159/000087146
  • Emamian SA, Nielsen MB, Pedersen JF, et al. Kidney dimensions at sonography: correlation with age,: sex, and habitus in 665 adult volunteers. AJR. Am J Roentgenol. 2013;160:83–86. doi:10.2214/ajr.160.1.8416654
  • Gourtsoyiannis N, Prassopoulos P, Cavouras D, et al. The thickness of the renal parenchyma decreases with age: a CT study of 360 patients. AJR. Am J Roentgenol. 2013;155:541–544. doi:10.2214/ajr.155.3.2117353
  • Roseman DA, Hwang SJ, Oyama-Manabe N, et al. Clinical associations of total kidney volume: the Framingham heart study. Nephrol Dial Transplant. 2017;32:1344–1350.
  • Zhou XJ, Rakheja D, Yu X, et al. The aging kidney. Kidney Int. 2008;74:710–720. doi:10.1038/ki.2008.319
  • Denic A, Lieske JC, Chakkera HA, et al. The substantial loss of nephrons in healthy human kidneys with aging. J Am Soc Nephrol. 2017;28:313–320. doi:10.1681/ASN.2016020154
  • Glassock RJ, Rule AD. The implications of anatomical and functional changes of the aging kidney: with an emphasis on the glomeruli. Kidney Int. 2012;82:270–277. doi:10.1038/ki.2012.65
  • Bolignano D, Mattace-Raso F, Sijbrands EJG, et al. The aging kidney revisited: a systematic review. Ageing Res Rev. 2014;14:65–80. doi:10.1016/j.arr.2014.02.003
  • Glassock RJ, Rule AD. Aging and the kidneys: anatomy, physiology and consequences for defining chronic kidney disease. Nephron. 2016;134:25–29. doi:10.1159/000445450
  • O’Sullivan ED, Hughes J, Ferenbach DA. Renal aging: causes and consequences. J Am Soc Nephrol JASN. 2017;28:407–420. doi:10.1681/ASN.2015121308
  • James MT, Hemmelgarn BR, Wiebe N, et al. Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study. Lancet. 2010;376:2096–2103. doi:10.1016/S0140-6736(10)61271-8
  • López-Otín C, Blasco MA, Partridge L, et al. Hallmarks of aging: an expanding universe. Cell. 2023;186:243–278. doi:10.1016/j.cell.2022.11.001
  • Martínez de Toda I, Ceprián N, Díaz-Del Cerro E, et al. The role of immune cells in oxi-inflamm-aging. Cells. 2021;10:2974. doi:10.3390/cells10112974
  • Sies H, Berndt C, Jones DP. Oxidative stress. Annu Rev Biochem. 2017;86:715–748. doi:10.1146/annurev-biochem-061516-045037
  • Jones DP. Radical-free biology of oxidative stress. Am J Physiol Cell Physiol. 2008;295:C849–C868. doi:10.1152/ajpcell.00283.2008
  • Liu X, Hussain R, Mehmood K, et al. Mitochondrial-endoplasmic reticulum communication-mediated oxidative stress and autophagy. BioMed Res Int. 2022;2022.6459585. doi:10.1155/2022/6459585. PMID: 36164446.
  • Sies H. Chapter 13 - Oxidative stress: eustress and distress in redox homeostasis. In: Fink G, editor. Stress physiol biochem pathol. Düsseldorf, Germany: Academic Press; 2019. p. 153–163. [cited 2023 Nov 11]. Available from: https://www.sciencedirect.com/science/article/pii/B9780128131466000138.
  • Janaszak-Jasiecka A, Płoska A, Wierońska JM, et al. Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets. Cell Mol Biol Lett. 2023;28:21. doi:10.1186/s11658-023-00423-2
  • Liu J, Kang R, Tang D. Signaling pathways and defense mechanisms of ferroptosis. FEBS J. 2022;289:7038–7050. doi:10.1111/febs.16059
  • Sies H. Total antioxidant capacity: Appraisal of a Concept12. J Nutr. 2007;137:1493–1495. doi:10.1093/jn/137.6.1493
  • Suzuki T, Yamamoto M. Stress-sensing mechanisms and the physiological roles of the Keap1–Nrf2 system during cellular stress. J Biol Chem. 2017;292:16817–16824. doi:10.1074/jbc.R117.800169
  • Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J. 2016;151:1–22.
  • Lesnefsky EJ, Gudz TI, Moghaddas S, et al. Aging decreases electron transport complex III activity in heart interfibrillar mitochondria by alteration of the cytochrome c binding site. J Mol Cell Cardiol. 2001;33:37–47. doi:10.1006/jmcc.2000.1273
  • Miwa S, Kashyap S, Chini E, et al. Mitochondrial dysfunction in cell senescence and aging. J Clin Invest. 2022;132:e158447. doi:10.1172/JCI158447
  • Boengler K, Kosiol M, Mayr M, et al. Mitochondria and ageing: role in heart,: skeletal muscle and adipose tissue. J Cachexia Sarcopenia Muscle. 2017;8:349–369. doi:10.1002/jcsm.12178
  • Miwa S, Jow H, Baty K, et al. Low abundance of the matrix arm of complex I in mitochondria predicts longevity in mice. Nat Commun. 2014;5:3837–3837. doi:10.1038/ncomms4837
  • Espinoza SE, Guo H, Fedarko N, et al. Glutathione peroxidase enzyme activity in aging. J Gerontol A Biol Sci Med Sci. 2008;63:505–509. doi:10.1093/gerona/63.5.505
  • Aigner T, Fundel K, Saas J, et al. Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis. Arthritis Rheum. 2006;54:3533–3544. doi:10.1002/art.22174
  • Ruiz-Romero C, Calamia V, Mateos J, et al. Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance. Mol Cell Proteomics MCP. 2008;8:172–189. doi:10.1074/mcp.M800292-MCP200
  • Scott JL, Gabrielides C, Davidson RK, et al. Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease. Ann Rheum Dis. 2010;69:1502–1510. doi:10.1136/ard.2009.119966
  • Nissanka N, Moraes CT. Mitochondrial DNA damage and reactive oxygen species in neurodegenerative disease. FEBS Lett. 2018;592:728–742. doi:10.1002/1873-3468.12956
  • Bota DA, Davies KJA. Mitochondrial Lon protease in human disease and aging: including an etiologic classification of Lon-related diseases and disorders. Free Radic Biol Med. 2016;100:188–198. doi:10.1016/j.freeradbiomed.2016.06.031
  • Ahola S, Langer T, Macvicar T, et al. Mitochondrial proteolysis and metabolic control. Cold Spring Harb Perspect Biol. 2019;11:a033936–a033936. doi:10.1101/cshperspect.a033936
  • Sebastián D, Sorianello E, Segalés J, et al. Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway. EMBO J. 2016;35:1677–1693. doi:10.15252/embj.201593084
  • Chun SK, Lee S, Flores-Toro J, et al. Loss of sirtuin 1 and mitofusin 2 contributes to enhanced ischemia/reperfusion injury in aged livers. Aging Cell. 2018;17:e12761–e12761. doi:10.1111/acel.12761
  • Medala VK, Gollapelli B, Dewanjee S, et al. Mitochondrial dysfunction,: mitophagy, and role of dynamin-related protein 1 in Alzheimer’s disease. J Neurosci Res. 2021;99:1120–1135. doi:10.1002/jnr.24781
  • Alexeyev MF. Is there more to aging than mitochondrial DNA and reactive oxygen species? FEBS J. 2009;276:5768–5787. doi:10.1111/j.1742-4658.2009.07269.x
  • Wolf AM. MtDNA mutations and aging—not a closed case after all? Signal Transduct Target Ther. 2021;6.56.
  • Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell. 2006;127:1109–1122. doi:10.1016/j.cell.2006.11.013
  • Lira VA, Benton CR, Yan Z, et al. PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity. Am J Physiol - Endocrinol Metab. 2010;299.E145-61.
  • Joseph AM, Hood DA. Relationships between exercise, mitochondrial biogenesis and type 2 diabetes. Diabetes Phys Act. 2014;60:48–61.
  • Hou CY, Tain YL, Yu HR, et al. The effects of resveratrol in the treatment of metabolic syndrome. Int J Mol Sci. 2019;20:535. doi:10.3390/ijms20030535
  • Rodop BB, Erbaş O. Mitochondrial dysfunction in aging and disease: the role of nutrition. 2023. Available from: https://www.researchgate.net/publication/371071283.
  • Das SK, Vasudevan DM. Alcohol-induced oxidative stress. Life Sci. 2007;81:177–187. doi:10.1016/j.lfs.2007.05.005
  • Horinouchi T, Higashi T, Mazaki Y, et al. Carbonyl compounds in the gas phase of cigarette mainstream smoke and their pharmacological properties. Biol Pharm Bull. 2016;39:909–914. doi:10.1248/bpb.b16-00025
  • Goel R, Bitzer Z, Reilly SM, et al. Variation in free radical yields from U.S. marketed cigarettes. Chem Res Toxicol. 2017;30:1038–1045. doi:10.1021/acs.chemrestox.6b00359
  • Sánchez-Rodríguez MA, Zacarías-Flores M, Correa-Muñoz E, et al. Oxidative stress risk is increased with a sedentary lifestyle during aging in Mexican women. Oxid Med Cell Longev. 2021;2021:9971765–9971765. doi:10.1155/2021/9971765
  • Calabrese V, Cornelius C, Mancuso C, et al. Cellular stress response: a novel target for chemoprevention and nutritional neuroprotection in aging, neurodegenerative disorders and longevity. Neurochem Res. 2008;33:2444–2471. doi:10.1007/s11064-008-9775-9
  • Calabrese V, Cornelius C, Dinkova-Kostova AT, et al. Vitagenes,: cellular stress response, and acetylcarnitine: relevance to hormesis. BioFactors Oxf Engl. 2009;35:146–160. doi:10.1002/biof.22
  • Son TG, Camandola S, Mattson MP. Hormetic dietary phytochemicals. Neuromolecular Med. 2008;10:236–246. doi:10.1007/s12017-008-8037-y
  • Calabrese EJ. Another California milestone: the first application of Hormesis in litigation and regulation. Int J Toxicol. 2008;27:31–33. doi:10.1080/10915810701876554
  • Iqbal AM, Jamal SF. Essential Hypertension. Treasure Island (FL): StatPearls Publishing; 2023; [cited 2023 Jun 14]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK539859/.
  • Muntner P, Carey RM, Gidding S, et al. Potential US population impact of the 2017 ACC/AHA high blood pressure guideline. Circulation. 2018;137:109–118. doi:10.1161/CIRCULATIONAHA.117.032582
  • Whelton PK, Carey RM, Aronow WS, et al. ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:1269–1324. doi:10.1161/HYP.0000000000000066
  • World Health Organization. Hypertension [Internet]. 2023. Available from: https://www.who.int/news-room/fact-sheets/detail/hypertension.
  • Franco C, Sciatti E, Favero G, et al. Essential hypertension and oxidative stress: novel future perspectives. Int J Mol Sci. 2022;23(22):14489. Available from: /pmc/articles/PMC9692622/.
  • do Vale GT, Tirapelli CR. Are reactive oxygen species important mediators of vascular dysfunction? Curr Hypertens Rev. 2020;16:163–165. doi:10.2174/15734021OTgxdMTQaTcVY
  • Pan Y, Qiao QY, Pan LH, et al. Losartan reduces insulin resistance by inhibiting oxidative stress and enhancing insulin signaling transduction. Exp Clin Endocrinol Diabetes Off J Ger Soc Endocrinol Ger Diabetes Assoc. 2015;123:170–177.
  • Rivasi G, Rafanelli M, Mossello E, et al. Drug-related orthostatic hypotension: beyond anti-hypertensive medications. Drugs Aging. 2020;37:725–738. doi:10.1007/s40266-020-00796-5
  • Lapi F, Azoulay L, Yin H, et al. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study. Br Med J. 2013;346:e8525. doi:10.1136/bmj.e8525
  • Morris EJ, Brown JD, Manini TM, et al. Differences in health-related quality of life among adults with a potential dihydropyridine calcium channel blocker-loop diuretic prescribing cascade. Drugs Aging. 2021;38:625–632. doi:10.1007/s40266-021-00868-0
  • Scheltens P, De Strooper B, Kivipelto M, et al. Alzheimer’s disease. Lancet Lond Engl. 2021;397:1577–1577. doi:10.1016/S0140-6736(20)32205-4
  • Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimers Dement J Alzheimers Assoc. 2022;18:700–789. doi:10.1002/alz.12638
  • Andreone BJ, Lacoste B, Gu C. Neuronal and vascular interactions. Annu Rev Neurosci. 2015;38:25–46. doi:10.1146/annurev-neuro-071714-033835
  • Yoon JH, Seo Y, Jo YS, et al. Brain lipidomics: from functional landscape to clinical significance. Sci Adv. 2022;8:eadc9317. doi:10.1126/sciadv.adc9317
  • Cutler RG, Kelly J, Storie K, et al. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer’s disease. Proc Natl Acad Sci U S A. 2004;101:2070–2070. doi:10.1073/pnas.0305799101
  • Shoeb M, Ansari NH, Srivastava SK, et al. 4-hydroxynonenal in the pathogenesis and progression of human diseases. Curr Med Chem. 2014;21:230–230. doi:10.2174/09298673113209990181
  • Singh M, Dang TN, Arseneault M, et al. Role of by-products of lipid oxidation in Alzheimer’s disease brain: a focus on acrolein. J Alzheimers Dis JAD. 2010;21:741–756. doi:10.3233/JAD-2010-100405
  • Zhao Y, Zhao B. Oxidative stress and the pathogenesis of Alzheimer’s disease. Oxid Med Cell Longev. 2013:316523. Available from: /pmc/articles/PMC3745981/
  • Butterfield DA, Kanski J. Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mech Ageing Dev. 2001;122:945–962. doi:10.1016/S0047-6374(01)00249-4
  • Ahmed N, Ahmed U, Thornalley PJ, et al. Protein glycation: oxidation and nitration adduct residues and free adducts of cerebrospinal fluid in Alzheimer’s disease and link to cognitive impairment. J Neurochem. 2005;92:255–263. doi:10.1111/j.1471-4159.2004.02864.x
  • Al-Hilaly YK, Williams TL, Stewart-Parker M, et al. A central role for dityrosine crosslinking of amyloid-β in Alzheimer’s disease. Acta Neuropathol Commun. 2013;1:83. doi:10.1186/2051-5960-1-83
  • La Penna G, Hureau C, Andreussi O, et al. Identifying: by first-principles simulations, Cu[amyloid-β] species making Fenton-type reactions in Alzheimer’s disease. J Phys Chem B. 2013;117:16455–16467. doi:10.1021/jp410046w
  • Chen K, Jiang X, Wu M, et al. Ferroptosis, a potential therapeutic target in Alzheimer’s disease. Front Cell Dev Biol. 2021;9:704298. Available from: https://pubmed-ncbi-nlm-nih-gov.uchile.idm.oclc.org/34422824/.
  • Calabrese V, Mancuso C, Calvani M, et al. Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat Rev Neurosci. 2007;8:766–775. doi:10.1038/nrn2214
  • Picón-Pagès P, Garcia-Buendia J, Muñoz FJ. Functions and dysfunctions of nitric oxide in brain. Biochim Biophys Acta Mol Basis Dis. 2019;1865:1949–1967. doi:10.1016/j.bbadis.2018.11.007
  • Chachlaki K, Prevot V. Nitric oxide signalling in the brain and its control of bodily functions. Br J Pharmacol. 2020;177:5437–5458. doi:10.1111/bph.14800
  • Pomilio AB, Vitale AA, Lazarowski AJ. COVID-19 and Alzheimer’s disease: neuroinflammation: oxidative stress, ferroptosis, and mechanisms involved. Curr Med Chem. 2023;30(35):3993–4031.
  • Phillips MI, de Oliveira EM. Brain renin angiotensin in disease. J Mol Med Berl Ger. 2008;86:715–722. doi:10.1007/s00109-008-0331-5
  • Ababei D-C, Bild V, Macadan I, et al. Therapeutic implications of renin-angiotensin system modulators in Alzheimer’s dementia. Pharmaceutics. 2023;15:2290. doi:10.3390/pharmaceutics15092290
  • Hu W, Li Y, Zhao Y, et al. Telmisartan and Rosuvastatin synergistically ameliorate dementia and cognitive impairment in older hypertensive patients with apolipoprotein E genotype. Front Aging Neurosci. 2020;12:154. doi:10.3389/fnagi.2020.00154
  • Liu C-H, Sung P-S, Li Y-R, et al. Telmisartan use and risk of dementia in type 2 diabetes patients with hypertension: a population-based cohort study. PLoS Med. 2021;18:e1003707. doi:10.1371/journal.pmed.1003707
  • Sharma K. Cholinesterase inhibitors as Alzheimer’s therapeutics (Review). Mol Med Rep. 2019;20:1479–1487.
  • Sangaleti CT, Katayama KY, De Angelis K, et al. The cholinergic drug galantamine alleviates oxidative stress alongside anti-inflammatory and cardio-metabolic effects in subjects with the metabolic syndrome in a randomized trial. Front Immunol. 2021;12:613979. doi:10.3389/fimmu.2021.613979
  • Kundo NK, Manik MIN, Biswas K, et al. Identification of polyphenolics from Loranthus globosus as potential inhibitors of cholinesterase and oxidative stress for Alzheimer’s disease treatment. BioMed Res Int. 2021:9154406.
  • Althobaiti YS. Development of memantine as a drug for Alzheimer’s disease: a review of preclinical and clinical studies. Trop J Pharm Res. 2020;19:1535–1540. doi:10.4314/tjpr.v19i7.28
  • Matsunaga S, Kishi T, Nomura I, et al. The efficacy and safety of memantine for the treatment of Alzheimer’s disease. Expert Opin Drug Saf. 2018;17:1053–1061. doi:10.1080/14740338.2018.1524870
  • Guo J, Wang Z, Liu R, et al. Memantine, donepezil, or combination therapy-what is the best therapy for Alzheimer’s disease? A network meta-analysis. Brain Behav. 2020;10(11):e01831.
  • Press D, Buss S. Treatment of Alzheimer disease. Cholinesterase Inhib Treat Dement. 2021. Available from: https://www.uptodate.com/contents/treatment-of-alzheimer-disease
  • Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet Lond Engl. 2020;396:413–446. doi:10.1016/S0140-6736(20)30367-6
  • Allen KD, Thoma LM, Golightly YM. Epidemiology of osteoarthritis. Osteoarthritis Cartilage. 2022;30:184–195. doi:10.1016/j.joca.2021.04.020
  • Johnson VL, Hunter DJ. The epidemiology of osteoarthritis. Best Pract Res Clin Rheumatol. 2014;28:5–15. doi:10.1016/j.berh.2014.01.004
  • Hawker GA, King LK. The burden of osteoarthritis in older adults. Clin Geriatr Med. 2022;38:181–192. doi:10.1016/j.cger.2021.11.005
  • Coryell PR, Diekman BO, Loeser RF. Mechanisms and therapeutic implications of cellular senescence in osteoarthritis. Nat Rev Rheumatol. 2021;17:47–57. doi:10.1038/s41584-020-00533-7
  • Franceschi C, Garagnani P, Parini P, et al. Inflammaging: a new immune–metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018;14:576–590. doi:10.1038/s41574-018-0059-4
  • Jeon OH, David N, Campisi J, et al. Senescent cells and osteoarthritis: a painful connection. J Clin Invest. 2018;128:1229–1237. doi:10.1172/JCI95147
  • Delmonico MJ, Harris TB, Visser M, et al. Longitudinal study of muscle strength, quality, and adipose tissue infiltration. Am J Clin Nutr. 2009;90:1579–1579. doi:10.3945/ajcn.2009.28047
  • Sellam J, Berenbaum F. Is osteoarthritis a metabolic disease? Joint Bone Spine. 2013;80:568–573. doi:10.1016/j.jbspin.2013.09.007
  • Courties A, Gualillo O, Berenbaum F, et al. Metabolic stress-induced joint inflammation and osteoarthritis. Osteoarthritis Cartilage. 2015;23:1955–1965. doi:10.1016/j.joca.2015.05.016
  • Loeser RF, Collins JA, Diekman BO. Ageing and the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016;12:412–412. doi:10.1038/nrrheum.2016.65
  • Gossan N, Zeef L, Hensman J, et al. The circadian clock in murine chondrocytes regulates genes controlling key aspects of cartilage homeostasis. Arthritis Rheum. 2013;65:2334–2345. doi:10.1002/art.38035
  • Jones DP. Redox theory of aging. Redox Biol. 2015;5:71–71. doi:10.1016/j.redox.2015.03.004
  • Nemoto S, Finkel T. Redox regulation of forkhead proteins through a p66shc-dependent signaling pathway. Science. 2002;295:2450–2452. doi:10.1126/science.1069004
  • Mazumder S, De R, Debsharma S, et al. Indomethacin impairs mitochondrial dynamics by activating the PKCζ-p38-DRP1 pathway and inducing apoptosis in gastric cancer and normal mucosal cells. J Biol Chem. 2019;294:8238–8258. doi:10.1074/jbc.RA118.004415
  • Mazumder S, De R, Sarkar S, et al. Selective scavenging of intra-mitochondrial superoxide corrects diclofenac-induced mitochondrial dysfunction and gastric injury: a novel gastroprotective mechanism independent of gastric acid suppression. Biochem Pharmacol. 2016;121:33–51. doi:10.1016/j.bcp.2016.09.027
  • Koike M, Nojiri H, Ozawa Y, et al. Mechanical overloading causes mitochondrial superoxide and SOD2 imbalance in chondrocytes resulting in cartilage degeneration. Sci Rep. 2015;5:11722.
  • Hanachi N, Charef N, Baghiani A, et al. Comparison of xanthine oxidase levels in synovial fluid from patients with rheumatoid arthritis and other joint inflammations. Saudi Med J. 2009;30:1422–1425.
  • Yin W, Park JI, Loeser RF. Oxidative stress inhibits insulin-like growth factor-I induction of chondrocyte proteoglycan synthesis through differential regulation of phosphatidylinositol 3-Kinase-Akt and MEK-ERK MAPK signaling pathways. J Biol Chem. 2009;284:31972–31981. doi:10.1074/jbc.M109.056838
  • Wood ST, Long DL, Reisz JA, et al. Cysteine-mediated redox regulation of cell signaling in chondrocytes stimulated with fibronectin fragments. Arthritis Rheumatol Hoboken NJ. 2016;68:117–126. doi:10.1002/art.39326
  • Collins JA, Wood ST, Nelson KJ, et al. Oxidative stress promotes peroxiredoxin hyperoxidation and attenuates pro-survival signaling in aging chondrocytes. J Biol Chem. 2016;291:6641–6654. doi:10.1074/jbc.M115.693523
  • Miao Y, Chen Y, Xue F, et al. Contribution of ferroptosis and GPX4’s dual functions to osteoarthritis progression. EBioMedicine. 2022;76:103847 doi:10.1016/j.ebiom.2022.103847.
  • Bennell KL, Hunter DJ, Hinman RS. Management of osteoarthritis of the knee. Br Med J. 2012;345:e493410.1136/bmj.e4934.
  • McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014;22:363–388. doi:10.1016/j.joca.2014.01.003
  • Kompel AJ, Roemer FW, Murakami AM, et al. Intra-articular corticosteroid injections in the hip and knee: perhaps not as safe as we thought? Radiology. 2019;293:656–663. doi:10.1148/radiol.2019190341
  • Sandoval-Acuña C, Lopez-Alarcón C, Aliaga ME, et al. Inhibition of mitochondrial complex I by various non-steroidal anti-inflammatory drugs and its protection by quercetin via a coenzyme Q-like action. Chem Biol Interact. 2012;199:18–28. doi:10.1016/j.cbi.2012.05.006
  • Shin SJ, Noh CK, Lim SG, et al. Non-steroidal anti-inflammatory drug-induced enteropathy. Intest Res. 2017;15:446–455. doi:10.5217/ir.2017.15.4.446
  • Watanabe T, Fujiwara Y, Chan FKL. Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: a comprehensive review. J Gastroenterol. 2020;55:481–495. doi:10.1007/s00535-019-01657-8
  • Baigent C, Bhala N, Emberson J, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet Lond Engl. 2013;382:769–779. doi:10.1016/S0140-6736(13)60900-9
  • Huerta C, Castellsague J, Varas-Lorenzo C, et al. Nonsteroidal anti-inflammatory drugs and risk of ARF in the general population. Am J Kidney Dis. 2005;45:531–539. doi:10.1053/j.ajkd.2004.12.005
  • Ory MG, Anderson LA, Friedman DB, et al. Cancer prevention among adults aged 45-64 years: setting the stage. Am J Prev Med. 2014;46:(3 Suppl 1):S1–6. doi:10.1016/j.amepre.2013.10.027.
  • Pilleron S, Sarfati D, Janssen-Heijnen M, et al. Global cancer incidence in older adults, 2012 and 2035: a population-based study. Int J Cancer. 2019;144:49–58. doi:10.1002/ijc.31664
  • Novak J, Goldberg A, Dharmarajan K, et al. Polypharmacy in older adults with cancer undergoing radiotherapy: a review. J Geriatr Oncol. 2022;13:778–778. doi:10.1016/j.jgo.2022.02.007
  • Zabłocka-Słowińska K, Płaczkowska S, Skórska K, et al. Oxidative stress in lung cancer patients is associated with altered serum markers of lipid metabolism. PLoS One. 2019;14:e0215246. doi:10.1371/journal.pone.0215246
  • Desouki MM, Kulawiec M, Bansal S, et al. Cross talk between mitochondria and superoxide generating NADPH oxidase in breast and ovarian tumors. Cancer Biol Ther. 2005;4:1367–1373. doi:10.4161/cbt.4.12.2233
  • Kawahara T, Kohjima M, Kuwano Y, et al. Helicobacter pylori lipopolysaccharide activates Rac1 and transcription of NADPH oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells. Am J Physiol - Cell Physiol. 2005;288(2):C450–7. doi:10.1152/ajpcell.00319.2004.
  • Fukuyama M, Rokutan K, Sano T, et al. Overexpression of a novel superoxide-producing enzyme, NADPH oxidase 1, in adenoma and well differentiated adenocarcinoma of the human colon. Cancer Lett. 2005;221:97–104. doi:10.1016/j.canlet.2004.08.031
  • Block K, Gorin Y, New DD, et al. The NADPH oxidase subunit p22phox inhibits the function of the tumor suppressor protein tuberin. Am J Pathol. 2010;176:2447–2455. doi:10.2353/ajpath.2010.090606
  • Shimada K, Fujii T, Anai S, et al. ROS generation via NOX4 and its utility in the cytological diagnosis of urothelial carcinoma of the urinary bladder. BMC Urol. 2011;11:1–12. doi:10.1186/1471-2490-11-1
  • Jitschin R, Hofmann AD, Bruns H, et al. Mitochondrial metabolism contributes to oxidative stress and reveals therapeutic targets in chronic lymphocytic leukemia. Blood. 2014;123:2663–2672. doi:10.1182/blood-2013-10-532200
  • Hart PC, Mao M, De Abreu ALP, et al. MnSOD upregulation sustains the Warburg effect via mitochondrial ROS and AMPK-dependent signalling in cancer. Nat Commun. 2015;6:6053.
  • Foo BJ-A, Eu JQ, Hirpara JL, et al. Interplay between mitochondrial metabolism and cellular redox state dictates cancer cell survival. Oxid Med Cell Longev. 2021;2021:1341604.
  • Burdick AD, Davis JW, Liu KJ, et al. Benzo(a)pyrene quinones increase cell proliferation, generate reactive oxygen species, and transactivate the epidermal growth factor receptor in breast epithelial cells. Cancer Res. 2003;63:7825–7833.
  • Sarsour EH, Venkataraman S, Kalen AL, et al. Manganese superoxide dismutase activity regulates transitions between quiescent and proliferative growth. Aging Cell. 2008;7:405–417. doi:10.1111/j.1474-9726.2008.00384.x
  • Sieber OM, Heinimann K, Tomlinson IPM. Genomic instability - the engine of tumorigenesis? Nat Rev Cancer. 2003;3:701–708. doi:10.1038/nrc1170
  • Cooke MS, Evans MD, Dizdaroglu M, et al. Oxidative DNA damage: mechanisms: mutation, and disease. FASEB J. 2003;17:1195–1214. doi:10.1096/fj.02-0752rev
  • Moeller BJ, Cao Y, Li CY, et al. Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation: free radicals, and stress granules. Cancer Cell. 2004;5:429–441. doi:10.1016/S1535-6108(04)00115-1
  • Xu RH, Pelicano H, Zhou Y, et al. Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res. 2005;65:613–621. doi:10.1158/0008-5472.613.65.2
  • Yoo NJ, Kim HR, Kim YR, et al. Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology. 2012;60:943–952. doi:10.1111/j.1365-2559.2012.04178.x
  • Sajadimajd S, Khazaei M. Oxidative stress and cancer: the role of Nrf2. Curr Cancer Drug Targets. 2018;18:538–557. doi:10.2174/1568009617666171002144228
  • Crociani O, Marzi I, Cipolleschi MG, et al. The unveiling of the Warburg effect and the inscribed innovative approach to a radical non toxic anticancer therapy. Cell Cycle Georget Tex. 2018;17:288–297. doi:10.1080/15384101.2017.1403679
  • Schiliro C, Firestein BL. Mechanisms of metabolic reprogramming in cancer cells supporting enhanced growth and proliferation. Cells. 2021;10:1056. doi:10.3390/cells10051056
  • Chen H, Yan Z, Wu S, et al. A glutathione-responsive polyphenol - constructed nanodevice for double roles in apoptosis and ferroptosis. Colloids Surf B Biointerfaces. 2021;205:111902. doi:10.1016/j.colsurfb.2021.111902
  • Ghigo A, Li M, Hirsch E. New signal transduction paradigms in anthracycline-induced cardiotoxicity. Biochim Biophys Acta BBA - Mol Cell Res. 2016;1863:1916–1925. doi:10.1016/j.bbamcr.2016.01.021
  • Stephens C, Andrade RJ, Lucena MI. Mechanisms of drug-induced liver injury. Curr Opin Allergy Clin Immunol. 2014;14:286–292. doi:10.1097/ACI.0000000000000070
  • Baumgart SJ, Haendler B. Drug-induced liver injury: cascade of events leading to cell death, apoptosis or necrosis. Int J Mol Sci. 2017;18:E1018–E1018. doi:10.3390/ijms18051017
  • Staff NP, Grisold A, Grisold W, et al. Chemotherapy-induced peripheral neuropathy: a current review. Ann Neurol. 2017;81:772–781. doi:10.1002/ana.24951
  • Ren X, Keeney JTR, Miriyala S, et al. The triangle of death of neurons: oxidative damage, mitochondrial dysfunction, and loss of choline-containing biomolecules in brains of mice treated with doxorubicin. Advanced insights into mechanisms of chemotherapy induced cognitive impairment (“chemobrain”) involving TNF-α. Free Radic Biol Med. 2018;134:1–8. doi:10.1016/j.freeradbiomed.2018.12.029
  • Herrmann J. Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia. Nat Rev Cardiol. 2020;17:474–502. doi:10.1038/s41569-020-0348-1
  • McElroy T, Allen AR. A bibliometric review of publications on oxidative stress and chemobrain: 1990-2019. Antioxid Basel Switz. 2020;9:E439–E439. doi:10.3390/antiox9050439
  • Man Q, Deng Y, Li P, et al. Licorice ameliorates cisplatin-induced hepatotoxicity through antiapoptosis, antioxidative stress, anti-inflammation, and acceleration of metabolism. Front Pharmacol. 2020;11:563750–563750. doi:10.3389/fphar.2020.563750
  • Fabiani I, Aimo A, Grigoratos C, et al. Oxidative stress and inflammation: determinants of anthracycline cardiotoxicity and possible therapeutic targets. Heart Fail Rev. 2020;26:881–890. doi:10.1007/s10741-020-10063-9
  • Pantazi D, Tselepis AD. Cardiovascular toxic effects of antitumor agents: pathogenetic mechanisms. Thromb Res. 2022;213:S95–102. doi:10.1016/j.thromres.2021.12.017
  • Li G, Ding K, Qiao Y, et al. Flavonoids regulate inflammation and oxidative stress in cancer. Molecules. 2020;25(23):5628. Available from: /pmc/articles/PMC7729519/.
  • Lee SG, Kim B, Yang Y, et al. Berry anthocyanins suppress the expression and secretion of proinflammatory mediators in macrophages by inhibiting nuclear translocation of NF-κB independent of NRF2-mediated mechanism. J Nutr Biochem. 2014;25:404–411. doi:10.1016/j.jnutbio.2013.12.001
  • Edirisinghe I, Banaszewski K, Cappozzo J, et al. Effect of black currant anthocyanins on the activation of endothelial nitric oxide synthase (eNOS) in vitro in human endothelial cells. J Agric Food Chem. 2011;59:8616–8624. doi:10.1021/jf201116y
  • World Health Organization. Obesity [Internet]. Available from: https://www.who.int/health-topics/obesity#tab = tab_1.
  • Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism. 2019;92:6–10. doi:10.1016/j.metabol.2018.09.005
  • Colleluori G, Villareal DT. Aging: obesity, sarcopenia and the effect of diet and exercise intervention. Exp Gerontol. 2021;155:111561. doi:10.1016/j.exger.2021.111561
  • Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48:16–31. doi:10.1093/ageing/afy169
  • Le Lay S, Simard G, Martinez MC, et al. Oxidative stress and metabolic pathologies: from an adipocentric point of view. Oxid Med Cell Longev. 2014;2014:908539. Available from: /pmc/articles/PMC4131099/.
  • Khalil A, Berrougui H. Mechanism of action of resveratrol in lipid metabolism and atherosclerosis. Clin. Lipidol. 2017;4:527–531. doi:10.2217/clp.09.53
  • Meneses MJ, Silvestre R, Sousa-Lima I, et al. Paraoxonase-1 as a regulator of glucose and lipid homeostasis: impact on the onset and progression of metabolic disorders. Int J Mol Sci. 2019;20. doi:10.3390/ijms20164049
  • Hansel B, Giral P, Nobecourt E, et al. Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity. J Clin Endocrinol Metab. 2004;89:4963–4971. doi:10.1210/jc.2004-0305
  • Holvoet P. Relations between metabolic syndrome: oxidative stress and inflammation and cardiovascular disease. Verh K Acad Geneeskd Belg. 2008;70:193–219.
  • Maingrette F, Renier G. Leptin increases lipoprotein lipase secretion by macrophages: involvement of oxidative stress and protein kinase C. Diabetes. 2003;52:2121–2128. doi:10.2337/diabetes.52.8.2121
  • Chang C-C, Sia K-C, Chang J-F, et al. Participation of lipopolysaccharide in hyperplasic adipose expansion: involvement of NADPH oxidase/ROS/p42/p44 MAPK-dependent Cyclooxygenase-2. J Cell Mol Med. 2022;26:3850–3861. doi:10.1111/jcmm.17419
  • Silvester AJ, Aseer KR, Yun JW. Dietary polyphenols and their roles in fat browning. J Nutr Biochem. 2019;64:1–12. doi:10.1016/j.jnutbio.2018.09.028
  • Qiu H, Schlegel V. Impact of nutrient overload on metabolic homeostasis. Nutr Rev. 2018;76:693–707. doi:10.1093/nutrit/nuy023
  • Bhatti JS, Bhatti GK, Reddy PH. Mitochondrial dysfunction and oxidative stress in metabolic disorders - a step towards mitochondria based therapeutic strategies. Biochim Biophys Acta Mol Basis Dis. 2017;1863:1066–1077. doi:10.1016/j.bbadis.2016.11.010
  • Bouchez C, Devin A. Mitochondrial biogenesis and mitochondrial reactive oxygen species (ROS): a complex relationship regulated by the cAMP/PKA signaling pathway. Cells. 2019;8:287. doi:10.3390/cells8040287
  • Mulero MC, Huxford T, Ghosh G. NF-κB, IκB, and IKK: integral components of immune system signaling. Adv Exp Med Biol. 2019;1172:207–226. doi:10.1007/978-981-13-9367-9_10
  • Oliveira-Marques V, Marinho HS, Cyrne L, et al. Role of hydrogen peroxide in NF-kappaB activation: from inducer to modulator. Antioxid Redox Signal. 2009;11:2223–2243. doi:10.1089/ars.2009.2601
  • Martínez-Martínez E, Jurado-López R, Valero-Muñoz M, et al. Leptin induces cardiac fibrosis through galectin-3, mTOR and oxidative stress: potential role in obesity. J Hypertens. 2014;32:1104–1114. discussion 1114. doi:10.1097/HJH.0000000000000149
  • Xu X, Huang X, Zhang L, et al. Adiponectin protects obesity-related glomerulopathy by inhibiting ROS/NF-κB/NLRP3 inflammation pathway. BMC Nephrol. 2021;22(1):218. doi:10.1186/s12882-021-02391-1.
  • Mitrou P, Boutati E, Lambadiari V, et al. Insulin resistance in hyperthyroidism: the role of IL6 and TNF alpha. Eur J Endocrinol. 2010;162:121–126. doi:10.1530/EJE-09-0622
  • Bjørklund G, Peana M, Pivina L, et al. Iron deficiency in obesity and after bariatric surgery. Biomolecules. 2021;11(5):613. doi:10.3390/biom11050613.
  • González-Domínguez Á, Visiedo-García FM, Domínguez-Riscart J, et al. Iron metabolism in obesity and metabolic syndrome. Int J Mol Sci. 2020;21:5529. doi:10.3390/ijms21155529
  • Sombra LRS, Anastasopoulou C Pharmacologic Therapy for Obesity. [Updated 2022 Aug 29] In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Available from: https://www-ncbi-nlm-nih-gov.uchile.idm.oclc.org/books/NBK562269/.
  • Kawanami D, Takashi Y. GLP-1 receptor agonists in diabetic kidney disease: from clinical outcomes to mechanisms. Front Pharmacol. 2020;11:967. doi:10.3389/fphar.2020.00967
  • Mehdi SF, Pusapati S, Anwar MS, et al. Glucagon-like peptide-1: a multi-faceted anti-inflammatory agent. Front Immunol. 2023;14:1148209. doi:10.3389/fimmu.2023.1148209
  • Hayes JD, Dinkova-Kostova AT. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci. 2014;39:199–218. doi:10.1016/j.tibs.2014.02.002
  • Dinkova-Kostova AT, Abramov AY. The emerging role of Nrf2 in mitochondrial function. Free Radic Biol Med. 2015;88:179–188. doi:10.1016/j.freeradbiomed.2015.04.036
  • Mangmool S, Hemplueksa P, Parichatikanond W, et al. Epac is required for GLP-1R-mediated inhibition of oxidative stress and apoptosis in cardiomyocytes. Mol Endocrinol Baltim Md. 2015;29:583–596. doi:10.1210/me.2014-1346
  • Fernández-Millán E, Martín MA, Goya L, et al. Glucagon-like peptide-1 improves beta-cell antioxidant capacity via extracellular regulated kinases pathway and Nrf2 translocation. Free Radic Biol Med. 2016;95:16–26. doi:10.1016/j.freeradbiomed.2016.03.002
  • Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics-2022 update: a report from the American Heart Association. Circulation. 2022;145:E153–E639.
  • Kattoor AJ, Pothineni NVK, Palagiri D, et al. Oxidative stress in atherosclerosis. Curr Atheroscler Rep. 2017;19:42. doi:10.1007/s11883-017-0678-6
  • Ford TJ, Corcoran D, Berry C. Stable coronary syndromes: pathophysiology: diagnostic advances and therapeutic need. Heart Br Card Soc. 2018;104:284–292.
  • King TC. Cell injury, cellular responses to injury, and cell death. Elseviers Integr Pathol. 2007: 1–20.
  • Sanada S, Komuro I, Kitakaze M. Pathophysiology of myocardial reperfusion injury: preconditioning,: postconditioning, and translational aspects of protective measures. Am J Physiol Heart Circ Physiol. 2011;301. doi:10.1152/ajpheart.00553.2011
  • Kalogeris T, Baines CP, Krenz M, et al. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol. 2012;298:229–229. doi:10.1016/B978-0-12-394309-5.00006-7
  • Yellon DM, Hausenloy DJ. Myocardial reperfusion injury [Internet]. Massachusetts Medical Society; 2007 [cited 2023 May 1]. Available from: https://www.nejm.org/doi/pdf/10.1056NEJMra071667.
  • Algoet M, Janssens S, Himmelreich U, et al. Myocardial ischemia-reperfusion injury and the influence of inflammation. Trends Cardiovasc Med. 2023;33:357–366. doi:10.1016/j.tcm.2022.02.005
  • Suski JM, Lebiedzinska M, Bonora M, et al. Relation between mitochondrial membrane potential and ROS formation. Methods Mol Biol Clifton NJ. 2012;810:183–205. doi:10.1007/978-1-61779-382-0_12
  • Wu MY, Yiang GT, Liao WT, et al. Current mechanistic concepts in ischemia and reperfusion injury. Cell Physiol Biochem. 2018;46:1650–1667. doi:10.1159/000489241
  • Neri M, Fineschi V, Paolo M, et al. Cardiac oxidative stress and inflammatory cytokines response after myocardial infarction. Curr Vasc Pharmacol. 2015;13:26–36. doi:10.2174/15701611113119990003
  • Zhao ZQ, Nakamura M, Wang NP, et al. Dynamic progression of contractile and endothelial dysfunction and infarct extension in the late phase of reperfusion. J Surg Res. 2000;94:133–144. doi:10.1006/jsre.2000.6029
  • Incalza MA, D’Oria R, Natalicchio A, et al. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascul Pharmacol. 2018;100:1–19. doi:10.1016/j.vph.2017.05.005
  • Luo S, Lei H, Qin H, et al. Molecular mechanisms of endothelial NO synthase uncoupling. Curr Pharm Des. 2014;20:3548–3553. doi:10.2174/13816128113196660746
  • Garrido AM, Griendling KK. NADPH oxidases and angiotensin II receptor signaling. Mol Cell Endocrinol. 2009;302:148–158. doi:10.1016/j.mce.2008.11.003
  • Tibaut M, Mekis D, Petrovic D. Pathophysiology of myocardial infarction and acute management strategies. Cardiovasc Hematol Agents Med Chem. 2017;14:150–159. doi:10.2174/1871525714666161216100553
  • Sima P, Vannucci L, Vetvicka V. Atherosclerosis as autoimmune disease. Ann Transl Med. 2018;6:116. doi:10.21037/atm.2018.02.02
  • Sato A, Ueda C, Kimura R, et al. Angiotensin II induces the aggregation of native and oxidized low-density lipoprotein. Eur Biophys J EBJ. 2018;47:1–9. doi:10.1007/s00249-017-1208-8
  • Yeh HL, Kuo LT, Sung FC, et al. Association between polymorphisms of antioxidant gene (MnSOD, CAT, and GPx1) and risk of coronary artery disease. BioMed Res Int. 2018;2018:5086869. doi:10.1155/2018/5086869.
  • Förstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res. 2017;120:713–735. doi:10.1161/CIRCRESAHA.116.309326
  • Singh A, Museedi AS, Grossman SA. Acute coronary syndrome. StatPearls [Internet]. 2022; Available from: https://www-ncbi-nlm-nih-gov.uchile.idm.oclc.org/books/NBK459157/.
  • Steinhubl SR. Why have antioxidants failed in clinical trials? Am J Cardiol. 2008;101(10A):14D–19D. doi:10.1016/j.amjcard.2008.02.003.
  • Rodrigo R, Prieto JC, Aguayo R, et al. Joint cardioprotective effect of vitamin C and other antioxidants against reperfusion injury in patients with acute myocardial infarction undergoing percutaneous coronary intervention. Molecules. 2021;26:5702. doi:10.3390/molecules26185702
  • Ahmed S, Ahmed N, Rungatscher A, et al. Cocoa flavonoids reduce inflammation and oxidative stress in a myocardial ischemia-reperfusion experimental model. Antioxid Basel Switz. 2020;9:167. doi:10.3390/antiox9020167
  • ElSayed NA, Aleppo G, Aroda VR, et al. Classification and diagnosis of diabetes: standards of care in diabetes—2023. Diabetes Care. 2022;46:S19–S40. doi:10.2337/dc23-S002
  • International Diabetes Federation. IDF diabetes atlas 2021 | IDF Diabetes Atlas [Internet]. 2022. Available from: https://diabetesatlas.org/atlas/tenth-edition/.
  • Papachristoforou E, Lambadiari V, Maratou E, et al. Association of glycemic indices (hyperglycemia, glucose variability, and hypoglycemia) with oxidative stress and diabetic complications. J Diabetes Res. 2020;2020:7489795. doi:10.1155/2020/7489795.
  • Kang Q, Yang C. Oxidative stress and diabetic retinopathy: molecular mechanisms: pathogenetic role and therapeutic implications. Redox Biol. 2020;37:101799. doi:10.1016/j.redox.2020.101799.
  • Darenskaya MA, Kolesnikova LI, Kolesnikov SI. Oxidative stress: pathogenetic role in diabetes mellitus and its complications and therapeutic approaches to correction. Bull Exp Biol Med. 2021;171:136–149. doi:10.47056/0365-9615-2021-171-2-136-149
  • Kiss L, Szabó C. The pathogenesis of diabetic complications: the role of DNA injury and poly(ADP-ribose) polymerase activation in peroxynitrite-mediated cytotoxicity. Mem Inst Oswaldo Cruz. 2005;100(Suppl 1):29–37. doi:10.1590/S0074-02762005000900007
  • Khalid M, Petroianu G, Adem A. Advanced glycation end products and diabetes mellitus: mechanisms and perspectives. Biomolecules. 2022;12(4):542. doi:10.3390/biom12040542.
  • Baghaie L, Bunsick DA, Szewczuk MR. Insulin receptor signaling in health and disease. Biomolecules. 2023;13:807–807. doi:10.3390/biom13050807
  • Howes KA, Liu Y, Dunaief JL, et al. Receptor for advanced glycation end products and age-related macular degeneration. Invest Ophthalmol Vis Sci. 2004;45:3713–3720. doi:10.1167/iovs.04-0404
  • Moldogazieva NT, Mokhosoev IM, Mel’Nikova TI, et al. Oxidative stress and advanced lipoxidation and glycation end products (ALEs and AGEs) in aging and age-related diseases. Oxid Med Cell Longev. 2019;2019:3085756. doi:10.1155/2019/3085756.
  • Lorenzi M. The polyol pathway as a mechanism for diabetic retinopathy: attractive, elusive, and resilient. Exp Diabetes Res. 2007;2007:61038. doi:10.1155/2007/61038.
  • Cho S-J, Roman G, Yeboah F, et al. The road to advanced glycation end products: a mechanistic perspective. Curr Med Chem. 2007;14:1653–1671. doi:10.2174/092986707780830989
  • Inoguchi T, Li P, Umeda F, et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C–dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes. 2000;49:1939–1945. doi:10.2337/diabetes.49.11.1939
  • Faramoushi M, Amir Sasan R, Sari Sarraf V, et al. Cardiac fibrosis and down regulation of GLUT4 in experimental diabetic cardiomyopathy are ameliorated by chronic exposures to intermittent altitude. J Cardiovasc Thorac Res. 2016;8:26–33. doi:10.15171/jcvtr.2016.05
  • Pacher P, Szabó C. Role of poly(ADP-ribose) polymerase-1 activation in the pathogenesis of diabetic complications: endothelial dysfunction, as a common underlying theme. Antioxid Redox Signal. 2005;7:1568–1580. doi:10.1089/ars.2005.7.1568
  • Halim M, Halim A. The effects of inflammation, aging and oxidative stress on the pathogenesis of diabetes mellitus (type 2 diabetes). Diabetes Metab Syndr Clin Res Rev. 2019;13:1165–1172. doi:10.1016/j.dsx.2019.01.040
  • Luc K, Schramm-Luc A, Guzik TJ, et al. Oxidative stress and inflammatory markers in prediabetes and diabetes. J Physiol Pharmacol Off J Pol Physiol Soc. 2019;70(6):809–824. doi:10.26402/jpp.2019.6.01.
  • Krogh-Madsen R, Møller K, Dela F, et al. Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-alpha, and FFAs to low-dose endotoxemia in humans. Am J Physiol Endocrinol Metab. 2004;286(5):E766–72. doi:10.1152/ajpendo.00468.2003.
  • Akbari M, Hassan-Zadeh V. IL-6 signalling pathways and the development of type 2 diabetes. Inflammopharmacology. 2018;26:685–698. doi:10.1007/s10787-018-0458-0
  • Yaribeygi H, Sathyapalan T, Atkin SL, et al. Molecular mechanisms linking oxidative stress and diabetes mellitus. Oxid Med Cell Longev. 2020;2020:8609213. doi:10.1155/2020/8609213
  • Zhang P, Li T, Wu X, et al. Oxidative stress and diabetes: antioxidative strategies. Front Med. 2020;14:583–600. doi:10.1007/s11684-019-0729-1
  • Fonseca SG, Gromada J, Urano F. Endoplasmic reticulum stress and pancreatic β-cell death. Trends Endocrinol Metab TEM. 2011;22:266–274.
  • Torres-Castro I, Arroyo-Camarena ÚD, Martínez-Reyes CP, et al. Human monocytes and macrophages undergo M1-type inflammatory polarization in response to high levels of glucose. Immunol Lett. 2016;176:81–89. doi:10.1016/j.imlet.2016.06.001
  • Alexopoulos AS, Kahkoska AR, Pate V, et al. Deintensification of treatment with sulfonylurea and insulin after severe hypoglycemia among older adults with diabetes. JAMA Netw Open. 2021;4(11):e2132215. doi:10.1001/jamanetworkopen.2021.32215.
  • Nam YH, Brensinger CM, Bilker WB, et al. Serious hypoglycemia and use of warfarin in combination with sulfonylureas or metformin. Clin Pharmacol Ther. 2019;105:210–218. doi:10.1002/cpt.1146
  • Wang G, Wang Y, Yang Q, et al. Metformin prevents methylglyoxal-induced apoptosis by suppressing oxidative stress in vitro and in vivo. Cell Death Dis. 2022;13(1):29. doi:10.1038/s41419-021-04478-x.
  • Katila N, Bhurtel S, Park PH, et al. Metformin attenuates rotenone-induced oxidative stress and mitochondrial damage via the AKT/Nrf2 pathway. Neurochem Int. 2021;148:105120. doi:10.1016/j.neuint.2021.105120.
  • Zhao X, Liu L, Jiang Y, et al. Protective effect of metformin against hydrogen peroxide-induced oxidative damage in human retinal pigment epithelial (RPE) cells by enhancing autophagy through activation of AMPK pathway. Oxid Med Cell Longev. 2020;2020:2524174. doi:10.1155/2020/2524174.
  • Padki MM, Stambler I. Encycl Gerontol Popul Aging. Targeting Aging with Metformin (TAME). Springer, Cham; 2021. p. 4098–4910. doi:10.1007/978-3-030-22009-9_400.
  • Mohammed I, Hollenberg MD, Ding H, et al. A critical review of the evidence that metformin is a putative anti-aging drug that enhances healthspan and extends lifespan. Front Endocrinol. 2021;12:718942.
  • Apostolova N, Iannantuoni F, Gruevska A, et al. Mechanisms of action of metformin in type 2 diabetes: effects on mitochondria and leukocyte-endothelium interactions. Redox Biol. 2020;34:101517. 10.1016/j.redox.2020.101517.
  • Zenebe Y, Akele B, W/Selassie M, et al. Prevalence and determinants of depression among old age: a systematic review and meta-analysis. Ann Gen Psychiatry. 2021;20:55. doi:10.1186/s12991-021-00375-x
  • Inoue K, Beekley J, Goto A, et al. Depression and cardiovascular disease events among patients with type 2 diabetes: A systematic review and meta-analysis with bias analysis. J Diabetes Complications. 2020;34:107710. doi:10.1016/j.jdiacomp.2020.107710
  • American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder. Arlington (VA): American Psychiatric Association; 2010.
  • Tedeschini E, Levkovitz Y, Iovieno N, et al. Efficacy of antidepressants for late-life depression: a meta-analysis and meta-regression of placebo-controlled randomized trials. J Clin Psychiatry. 2011;72:1660–1668. doi:10.4088/JCP.10r06531
  • Calvi A, Fischetti I, Verzicco I, et al. Antidepressant drugs effects on blood pressure. Front Cardiovasc Med. 2021;8:704281. doi:10.3389/fcvm.2021.704281
  • Mercurio M, de Filippis R, Spina G, et al. The use of antidepressants is linked to bone loss: a systematic review and metanalysis. Orthop Rev. 2022;14:38564.
  • Miguel C, Albuquerque E. Drug interaction in psycho-oncology: antidepressants and antineoplastics. Pharmacology. 2011;88:333–339. doi:10.1159/000334738
  • Byeon E, Park JC, Hagiwara A, et al. Two antidepressants fluoxetine and sertraline cause growth retardation and oxidative stress in the marine rotifer Brachionus koreanus. Aquat Toxicol Amst Neth. 2020;218:105337. doi:10.1016/j.aquatox.2019.105337
  • Khanzode SD, Dakhale GN, Khanzode SS, et al. Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors. Redox Rep Commun Free Radic Res. 2003;8:365–370.
  • Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl. 2022;12:7–11. doi:10.1016/j.kisu.2021.11.003
  • Bello AK, Okpechi IG, Osman MA, et al. Epidemiology of haemodialysis outcomes. Nat Rev Nephrol. 2022;18:378–395. doi:10.1038/s41581-022-00542-7
  • Canaud B, Tong L, Tentori F, et al. Clinical practices and outcomes in elderly hemodialysis patients: results from the dialysis outcomes and practice patterns study (DOPPS). Clin J Am Soc Nephrol CJASN. 2011;6:1651–1662. doi:10.2215/CJN.03530410
  • Vodošek Hojs N, Bevc S, Ekart R, et al. Oxidative stress markers in chronic kidney disease with emphasis on diabetic nephropathy. Antioxidants. 2020;9:925. doi:10.3390/antiox9100925
  • Irazabal MV, Torres VE. Reactive oxygen species and redox signaling in chronic kidney disease. Cells. 2020;9:1342. doi:10.3390/cells9061342
  • Handelman GJ, Walter MF, Adhikarla R, et al. Elevated plasma F2-isoprostanes in patients on long-term hemodialysis. Kidney Int. 2001;59:1960–1966. doi:10.1046/j.1523-1755.2001.0590051960.x
  • Tarng DC, Huang TP, Wei YH, et al. 8-hydroxy-2’-deoxyguanosine of leukocyte DNA as a marker of oxidative stress in chronic hemodialysis patients. Am J Kidney Dis Off J Natl Kidney Found. 2000;36:934–944. doi:10.1053/ajkd.2000.19086
  • Shimoike T, Inoguchi T, Umeda F, et al. The meaning of serum levels of advanced glycosylation end products in diabetic nephropathy. Metabolism. 2000;49:1030–1035. doi:10.1053/meta.2000.7738
  • Dozio E, Caldiroli L, Molinari P, et al. Accelerated AGEing: the impact of advanced glycation end products on the prognosis of chronic kidney disease. Antioxidants. 2023;12:584. doi:10.3390/antiox12030584
  • Kato H, Watanabe H, Imafuku T, et al. Advanced oxidation protein products contribute to chronic kidney disease-induced muscle atrophy by inducing oxidative stress via CD36/NADPH oxidase pathway. J Cachexia Sarcopenia Muscle. 2021;12:1832–1847. doi:10.1002/jcsm.12786
  • Ravarotto V, Bertoldi G, Innico G, et al. The pivotal role of oxidative stress in the pathophysiology of cardiovascular-renal remodeling in kidney disease. Antioxidants. 2021;10:1041. doi:10.3390/antiox10071041
  • Satou R, Cypress MW, Woods TC, et al. Blockade of sodium-glucose cotransporter 2 suppresses high glucose-induced angiotensinogen augmentation in renal proximal tubular cells. Am J Physiol - Ren Physiol. 2020;318:F67–F75. doi:10.1152/ajprenal.00402.2019
  • Zaibi N, Li P, Xu S-Z. Protective effects of dapagliflozin against oxidative stress-induced cell injury in human proximal tubular cells. PLoS One. 2021;16:e0247234. doi:10.1371/journal.pone.0247234
  • Hasan R, Lasker S, Hasan A, et al. Canagliflozin ameliorates renal oxidative stress and inflammation by stimulating AMPK–Akt–eNOS pathway in the isoprenaline-induced oxidative stress model. Sci Rep. 2020;10:14659. doi:10.1038/s41598-020-71599-2
  • Das NA, Carpenter AJ, Belenchia A, et al. Empagliflozin reduces high glucose-induced oxidative stress and miR-21-dependent TRAF3IP2 induction and RECK suppression, and inhibits human renal proximal tubular epithelial cell migration and epithelial-to-mesenchymal transition. Cell Signal. 2020;68:109506. doi:10.1016/j.cellsig.2019.109506
  • Fang R, Chen J, Long J, et al. Empagliflozin improves kidney senescence induced by d-galactose by reducing sirt1-mediated oxidative stress. Biogerontology. 2023;24:771–782. doi:10.1007/s10522-023-10038-x
  • Semo D, Obergassel J, Dorenkamp M, et al. The sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin reverses hyperglycemia-induced monocyte and endothelial dysfunction primarily through glucose transport-independent but redox-dependent mechanisms. J Clin Med. 2023;12:1356. doi:10.3390/jcm12041356
  • Plantinga Y, Ghiadoni L, Magagna A, et al. Supplementation with vitamins C and E improves arterial stiffness and endothelial function in essential hypertensive patients. Am J Hypertens. 2007;20:392–397. doi:10.1016/j.amjhyper.2006.09.021
  • Tessier DM, Khalil A, Trottier L, et al. Effects of vitamin C supplementation on antioxidants and lipid peroxidation markers in elderly subjects with type 2 diabetes. Arch Gerontol Geriatr. 2009;48:67–72. doi:10.1016/j.archger.2007.10.005
  • Mazloom Z, Hejazi N, Dabbaghmanesh M-H, et al. Effect of vitamin C supplementation on postprandial oxidative stress and lipid profile in type 2 diabetic patients. Pak J Biol Sci PJBS. 2011;14:900–904. doi:10.3923/pjbs.2011.900.904
  • Ulker S, McKeown PP, Bayraktutan U. Vitamins reverse endothelial dysfunction through regulation of eNOS and NAD(P)H oxidase activities. Hypertens Dallas Tex 1979. 2003;41:534–539.
  • Boonthongkaew C, Tong-Un T, Kanpetta Y, et al. Vitamin C supplementation improves blood pressure and oxidative stress after acute exercise in patients with poorly controlled type 2 diabetes mellitus: a randomized,: placebo-controlled, cross-over study. Chin J Physiol. 2021;64:16–23. doi:10.4103/cjp.cjp_95_20
  • Rodrigo R, Prat H, Passalacqua W, et al. Decrease in oxidative stress through supplementation of vitamins C and E is associated with a reduction in blood pressure in patients with essential hypertension. Clin Sci Lond Engl 1979. 2008;114:625–634.
  • Hajjar IM, George V, Sasse EA, et al. A randomized: double-blind, controlled trial of vitamin C in the management of hypertension and lipids. Am J Ther. 2002;9:289–293. doi:10.1097/00045391-200207000-00005
  • Guan Y, Dai P, Wang H. Effects of vitamin C supplementation on essential hypertension: a systematic review and meta-analysis. Medicine (Baltimore. 2020;99:e19274. doi:10.1097/MD.0000000000019274
  • Sato K, Dohi Y, Kojima M, et al. Effects of ascorbic acid on ambulatory blood pressure in elderly patients with refractory hypertension. Arzneimittelforschung. 2006;56:535–540.
  • Mason SA, Della Gatta PA, Snow RJ, et al. Ascorbic acid supplementation improves skeletal muscle oxidative stress and insulin sensitivity in people with type 2 diabetes: findings of a randomized controlled study. Free Radic Biol Med. 2016;93:227–238. doi:10.1016/j.freeradbiomed.2016.01.006
  • El-Aal AA, El-Ghffar EAA, Ghali AA, et al. The effect of vitamin C and/or E supplementations on type 2 diabetic adult males under metformin treatment: a single-blinded randomized controlled clinical trial. Diabetes Metab Syndr. 2018;12:483–489. doi:10.1016/j.dsx.2018.03.013
  • Mason SA, Rasmussen B, van Loon LJC, et al. Ascorbic acid supplementation improves postprandial glycaemic control and blood pressure in individuals with type 2 diabetes: findings of a randomized cross-over trial. Diabetes Obes Metab. 2019;21:674–682. doi:10.1111/dom.13571
  • Ellulu MS, Rahmat A, Patimah I, et al. Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial. Drug Des Devel Ther. 2015;9:3405–3412. doi:10.2147/DDDT.S83144
  • Fraga CG, Croft KD, Kennedy DO, et al. The effects of polyphenols and other bioactives on human health. Food Funct. 2019;10:514–528. doi:10.1039/C8FO01997E
  • Serban M-C, Sahebkar A, Zanchetti A, et al. Effects of quercetin on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2016;5:e002713.
  • Brüll V, Burak C, Stoffel-Wagner B, et al. Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial. Br J Nutr. 2015;114:1263–1277. doi:10.1017/S0007114515002950
  • Egert S, Bosy-Westphal A, Seiberl J, et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. Br J Nutr. 2009;102:1065–1074. doi:10.1017/S0007114509359127
  • Breuss JM, Atanasov AG, Uhrin P. Resveratrol and its effects on the vascular system. Int J Mol Sci. 2019;20:1523. doi:10.3390/ijms20071523
  • Sweeney M, Burns G, Sturgeon N, et al. The effects of berry polyphenols on the gut microbiota and blood pressure: a systematic review of randomized clinical trials in humans. Nutrients. 2022;14:2263. doi:10.3390/nu14112263
  • Vetrani C, Vitale M, Bozzetto L, et al. Association between different dietary polyphenol subclasses and the improvement in cardiometabolic risk factors: evidence from a randomized controlled clinical trial. Acta Diabetol. 2018;55:149–153. doi:10.1007/s00592-017-1075-x
  • Mokgalaboni K, Ntamo Y, Ziqubu K, et al. Curcumin supplementation improves biomarkers of oxidative stress and inflammation in conditions of obesity, type 2 diabetes and NAFLD: updating the status of clinical evidence. Food Funct. 2021;12:12235–12249. doi:10.1039/D1FO02696H
  • Witte AV, Kerti L, Margulies DS, et al. Effects of resveratrol on memory performance: hippocampal functional connectivity, and glucose metabolism in healthy older adults. J Neurosci. 2014;34:7862–7870. doi:10.1523/JNEUROSCI.0385-14.2014
  • Mahjabeen W, Khan DA, Mirza SA. Role of resveratrol supplementation in regulation of glucose hemostasis: inflammation and oxidative stress in patients with diabetes mellitus type 2: A randomized, placebo-controlled trial. Complement Ther Med. 2022;66:102819. doi:10.1016/j.ctim.2022.102819
  • Du C, Smith A, Avalos M, et al. Blueberries improve pain, gait performance, and inflammation in individuals with symptomatic knee osteoarthritis. Nutrients. 2019;11:290. doi:10.3390/nu11020290
  • Hussain SA, Marouf BH, Ali ZS, et al. Efficacy and safety of co-administration of resveratrol with meloxicam in patients with knee osteoarthritis: a pilot interventional study. Clin Interv Aging. 2018;13:1621–1630. doi:10.2147/CIA.S172758
  • Ávila-Gálvez MÁ, González-Sarrías A, Martínez-Díaz F, et al. Disposition of dietary polyphenols in breast cancer patients’ tumors, and their associated anticancer activity: the particular case of curcumin. Mol Nutr Food Res. 2021;65:2100163. doi:10.1002/mnfr.202100163
  • Huhn S, Beyer F, Zhang R, et al. Effects of resveratrol on memory performance, hippocampus connectivity and microstructure in older adults - a randomized controlled trial. NeuroImage. 2018;174:177–190. doi:10.1016/j.neuroimage.2018.03.023
  • Moussa C, Hebron M, Huang X, et al. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. J Neuroinflammation. 2017;14:1. doi:10.1186/s12974-016-0779-0
  • Baum L, Lam CWK, Cheung SK-K, et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol. 2008;28:110–113. doi:10.1097/jcp.0b013e318160862c
  • Kumar P, Liu C, Suliburk J, et al. Supplementing glycine and N-acetylcysteine (GlyNAC) in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, physical function, and aging hallmarks: a randomized clinical trial. J Gerontol A Biol Sci Med Sci. 2023;78:75–89. doi:10.1093/gerona/glac135
  • Hashemi G, Mirjalili M, Basiri Z, et al. A pilot study to evaluate the effects of oral N-acetyl cysteine on inflammatory and oxidative stress biomarkers in rheumatoid arthritis. Curr Rheumatol Rev. 2019;15:246–253. doi:10.2174/1573403X14666180926100811
  • Esalatmanesh K, Jamali A, Esalatmanesh R, et al. Effects of N-acetylcysteine supplementation on disease activity: oxidative stress, and inflammatory and metabolic parameters in rheumatoid arthritis patients: a randomized double-blind placebo-controlled trial. Amino Acids. 2022;54:433–440. doi:10.1007/s00726-022-03134-8
  • Batooei M, Tahamoli-Roudsari A, Basiri Z, et al. Evaluating the effect of oral N-acetylcysteine as an adjuvant treatment on clinical outcomes of patients with rheumatoid arthritis: a randomized, double blind clinical trial. Rev Recent Clin Trials. 2018;13:132–138. doi:10.2174/1574887113666180307151937
  • Adair JC, Knoefel JE, Morgan N. Controlled trial of N-acetylcysteine for patients with probable Alzheimer’s disease. Neurology. 2001;57:1515–1517. doi:10.1212/WNL.57.8.1515
  • Remington R, Chan A, Paskavitz J, et al. Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer’s disease: a placebo-controlled pilot study. Am J Alzheimers Dis Dementias. 2009;24:27–33. doi:10.1177/1533317508325094
  • Chan A, Paskavitz J, Remington R, et al. Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer’s disease: a 1-year, open-label pilot study with an 16-month caregiver extension. Am J Alzheimers Dis Dementias. 2009;23:571–585. doi:10.1177/1533317508325093
  • Remington R, Bechtel C, Larsen D, et al. A phase II randomized clinical trial of a nutritional formulation for cognition and mood in Alzheimer’s disease. J Alzheimers Dis JAD. 2015;45:395–405. doi:10.3233/JAD-142499
  • Skvarc DR, Dean OM, Byrne LK, et al. The effect of N-acetylcysteine (NAC) on human cognition – a systematic review. Neurosci Biobehav Rev. 2017;78:44–56. doi:10.1016/j.neubiorev.2017.04.013
  • Fasipe B, Faria A, Laher I. Potential for novel therapeutic uses of alpha lipoic acid. Curr Med Chem. 2023;30:3942–3954. doi:10.2174/0929867329666221006115329
  • Rezaei Zonooz S, Hasani M, Morvaridzadeh M, et al. Effect of alpha-lipoic acid on oxidative stress parameters: a systematic review and meta-analysis. J Funct Foods. 2021;87:104774. doi:10.1016/j.jff.2021.104774
  • Jeffrey S, Isaac Samraj P, Sundara Raj B. Therapeutic benefits of alpha-lipoic acid supplementation in diabetes mellitus: a narrative review. J Diet Suppl. 2022;19:566–586. doi:10.1080/19390211.2021.2020387
  • Derosa G, D’Angelo A, Romano D, et al. A clinical trial about a food supplement containing α-lipoic acid on oxidative stress markers in type 2 diabetic patients. Int J Mol Sci. 2016;17:1802. doi:10.3390/ijms17111802
  • Mendoza-Núñez VM, García-Martínez BI, Rosado-Pérez J, et al. The effect of 600 mg alpha-lipoic acid supplementation on oxidative stress, inflammation, and RAGE in older adults with type 2 diabetes mellitus. Oxid Med Cell Longev. 2019;2019:3276958.
  • Gianturco V, Bellomo A, D’ottavio E, et al. Impact of therapy with α-lipoic acid (ALA) on the oxidative stress in the controlled niddm: a possible preventive way against the organ dysfunction? Arch Gerontol Geriatr. 2009;49:129–133. doi:10.1016/j.archger.2009.09.022
  • Zhao L, Hu F-X. α-Lipoic acid treatment of aged type 2 diabetes mellitus complicated with acute cerebral infarction. Eur Rev Med Pharmacol Sci. 2014;18:3715–3719.
  • Porasuphatana S, Suddee S, Nartnampong A, et al. Glycemic and oxidative status of patients with type 2 diabetes mellitus following oral administration of alpha-lipoic acid: a randomized double-blinded placebo-controlled study. Asia Pac J Clin Nutr. 2012;21:12–21.
  • Khabbazi T, Mahdavi R, Safa J, et al. Effects of alpha-lipoic acid supplementation on inflammation: oxidative stress, and serum lipid profile levels in patients with end-stage renal disease on hemodialysis. J Ren Nutr. 2012;22:244–250. doi:10.1053/j.jrn.2011.06.005
  • Ramos LF, Kane J, McMonagle E, et al. Effects of combination tocopherols and alpha lipoic acid therapy on oxidative stress and inflammatory biomarkers in chronic kidney disease. J Ren Nutr Off J Counc Ren Nutr Natl Kidney Found. 2011;21:211–218.
  • Himmelfarb J, Ikizler TA, Ellis C, et al. Provision of antioxidant therapy in hemodialysis (PATH): a randomized clinical trial. J Am Soc Nephrol JASN. 2014;25:623–633. doi:10.1681/ASN.2013050545
  • Mahdavi R, Khabbazi T, Safa J. Alpha lipoic acid supplementation improved antioxidant enzyme activities in hemodialysis patients. Int J Vitam Nutr Res Int Z Vitam- Ernahrungsforschung J Int Vitaminol Nutr. 2019;89:161–167. doi:10.1024/0300-9831/a000552
  • Abdel Hamid DZ, Nienaa YA, Mostafa TM. Alpha-lipoic acid improved anemia: erythropoietin resistance, maintained glycemic control, and reduced cardiovascular risk in diabetic patients on hemodialysis: a multi-center prospective randomized controlled study. Eur Rev Med Pharmacol Sci. 2022;26:2313–2329.
  • Díaz-Casado ME, Quiles JL, Barriocanal-Casado E, et al. The paradox of coenzyme Q10 in aging. Nutrients. 2019;11:2221. doi:10.3390/nu11092221
  • Hargreaves I, Heaton RA, Mantle D. Disorders of human coenzyme Q10 metabolism: an overview. Int J Mol Sci. 2020;21:6695. doi:10.3390/ijms21186695
  • Hargreaves IP, Mantle D. Coenzyme Q10 supplementation in fibrosis and aging. Adv Exp Med Biol. 2019;1178:103–112. doi:10.1007/978-3-030-25650-0_6
  • Lee B-J, Huang Y-C, Chen S-J, et al. Coenzyme Q10 supplementation reduces oxidative stress and increases antioxidant enzyme activity in patients with coronary artery disease. Nutrition. 2012;28:250–255. doi:10.1016/j.nut.2011.06.004
  • Yeung CK, Billings FT, Claessens AJ, et al. Coenzyme Q10 dose-escalation study in hemodialysis patients: safety, tolerability, and effect on oxidative stress. BMC Nephrol. 2015;16:183. doi:10.1186/s12882-015-0178-2
  • Rivara MB, Yeung CK, Robinson-Cohen C, et al. Effect of coenzyme Q10 on biomarkers of oxidative stress and cardiac function in hemodialysis patients: the CoQ10 biomarker trial. Am J Kidney Dis Off J Natl Kidney Found. 2017;69:389–399. doi:10.1053/j.ajkd.2016.08.041
  • The Heart Outcomes Prevention Evaluation Study Investigators. Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med. 2000;342:154–160. doi:10.1056/NEJM200001203420302
  • Lee I-M, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. JAMA. 2005;294:56–65. doi:10.1001/jama.294.1.56
  • Nascimento MM, Suliman ME, Silva M, et al. Effect of oral N-acetylcysteine treatment on plasma inflammatory and oxidative stress markers in peritoneal dialysis patients: a placebo-controlled study. Perit Dial Int J Int Soc Perit Dial. 2010;30:336–342. doi:10.3747/pdi.2009.00073
  • Renke M, Tylicki L, Rutkowski P, et al. The effect of N-acetylcysteine on blood pressure and markers of cardiovascular risk in non-diabetic patients with chronic kidney disease: a placebo-controlled, randomized, cross-over study. Med Sci Monit Int Med J Exp Clin Res. 2010;16:PI13–PI18.
  • Zhang Y, Han P, Wu N, et al. Amelioration of lipid abnormalities by α-lipoic acid through antioxidative and anti-inflammatory effects. Obesity. 2011;19:1647–1653. doi:10.1038/oby.2011.121
  • Bobe G, Michels AJ, Zhang W-J, et al. A randomized controlled trial of long-term (R)-α-lipoic acid supplementation promotes weight loss in overweight or obese adults without altering baseline elevated plasma triglyceride concentrations. J Nutr. 2020;150:2336–2345. doi:10.1093/jn/nxaa203
  • Ahmadi A, Mazooji N, Roozbeh J, et al. Effect of alpha-lipoic acid and vitamin E supplementation on oxidative stress,: inflammation, and malnutrition in hemodialysis patients. Iran J Kidney Dis. 2013;7:461–467.
  • Pérez-Torres I, Guarner-Lans V, Rubio-Ruiz ME. Reductive stress in inflammation-associated diseases and the pro-oxidant effect of antioxidant agents. Int J Mol Sci. 2017;18:2098. doi:10.3390/ijms18102098