Streptozotocin-induced diabetic cardiomyopathy in rats: ameliorative effect of PIPERINE via Bcl2, Bax/Bcl2, and caspase-3 pathways

ABSTRACT

The objective of present investigation was to appraise the effects of piperine on STZ-induced diabetic cardiomyopathy in rats. Diabetes was induced in Sprague-Dawley rats with intraperitoneal STZ injection, and the rats were assigned to seven groups. Electrocardiograph, hemodynamic, various biochemical, molecular, and histological parameters were examined. Treatment with piperine significantly (p < 0.05) restored altered myocardial functions, inhibited cardiac marker, and restored electrocardiogram and hemodynamic alterations. The elevated level of cardiac oxido-nitrosative stress and decreased cardiac Na-K-ATPase concentration, after STZ administration, were significantly (p < 0.05) attenuated by piperine treatment. Piperine also considerably (p < 0.05) increased myocardial mitochondrial enzyme activity. STZ-induced alteration in heart ANP, BNP, cTn-I, Bcl2, Bax/Bcl2, and caspase3 mRNA expression was significantly (p < 0.05) restored by piperine treatment. Piperine administration reduced histopathological aberrations induced by STZ. In conclusion, the present investigation suggests that piperine ameliorates STZ-induced diabetic cardiomyopathy via modulation of caspase-3, Bcl2, Bax/Bcl2 pathways.

Abbreviations: ACE: Angiotensin-Converting Enzyme; ANOVA: Analysis of Variance; ANP: Atrial Natriuretic Peptide; APAF: Apoptotic Protease-Activating Factor; ARB: Angiotensin Receptor Blockers; ATP: Adenosine Triphosphate; Bax: Bcl-2-associated X protein; Bcl2: B-cell lymphoma 2; BPM: Beats Per Minute; BNP: brain natriuretic peptide; CAD: Caspase-3-Activated DNase; cDNA: Complementary DNA; CK-MB: Creatine Kinase-MB; CPCSEA: Committee for the Purpose of Control And Supervision of Experiments on Animals; cTn-I: cardiac troponin I; DBP: Diastolic Blood Pressure; DCM: Diabetic Cardiomyopathy; DNA: Deoxyribonucleic Acid; DPX: DisterenePhthalate Xylene; ECG: Electrocardiogram; ETC: Electron Transport Chain; GOD-POD: Glucose Oxidase Peroxidase; GSH: Glutathione; IAEC: Institutional Animal Ethics Committee; IL-6: Interleukin-6; IL-1b: Interleukin-1b; LDH: Lactate Dehydrogenase; LV: Left Ventricle; LVEDP: left ventricular end-diastolic Pressure; MABP: Mean Arterial Blood Pressure; MDA: Malondialdehyde; mRNA: Messenger Ribonucleic Acid; MTT: 3- (4,5-Dimethylthiazol-2-yl)-2,5-DiphenyltetrazoliumBromide; NADH: Nicotinamide Adenine Dinucleotide Phosphate; NADPH: Nicotinamide Adenine Dinucleotide Phosphate Hydrogen; NO: nitric oxide; NP: Natriuretic Peptides; OXPHOS: Oxidative Phosphorylation; p.o.: per os; PCR: Polymerase Chain Reaction; RT-PCR: Reverse Transcriptionpolymerase Chain Reaction; PPAR: Peroxisome Proliferator-Activated Receptor Gamma; RAS: Renin-Angiotensin System; RNA: Ribonucleic Acid; ROS: Reactive Oxygen Species; SBP: Systolic Blood Pressure; SDH: Succinate Dehydrogenase; SEM: Standard Error Means; SOD: superoxide dismutase: STZ: Streptozotocin; TNF: Tumor Necrosis Factor Alpha; TnI: Troponin I

Graphical Abstract

Piperine Ameliorates Streptozotocin-Induced Diabetic Cardiomyopathy in Rats.

KEYWORDS:

• Bax
• Bcl2
• cTn-I
• diabetic cardiomyopathy
• piperine

Author’s contribution

YW: Concepts, Design, Manuscript preparation, Manuscript editing, Manuscript review

HS: Experimental studies, Data acquisition, Manuscript editing, Manuscript review

JZ: Concepts, Design, Statistical analysis, Manuscript review

ZX: Concepts, Manuscript preparation, Manuscript editing, Manuscript review

CX: Data acquisition, Manuscript editing, Manuscript review

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This project was funded by Nanchong municipal government and North Sichuan Medical College scientific research strategic cooperation project (18SXHZ0295).