Use of a bioengineered antioxidant in mouse models of metabolic syndrome

ABSTRACT

Background: Oxidative stress has been implicated in metabolic syndrome (MetS); however, antioxidants such as vitamin E have had limited success in the clinic. This prompts the question of what effects amore potent antioxidant might produce. A prime candidate is the recently developed bioengineered antioxidant, poly(ethylene glycol)-functionalizedhydrophilic carbon clusters (PEG-HCCs), which are capable of neutralizing the reactive oxygen species (ROS) superoxide anion and hydroxyl radical at10⁶/molecule of PEG-HCC. In this project, we tested the potential of PEG-HCCs as a possible therapeutic for MetS.

Results: PEG-HCC treatment lessened lipid peroxidation, aspartate aminotransferase levels, non-fastingblood glucose levels, and JNK phosphorylation inob/ob mice. PEG-HCC-treated WT mice had an increased response to insulin by insulin tolerance tests and adecrease in blood glucose by glucose tolerance tests. These effects were not observed in HFD-fed mice, regardless of treatment. PEG-HCCs were observed in the interstitial space of liver, spleen, skeletal muscle, and adipose tissue. No significant difference was shown in gluconeogenesis or inflammatory gene expression between treatment and dietary groups.

Expert Opinion: PEG-HCCs improved some parameters of disease possibly due to a resulting increase in peripheral insulin sensitivity. However, additional studies are needed to elucidate how PEG-HCCsare producing these effects.

KEYWORDS:

• Obesity
• metabolic syndrome
• hyperglycemia
• reactive oxygen species
• oxidative stress
• antioxidant
• insulin resistance
• prediabetes

Author Contributions

DMG, BRB, and ZCII were involved in the study design, data collection, data analysis, and interpretation and writing of the manuscript. DM and JMB were involved in the synthesis and validation of the PEG-HCCs, study design, data interpretation, as well as the writing of the manuscript. TAK, JMT, SLS, and RGP were all involved in the study design, data interpretation as well as in the writing of the manuscript.

Declaration of interest

TA Kent and JM Tour are members of and own shares in Acelerox, LLC to commercialize the medical use of carbon nanoantioxidants. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

D Griffin was funded by an HHMI Gilliam fellowship. The work at Rice University was funded by the Department of Defense through the Mission Connect Mild Traumatic Brain Injury Consortium (W81XWH-08-2-0143) and the Alliance for NanoHealth (W81XWH-09-02-0139). The work at BCM was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (R21DK093802) and the National Institute of Neurological Disorders and Stroke (R21NS084290 and R01NS094535) and Welch Foundation Grant BE-0048 (T.A.K.).