Metformin Alleviates Altered Erythrocyte Redox Status During Aging in Rats

Rejuvenation Res. 2017 Feb;20(1):15-24. doi: 10.1089/rej.2016.1826. Epub 2016 Jun 23.

Abstract

Metformin, a biguanide drug commonly used to treat type 2 diabetes, has been noted to function as a caloric restriction mimetic. Its antidiabetic effect notwithstanding, metformin is currently being considered an antiaging drug candidate, although the molecular mechanisms have not yet been unequivocally established. This study aims to examine whether short-term metformin treatment can provide protective effects against oxidative stress in young and old-age rats. Young (age 4 months) and old (age 24 months) male Wistar rats were treated with metformin (300 mg/kg b.w.) for 4 weeks. At the end of the treatment period, an array of biomarkers of oxidative stress were evaluated, including plasma antioxidant capacity measured in terms of ferric reducing ability of plasma (FRAP), reactive oxygen species (ROS), lipid peroxidation (MDA), reduced glutathione (GSH), total plasma thiol (SH), plasma membrane redox system (PMRS), protein carbonyl (PCO), advanced oxidation protein products (AOPPs), and advanced glycation end products (AGEs) in control and experimental groups. Metformin treatment resulted in an increase in FRAP, GSH, SH, and PMRS activities in both age groups compared to respective controls. On the other hand, treated groups exhibited significant reductions in ROS, MDA, PCO, AOPP, and AGE level. Save for FRAP and protein carbonyl, the effect of metformin on all other parameters was more pronounced in old-aged rats. Metformin caused a significant increase in the PMRS activity in young rats, however, the effect was less pronounced in old rats. These findings provide evidence with respect to restoration of antioxidant status in aged rats after short-term metformin treatment. The findings substantiate the putative antiaging role of metformin.

Keywords: aging; erythrocyte; metformin; oxidative stress; rat.

MeSH terms

  • Aging / metabolism*
  • Animals
  • Antioxidants / metabolism
  • Cholesterol / blood
  • Erythrocyte Membrane / metabolism
  • Erythrocytes / drug effects
  • Erythrocytes / metabolism*
  • Glutathione / metabolism
  • Glycation End Products, Advanced / metabolism
  • Lipid Peroxidation / drug effects
  • Lipoproteins, LDL / blood
  • Male
  • Metformin / pharmacology*
  • Oxidation-Reduction / drug effects
  • Protective Agents / pharmacology
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Sulfhydryl Compounds / metabolism

Substances

  • Antioxidants
  • Glycation End Products, Advanced
  • Lipoproteins, LDL
  • Protective Agents
  • Reactive Oxygen Species
  • Sulfhydryl Compounds
  • Metformin
  • Cholesterol
  • Glutathione