Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway

Kidney Int. 2010 May;77(10):861-9. doi: 10.1038/ki.2010.11. Epub 2010 Feb 17.


The antidiabetic drug metformin can diminish apoptosis induced by oxidative stress in endothelial cells and prevent vascular dysfunction even in nondiabetic patients. Here we tested whether it has a beneficial effect in a rat model of gentamicin toxicity. Mitochondrial analysis, respiration intensity, levels of reactive oxygen species, permeability transition, and cytochrome c release were assessed 3 and 6 days after gentamicin administration. Metformin treatment fully blocked gentamicin-mediated acute renal failure. This was accompanied by a lower activity of N-acetyl-beta-D-glucosaminidase, together with a decrease of lipid peroxidation and increase of antioxidant systems. Metformin also protected the kidney from histological damage 6 days after gentamicin administration. These in vivo markers of kidney dysfunction and their correction by metformin were complemented by in vitro studies of mitochondrial function. We found that gentamicin treatment depleted respiratory components (cytochrome c, NADH), probably due to the opening of mitochondrial transition pores. These injuries, partly mediated by a rise in reactive oxygen species from the electron transfer chain, were significantly decreased by metformin. Thus, our study suggests that pleiotropic effects of metformin can lessen gentamicin nephrotoxicity and improve mitochondrial homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosaminidase / metabolism
  • Acetylglucosaminidase / pharmacology
  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Cytochrome c Group
  • Cytochromes c / metabolism
  • Cytochromes c / pharmacology
  • Electron Transport / drug effects
  • Gentamicins / metabolism
  • Gentamicins / pharmacology*
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / pharmacology*
  • Kidney / metabolism
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Lipid Peroxidation / drug effects
  • Male
  • Metformin / metabolism
  • Metformin / pharmacology*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism*
  • Mitochondria / physiology
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Permeability
  • Rats
  • Reactive Oxygen Species / metabolism
  • Reactive Oxygen Species / pharmacology


  • Antioxidants
  • Cytochrome c Group
  • Gentamicins
  • Hypoglycemic Agents
  • Reactive Oxygen Species
  • cytochrome c''
  • Cytochromes c
  • Metformin
  • Acetylglucosaminidase