Inhibition of mitochondrial respiratory chain in the brain of rats after renal ischemia is prevented by N-acetylcysteine and deferoxamine

Metab Brain Dis. 2010 Jun;25(2):219-25. doi: 10.1007/s11011-010-9187-9. Epub 2010 Apr 28.

Abstract

We evaluated the activities of mitochondrial respiratory chain complexes in the brain of rats after renal ischemia and the effect of administration of the antioxidants N-acetylcysteine (NAC) and deferoxamine (DFX). The rats were divided into the groups: sham (control) or renal ischemia treated with saline, NAC 20 mg/kg, DFX 20 mg/kg or both antioxidants. Complex I activity was inhibited in hippocampus, striatum, prefrontal cortex and cerebral cortex of rats 1 and 6 h after renal ischemia and that the treatment with a combination of NAC and DFX prevented such effect. Complex I activity was not altered in hippocampus, striatum, prefrontal cortex and cerebral cortex of rats 12 h after renal ischemia. Complexes II and III activities were not altered in hippocampus, striatum, prefrontal cortex and cerebral cortex of rats 1, 6 and 12 h after renal ischemia. Complex IV activity was inhibited in hippocampus, striatum, prefrontal cortex and cerebral cortex of rats 1 h after renal ischemia, but the treatment with the combination of NAC and DFX was able to prevent this inhibition. Complex IV activity was not altered in hippocampus, striatum, prefrontal cortex and cerebral cortex of rats 6 and 12 h after renal ischemia. These results suggest that the inhibition of mitochondrial respiratory chain after renal ischemia might play a role in the pathogenesis of uremic encephalopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Animals
  • Cell Respiration / drug effects
  • Cell Respiration / physiology
  • Deferoxamine / pharmacology*
  • Disease Models, Animal
  • Drug Combinations
  • Drug Synergism
  • Electron Transport / drug effects*
  • Electron Transport / physiology
  • Electron Transport Complex I / drug effects*
  • Electron Transport Complex I / metabolism
  • Free Radical Scavengers / pharmacology
  • Ischemia / etiology
  • Ischemia / metabolism*
  • Ischemia / prevention & control*
  • Kidney Diseases / complications
  • Kidney Diseases / metabolism*
  • Kidney Diseases / prevention & control*
  • Male
  • Rats
  • Rats, Wistar

Substances

  • Drug Combinations
  • Free Radical Scavengers
  • Electron Transport Complex I
  • Deferoxamine
  • Acetylcysteine