Effect of N-acetylcysteine on gentamicin-mediated nephropathy in rats

Emanuela Mazzon, Domenico Britti, Angela De Sarro, Achille P. Caputi, Salvatore Cuzzocrea

Research output: Contribution to journalArticlepeer-review

Abstract

Studies were performed on the mechanisms of the protective effects of free-radical scavengers against gentamicin-mediated nephropathy. Administration of gentamicin, 100 mg/kg s.c., for 5 days to rats induced marked renal failure, characterised by a significantly decreased creatinine clearance and increased blood creatinine levels, fractional excretion of sodium Na+, lithium Li+, urine gamma glutamyl transferase and daily urine volume. A significant increase in kidney myeloperoxidase activity and lipid peroxidation was observed in gentamicin-treated rats. Immunohistochemical localisation demonstrated nitrotyrosine formation and poly(ADP-ribose)synthase activation in the proximal tubule from gentamicin-treated rats. Renal histology examination confirmed the tubular necrosis. N-acetylcysteine (10 mg/kg i.p. for 5 days) caused normalisation of the above biochemical parameters. In addition, N-acetylcysteine treatment significantly prevents the gentamicin-induced tubular necrosis. These results suggest that (1) N-acetylcysteine has protective effects on gentamicin-mediated nephropathy, and (2) the mechanisms of the protective effects can be, at least in part, related to interference with peroxynitrite-related pathways.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalEuropean Journal of Pharmacology
Volume424
Issue number1
DOIs
Publication statusPublished - Jul 13 2001

Keywords

  • Gentamicin
  • Nitric oxide (NO)
  • Peroxynitrite
  • Poly(ADP ribose)synthetase
  • Renal injury

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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