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

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 fail ure, characterised by a significantly decreased creatinine clearance and in creased blood creatinine levels, fractional excretion of sodium Na+, lithiu m Li+, urine gamma glutamyl transferase and daily urine volume. A significa nt increase in kidney myeloperoxidase activity and lipid peroxidation was o bserved in gentamicin-treated rats. Immunohistochemical localisation demons trated nitrotyrosine formation and poly(ADP-ribose)synthase activation in t he proximal tubule from gentamicin-treated rats. Renal histology examinatio n confirmed the tubular necrosis. N-acetylcysteine (10 mg/kg i.p. for 5 day s) caused normalisation of the above biochemical parameters. In addition, N -acetylcysteine treatment significantly prevents the gentamicin-induced tub ular necrosis. These results suggest that (1) N-acetylcysteine has protecti ve effects on gentamicin-mediated nephropathy, and (2) the mechanisms of th e protective effects can be, at least in part, related to interference with peroxynitrite-related pathways. (C) 2001 Published by Elsevier Science B.V .