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 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.
Mazzon
E
E
Department of Biomorphology, School of Medicine, University of Messina, Messina, Italy.
Britti
D
D
De Sarro
A
A
Caputi
A P
AP
Cuzzocrea
S
S
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005839:Gentamicins / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000378:metabolism
D016166:Free Radical Scavengers; D005839:Gentamicins; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D009195:Peroxidase; D011065:Poly(ADP-ribose) Polymerases; D000111:Acetylcysteine