TY - JOUR
T1 - Effect of N-acetylcysteine on gentamicin-mediated nephropathy in rats
AU - Mazzon, Emanuela
AU - Britti, Domenico
AU - De Sarro, Angela
AU - Caputi, Achille P.
AU - Cuzzocrea, Salvatore
PY - 2001/7/13
Y1 - 2001/7/13
N2 - 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.
AB - 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.
KW - Gentamicin
KW - Nitric oxide (NO)
KW - Peroxynitrite
KW - Poly(ADP ribose)synthetase
KW - Renal injury
UR - http://www.scopus.com/inward/record.url?scp=0035854556&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035854556&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(01)01130-X
DO - 10.1016/S0014-2999(01)01130-X
M3 - Article
C2 - 11470263
AN - SCOPUS:0035854556
VL - 424
SP - 75
EP - 83
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1
ER -