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 language | English |
|---|---|
| Pages (from-to) | 75-83 |
| Number of pages | 9 |
| Journal | European Journal of Pharmacology |
| Volume | 424 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 13 2001 |
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Keywords
- Gentamicin
- Nitric oxide (NO)
- Peroxynitrite
- Poly(ADP ribose)synthetase
- Renal injury
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Pharmacology
Cite this
Effect of N-acetylcysteine on gentamicin-mediated nephropathy in rats. / Mazzon, Emanuela; Britti, Domenico; De Sarro, Angela; Caputi, Achille P.; Cuzzocrea, Salvatore.
In: European Journal of Pharmacology, Vol. 424, No. 1, 13.07.2001, p. 75-83.Research output: Contribution to journal › Article
}
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 -