Attenuation of gentamicin-induced nephrotoxicity: trimetazidine versus N-acetyl cysteine.
Gentamicin (G) is a highly nephrotoxic aminoglucoside. It was used to experimentally induce nephrotoxicity in male Wistar rats. To find a drug capable of protecting the nephron we assayed a cardioprotector (trimetazidine, TMZ) and a hepatoprotector (N-acetyl cysteine, NAC). The rats were divided into six groups (n = 8): (A) control without drugs; (B) treated with 50 mg kg(-1) per day (i.p.) of G for 7 days; (C) diet supplemented with 20 mg kg(-1) per day of TMZ for 7 days; (D) treated with 10 mg kg(-1) per day (i.p.) of NAC for 7 days; (E) pretreated for 7 days with 20 mg kg(-1) per day of TMZ and during the following 7 days with G + TMZ; (F) pretreated for 7 days with 10 mg kg(-1) per day (i.p.) of NAC and during the following 7 days with G + NAC. Urea and creatinine as well as the excretion of urinary gamma-glutamyl transpeptidase (GGT(u)) and urinary N-acetyl-glucosaminidase (NAG(u)) were determined and structural and ultrastructural studies were carried out. Group B was used as a G-induced nephrotoxicity control. Pretreatment with TMZ (E) showed a protector effect against induced nephrotoxicity, with no biochemical or functional changes nor alterations in histoarchitecture or ultrastructure. Pretreatment with NAC (F) showed no protector effect against G-induced nephrotoxicity since no statistically significant differences were found with respect to the control group with G. We conclude that G-induced nephrotoxicity is attenuated by the cytoprotective effect of TMZ. We may infer that TMZ inhibits the reabsorption and consequently the accumulation of G in the proximal tubule cell.
De la Cruz Rodríguez
Lilia Cristina
LC
Instituto de Bioquímica Aplicada, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Balcarce 747, 4000 San Miguel de Tucumán, Tucumán, Argentina. vicedecanato@fbqf.unt.edu.ar
Araujo
Carmen Rosa
CR
Posleman
Sara Emilia
SE
Rey
María Rosario
MR
D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000097:blood; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use*; D005839:Gentamicins / Q000009:adverse effects*; D007672:Kidney Cortex / Q000187:drug effects / Q000648:ultrastructure; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009399:Nephrons / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D014292:Trimetazidine / Q000008:administration & dosage / Q000627:therapeutic use*; D005723:gamma-Glutamyltransferase / Q000652:urine
D015415:Biomarkers; D016166:Free Radical Scavengers; D005839:Gentamicins; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D000118:Acetylglucosaminidase; D014292:Trimetazidine; D000111:Acetylcysteine