Influence of iron, deferoxamine and ascorbic acid on gentamicin-induced nephrotoxicity in rats.
1. Nephrotoxicity was induced in rats by injecting gentamicin intramuscularly (i.m.) at a dose of 80 mg/kg for 6 days. Treated animals demonstrated a typical pattern of nephrotoxicity characterized by increased serum creatinine and urea concentrations, and by necrosis of proximal tubular epithelium. 2. Pretreatment of rats with iron (Fe3+) at daily i.m. doses of 2, 4 and 8 mg/kg for 14 days, with gentamicin given during the last 6 days of treatment, significantly potentiated the gentamicin-induced increases in creatinine and urea concentrations and exacerbated renal histological damage. 3. Gentamicin significantly increased serum Fe3+ concentration in rats treated with Fe3+ and gentamicin, compared to Fe(3+)-treated rats. 4. The Fe3+ antidote deferoxamine (100 mg/kg, i.m.) given with gentamicin was ineffective in antagonizing the potentiating effect of Fe3+ on gentamicin-induced nephrotoxicity. 5. Ascorbic acid (50 mg/kg, i.m. for 14 days) was ineffective in altering the nephrotoxicity of gentamicin (80 mg/kg) given during the last 6 days of treatment. At a dose of 100 mg/kg for 14 days, ascorbic acid significantly reduced gentamicin-induced increases in creatinine and urea levels, and ameliorated proximal tubular damage. However, at a dose of 200 mg/kg, ascorbic acid exacerbated gentamicin-induced increases in creatinine and urea levels and increased the severity of the histological damage.
Ben Ismail
T H
TH
Department of Pharmacology, Faculty of Medicine, Al-Arab Medical University, Benghazi, Libya.
Ali
B H
BH
Bashir
A A
AA
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D003676:Deferoxamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005839:Gentamicins / Q000633:toxicity*; D007501:Iron / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley
D005839:Gentamicins; D003404:Creatinine; D007501:Iron; D003676:Deferoxamine; D001205:Ascorbic Acid