Comparative modulating effects of captopril, diltiazem, dietary calcium and pyridoxal-5'-phosphate on gentamicin-induced nephrotoxicity in the rat.
1. Nephrotoxicity was induced in rats by injecting gentamicin intramuscularly (i.m.) at a dose of 80 mg/kg/day for 6 days. Treated animals demonstrated a typical pattern of aminoglycoside nephrotoxicity characterized histopathologically by necrosis of proximal tubular epithelium, and biochemically by increased serum creatinine and urea concentrations. Reduced glutathione (GSH) concentration in renal cortex was significantly decreased by gentamicin. 2. Simultaneous treatment of rats with gentamicin and either captopril or diltiazem significantly potentiated the gentamicin-induced increases in serum creatinine and urea and did not significantly affect the gentamicin-induced decrease in cortical GSH concentration. 3. Concomitant treatment with gentamicin and either Ca2+ or pyridoxal-5'-phosphate decreased serum urea level, did not significantly affect serum creatinine concentration, and significantly increased cortical GSH concentration in comparison to the values of these parameters following gentamicin treatment. 4. Histopathologically, the severity of gentamicin-induced renal damage was exacerbated by captopril, and even more so by diltiazem. Simultaneous treatment with gentamicin and either Ca2+ or pyridoxal-5'-phosphate produced only mild focal atrophy of renal tubular epithelium. Control rats had apparently normal histology. 5. In conclusion, captopril and diltiazem, at the doses used, significantly potentiated gentamicin-induced nephrotoxicity to a broadly similar extent. Although Ca2+ and pyridoxal-5'-phosphate, at the doses used, reduced significantly the severity of some of the manifestations of nephrotoxicity, they were equally ineffective in completely preventing the development of nephrotoxicity.
Ali
B H
BH
Department of Pharmacology, Faculty of Medicine, Al-Arab Medical University, Benghazi, Libya.
Bashir
A A
AA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002136:Calcium, Dietary / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D007273:Injections, Intramuscular; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007677:Kidney Function Tests; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002136:Calcium, Dietary; D005839:Gentamicins; D011732:Pyridoxal Phosphate; D002216:Captopril; D004110:Diltiazem; D005978:Glutathione