Renal and hepatic function in rats treated with cyclosporin A in combination with gentamicin or cephalosporin antibiotics.
Sprague-Dawley rats received cyclosporin A (25 mg/kg) together with either the aminoglycoside gentamicin (50 mg/kg) or one of 3 cephalosporin antibiotics (100 mg/kg) daily for 14 days. Only minor impairment of renal or hepatic function was observed when either cyclosporin A or gentamicin was given on its own and no abnormality was seen in response to cephalosporins. However, concomitant administration of cyclosporin A and gentamicin caused acute renal failure, accompanied by cyclosporin A-induced damage to the proximal straight tubule and gentamicin-induced proximal convoluted tubular cell necrosis. In contrast, the structural abnormalities present in the 3 groups given cephalosporins in addition to cyclosporin A were attributable only to the immune suppressant. Liver functional changes previously found only at higher doses of cyclosporin A were observed in the cyclosporin A/gentamicin group and there was some evidence of possible interactions between cyclosporin A and each cephalosporin affecting liver function. The results indicate that treatment of infection with cephalosporin antibiotics or a less nephrotoxic aminoglycoside is preferable to gentamicin in cyclosporin A-treated patients.
D000118:Acetylglucosaminidase / Q000378:metabolism; D058186:Acute Kidney Injury / Q000139:chemically induced; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002511:Cephalosporins / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D003524:Cyclosporins / Q000633:toxicity*; D004357:Drug Synergism; D005839:Gentamicins / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced*; D007684:Kidney Tubules / Q000473:pathology; D008099:Liver / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014508:Urea / Q000097:blood
D001798:Blood Proteins; D002511:Cephalosporins; D003524:Cyclosporins; D005839:Gentamicins; D014508:Urea; D000118:Acetylglucosaminidase