The combined effect of cyclosporine A and gentamicin on enzymuria in the Sprague-Dawley rat

Male Sprague-Dawley rats (8 per group) were administered a single oral dose of cyclosporine A (10, 30 and 50 mg/day) for 5 days or vehicle (corn oil, 1.5 mL/kg) and urinary enzymes excretion was monitored. Only minor changes in enzymuria were observed in the 10 and 30 mg/kg group. However, in the 50 mg/kg group, nephrotoxicity was evident by significant increase in the exc retion of N-acetyl-beta-D-glucosaminidase (NAG), glutamate dehydrogenase (G DH), and lactate dehydrogenase (LDH on day 2 of treatment. As chemotherapeu tic drug interaction with cyclosporine A (CyA) is thought to aggravate its nephrotoxicity, the effect of combined CyA (30 mg/kg) and the antibiotic ge ntamicin (50 mg/kg) for 5 days was investigated. Gentamicin alone caused a significant enzymuria, whilst co-treatment of rats with CyA gave rise to in creased changes in enzymuria on days 1 and 2, between the groups receiving gentamicin + vehicle and those receiving CyA + gentamicin. This was particu larly marked by significant changes in LDH excretion. In contrast these obs erved differences were not paralleled by changes in serum creatinine and ot her functional parameters. Treatment with gentamicin, appears to enhance Cy A nephrotoxicity, but only in the first 2 days, after this there was no sig nificant differences between the two groups. Our data suggest that urinary enzyme measurements could serve as a valuable non-invasive means of monitor ing renal performance in animals or humans who may be exposed to combinatio n of drugs. CyA is found not to potentiate the nephrotoxic effect of gentam icin in the animal model used in this study. It therefore appears safe to u se the combined therapy particularly in the treatment of transplant patient s.