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 excretion of N-acetyl-beta-D-glucosaminidase (NAG), glutamate dehydrogenase (GDH), and lactate dehydrogenase (LDH on day 2 of treatment. As chemotherapeutic drug interaction with cyclosporine A (CyA) is thought to aggravate its nephrotoxicity, the effect of combined CyA (30 mg/kg) and the antibiotic gentamicin (50 mg/kg) for 5 days was investigated. Gentamicin alone caused a significant enzymuria, whilst co-treatment of rats with CyA gave rise to increased changes in enzymuria on days 1 and 2, between the groups receiving gentamicin+vehicle and those receiving CyA+gentamicin. This was particularly marked by significant changes in LDH excretion. In contrast these observed differences were not paralleled by changes in serum creatinine and other functional parameters. Treatment with gentamicin, appears to enhance CyA nephrotoxicity, but only in the first 2 days, after this there was no significant differences between the two groups. Our data suggest that urinary enzyme measurements could serve as a valuable non-invasive means of monitoring renal performance in animals or humans who may be exposed to combination of drugs. CyA is found not to potentiate the nephrotoxic effect of gentamicin in the animal model used in this study. It therefore appears safe to use the combined therapy particularly in the treatment of transplant patients.
Fashola
T O
TO
Department of Biochemistry, Kings College, London, UK.
Obatomi
D K
DK
Plummer
D T
DT
D000118:Acetylglucosaminidase / Q000187:drug effects / Q000652:urine; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004798:Enzymes / Q000187:drug effects / Q000652:urine*; D005839:Gentamicins / Q000008:administration & dosage / Q000633:toxicity*; D005969:Glutamate Dehydrogenase / Q000187:drug effects / Q000652:urine; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000652:urine; D008297:Male; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D004798:Enzymes; D005839:Gentamicins; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007770:L-Lactate Dehydrogenase; D005969:Glutamate Dehydrogenase; D000118:Acetylglucosaminidase