NEPHROTOXICITY OF CYCLOSPORINE A AND CYCLOSPORINE G IN A RAT MODEL1

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Abstract
Cyclosporine G (CsG) like cyclosporine A (CsA) is a cyclic endecapeptide where the alpha-amino butyric acid residue in position 2 is replaced by norvaline. We studied the effects of both drugs on renal function in a nontransplant rat model to avoid the additional variable of rejection. Age- and weight-matched pairs of male Sprague-Dawley rats were treated subcugtaneously for 21 days with a daily dose of 25 mg/kg bw of either powdered CsA or CsG dissolved in 1 ml of olive oil. A control group (C) received olive oil only. Blood pressure (BP) and creatinine (Cr) were measured on days 0, 7, 14, and 21. On day 22, animals were weighted, aqnesthetized, and glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured using C14 inulin and 3R pareAminohippuric acid, respectively, Renal plasma flow and glomerular filtration rate were unaltered in CsG-treated animals compared to controls but significantly reduced in CsA-treated animals. Histologically, vacuolization and microcalcification were seen in significantly greater frequency among the CsA-treated animals. CsG with lesser nephrotoxic potential may prove to be of use in maintenance of therapy of transplants as well as selected autoimmune disorders.