Preventive effect of an enkephalinase inhibitor on drug-induced nephrotoxicity.

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Nephrotoxicity is one of adverse effects observed during treatment with cyclosporin, a potent immunosuppressive agent, and amikacin, an aminoglycoside antibiotics. The present study was undertaken to examine whether sinorphan, an enkephalinase inhibitor, might prevent a cyclosporin-or amikacin-induced nephrotoxicity. Male Wistar rats received cyclosporin (50mg/kg・day, orally) or amikacin (250mg/kg・day, intraperitoneally) with or without sinorphan (50mg/kg・day, orally) for 14 days.The reduction in creatinine clearance and the elevations in urinary NAG excretion and plasma renin activity were observed in rats treated with cyclosporin or amikacin alone. Morphological changes in renal tissue were demostrated in these animals. However, the degree of the drug-induced renal damage was lessened in rats treated with both the nephrotoxic agent and sinorphan. These results suggest that sinorphan might prevent the nephrotoxicity caused by cyclosporin and amikacin.