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

Research Project

Project/Area Number	05671902
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	応用薬理学・医療系薬学
Research Institution	Jichi Medical School
Principal Investigator	FUJIMURA Akio Jich Medical School,, 医学部, 教授 (90156901)
Project Period (FY)	1993 – 1994
Project Status	Completed (Fiscal Year 1994)
Budget Amount *help	¥2,100,000 (Direct Cost: ¥2,100,000) Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000) Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
Keywords	ANP / sinorphan / cyclosporin / amikacin / nephrotoxicity
Research Abstract	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.