Protective Effects of KW-3902, an Adenosine A1-Receptor Antagonist, Against the Nephropathy Induced by Repeated Administration of Cisplatin in Rats.

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We investigated the possible renal protective effect of KW-3902 (8-(noradamantan-3-yl)-1 ,3-dipropyl-xanthine), a novel adenosine A1-receptor antagonist, against the nephropathy induced by repeated administration of cisplatin (2.5 mg/kg, i.v., once weekly for 6 weeks) in rats. Repeated administration of cisplatin increased serum creatinine (S-CRE) and urea nitrogen (S-UN), and decreased creatinine clearance (CL.CRE) for 1 to 6 weeks. Administration of KW-3902 (0.01 and 0.1 mg/kg, i.v. once weekly for 6 weeks) 5 minutes before each cisplatin treatment significantly improved these changes. On the 5th day after the final administration of cisplatin, KW-3902 significantly improved the increase in kidney weight and the decrease in reabsorption rate of water and sodium. Moreover, on the 5th day after the final administration of cisplatin, tubular lesions, such as tubular necrosis and cystic dilatation of tubules were diffusely observed in the renal cortex in the cisplatin administered group. KW-3902 tended to improve these lesions. This study suggests that pretreatment of KW-3902 could protect against renal lesions caused by repeated administration of cisplatin, which is similar to clinical therapy schedule.
日本毒性病理学会の論文