Protective effects of KW-3902, a novel adenosine A1-receptor antagonist, against gentamicin-induced acute renal failure in rats.
We investigated the possible renal protective effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), an adenosine A1-receptor antagonist, against gentamicin (GM)-induced acute renal failure (ARF) in rats. ARF was induced by subcutaneous injection of GM at 80 mg/kg/day for 12 days. KW-3902 (0.001-0.1 mg/kg, p.o., twice daily) attenuated the increases of serum creatinine and urea nitrogen and the decrease of creatinine clearance in rats treated with GM. In contrast, furosemide and trichlormethiazide aggravated the GM-induced nephrotoxicity. These results suggest that KW-3902 can ameliorate the GM-induced ARF and that endogenous adenosine may be involved in GM-induced ARF via the adenosine A1-receptor.
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
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Yao
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Kusaka
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Sato
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Karasawa
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005839:Gentamicins / Q000008:administration & dosage / Q000633:toxicity*; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D014237:Trichlormethiazide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D005839:Gentamicins; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C073525:rolofylline; D005665:Furosemide; D014237:Trichlormethiazide