We investigated possible renal protective and
therapeutic effects of
KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a novel and potent
adenosine A1-receptor antagonist, on
cisplatin-induced
acute renal failure (ARF). ARF was induced in rats by a single injection of
cisplatin-induced
acute renal failure (ARF). ARF was induced in rats by a single injection of
cisplatin (5 mg/kg, i.v.). Prophylactic treatment with
KW-3902 (0.01-1 mg/kg, p.o., twice a day) significantly attenuated the increases of serum
creatinine (S-CRE) and
urea nitrogen (S-UN) induced by
cisplatin. On the other hand, neither
furosemide nor
trichlormethiazide showed any ameliorating effects against the
cisplatin-induced ARF. In the clearance study, the
cisplatin-treatment induced marked decreases of glomerular filtration rate (GFR), renal plasma flow (RPF), and reabsorptions of water,
sodium and
potassium at tubular sites, in comparison with those in untreated normal rats.
KW-3902 (0.1 mg/kg, p.o., twice a day) significantly improved these deteriorated glomerular and tubular functions. In the rats with established
cisplatin-induced ARF,
KW-3902 ameliorated the
cisplatin-induced reductions of GFR, RPF, and reabsorptions of water,
sodium and
potassium at tubular sites. These results suggest that activation of
adenosine A1-receptors is involved in the pathogenesis of
cisplatin-induced ARF. The
adenosine A1-receptor antagonist may be useful for the treatment of
cisplatin-induced ARF.