Effect of the adenosine antagonist 8-phenyltheophylline on glycerol-induced acute renal failure in the rat

Abstract

8-Phenyltheophylline (8-PT)(10 mg kg-1) or its vehicle(1 ml kg-1) were administered intravenously or intraperitoneally twice daily over 48 h to rats with acute renal failure (ARF) induced by intramuscular (i.m.) injection of glycerol. Rats treated with 8-PT i.v. had significantly lower plasma urea and creatinine levels at 24 and 48 h compared to untreated animals. The vehicle also reduced plasma urea and creatinine when compared to untreated controls. However, plasma urea levels in 8-PT-treated rats were significantly lower than in vehicle-treated animals at 24 and 48 h after both i.v. and i.p. administration. Plasma creatinine concentrations also tended to be lower in the 8-PT-treated group. [3H]-inulin clearance at 48 h after i.m. glycerol was significantly greater in rats dosed i.p. with 8-PT compared to either untreated or vehicle treated rats. Examination of kidneys taken from rats 48 h after i.m. glycerol showed that 8-PT treatment significantly reduced renal damage and kidney weight compared to the untreated or vehicle-treated groups. In a 7 day study all the rats which received 8-PT i.p. survived whilst in the vehicle and untreated groups the mortality rates were 12 and 21% respectively. In a separate series of experiments 8-PT (10 mg kg-1, i.v. or i.p.) was found to antagonize adenosine-induced bradycardia in conscious rats for up to 5 h. There is no clear explanation for the partial protection afforded by the vehicle but it may be related to either its alkalinity or an osmotic effect produced by the polyethylene glycol component. 9 The protective effect of 8-PT in rats with ARF was probably the result of adenosine antagonism.