Amelioration of glycerol-induced acute renal failure in the rat with 8-phenyltheophylline: timing of intervention

The importance of timing and duration of 8-phenyltheophylline (8-PT) administration in determining its beneficial action in glycerol-induced acute renal failure (ARF) was investigated by examining the effects of a single dose of 8-PT given immediately following (0 h) glycerol injection and at 1 and 3 h after glycerol injection. 8-PT when given at 0 h significantly lowered plasma urea and creatinine concentrations and significantly increased inulin clearance when compared both to untreated animals and those that received the vehicle for the drug. By contrast, 8-PT when administered at 1 h afforded no protective effect on renal function and, when injected at 3 h, the only significant effect was lowered plasma creatinine levels when compared to untreated rats; at this latter time it did not lower plasma urea levels or improve inulin clearance. None of the 8-PT injections attenuated the increase in kidney weight associated with ARF or reduced the kidney damage as assessed by histological examination. The results show that a single administration of 8-PT made immediately following glycerol injection can ameliorate the biochemical and functional indices of impaired renal function, but does not produce an improvement in kidney morphology.