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.