| Abstrakt: |
Using a compound analgesic mixture, it was found that renal pathology could be produced in rats if the analgesic mixture was administered as a concentrated aqueous suspension, but that development of renal pathology was not favored by hot, dry environmental conditions. Determination of whole body total salicylate concentrations in rats and humans receiving various doses of aspirin revealed that twice daily doses of 24, 60 and 125 mg/kg aspirin in the rat were equivalent to human doses of 8, 20 and (approximately) 40 ordinary 325 mg aspirin tablets daily. These doses of aspirin were then employed in a subchronic study of the nephrotoxicity of aspirin in the rat using the experimental design which maximized the nephrotoxic effects of the compound analgesic mixture. Six groups of ten male and ten female rats received aspirin orally at doses of 24,60 or 125 mg/kg twice a day five days a week for 12 weeks. Two additional groups of ten male and ten female rats received only the vehicle, at a volume equivalent to that received by the high dose group, and served as controls. Four groups (one each, control, low, mid-, and high dose) were denied access to water for 16 hours daily overnight. No pathologic renal changes were observed in any of the rats. These findings are consistent with a growing body of evidence, from both animal and human studies, that aspirin alone does not produce analgesic nephropathy. |
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