2-AMINOPHENOL AND 4-AMINOPHENOL TOXICITY IN RENAL SLICES FROM SPRAGUE-DAWLEY AND FISCHER-344 RATS

This study examined differences in toxicity between 2- and C-aminophen ol using a renal cortical slice model. Renal cortical slice toxicity f or 2- and 4-aminophenol was also monitored in tissue from Sprague-Dawl ey and Fischer 344 (F344) rats in order to determine potential strain differences for aminophenol toxicity. Renal cortical slices from Sprag ue-Dawley and F344 rats (age 50-65 d) were isolated and incubated for 15-120 min with 0-1 mM 2- or 4-aminophenol at 37 degrees C under an ox ygen atmosphere. Elevations in lactate dehydrogenase (LDH) leakage fro m renal cortical slices occurred at lower concentrations of 4-aminophe nol than of 2-aminophenol from both strains of rats. Total glutathione levels were more markedly decreased by 4-aminophenol than by 2-aminop henol in renal slices from both strains. LDH release was elevated by I mM 2-aminophenol in renal slices from F344 rats, but values were comp arable between control and treated in the renal slices from Sprague-Da wley rats. 4-Aminophenol was slightly more toxic to renal slices from F344 than from Sprague-Dawley rats. LDH release was increased, relativ e to controls, by 0.1 mM in the F344 rats group compared to 0.25 mM in the Sprague-Dawley group. Strain differences were not apparent when c omparisons were made of total glutathione levels or rate-limiting subs trates of gluconeogenesis. These results indicated that strain differe nces in toxicity were detected between Sprague-Dawley and F344 rat str ains. Based on LDH release, renal cortical slices obtained from age-ma tched F344 rats were slightly more susceptible than Sprague-Dawley rat s to toxicity by 2- and 4-aminophenol.