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

Abstract

This study examined differences in toxicity between 2- and 4-aminophenol using a renal cortical slice model. Renal cortical slice toxicity for 2- and 4-aminophenol was also monitored in tissue from Sprague-Dawley and Fischer 344 (F344) rats in order to determine potential strain differences for aminophenol toxicity. Renal cortical slices from Sprague-Dawley and F344 rats (age 50-65 d) were isolated and incubated for 15-120 min with 0-1 m M 2- or 4-aminophenol at 37 C under an oxygen atmosphere. Elevations in lactate dehydrogenase (LDH) leakage from renal cortical slices occurred at lower concentrations of 4-aminophenol than of 2-aminophenol from both strains of rats. Total glutathione levels were more markedly decreased by 4-aminophenol than by 2-aminophenol in renal slices from both strains. LDH release was elevated by 1 m M 2-aminophenol in renal slices from F344 rats, but values were comparable between control and treated in the renal slices from Sprague-Dawley rats. 4-Aminophenol was slightly more toxic to renal slices from F344 than from Sprague-Dawley rats. LDH release was increased, relative to controls, by 0.1 m M in the F344 rats group compared to 0.25 m M in the Sprague-Dawley group. Strain differences were not apparent when comparisons were made of total glutathione levels or rate-limiting substrates of gluconeogenesis. These results indicated that strain differences in toxicity were detected between SpragueDawley and F344 rat strains. Based on LDH release, renal cortical slices obtained from age-matched F344 rats were slightly more susceptible than Sprague-Dawley rats to toxicity by 2- and 4-aminophenol.