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 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 mM 2- or 4-aminophenol at 37 degrees 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 mM 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 mM in the F344 rats group compared to 0.25 mM 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 Sprague-Dawley 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.
Department of Pharmacology, Marshall University School of Medicine, Huntington, West Virginia, USA. valentov@marshall.edu
M A
MA
Valentovic
J G
JG
Ball
D000627:Aminophenols / Q000633:toxicity*; D000818:Animals; D005943:Gluconeogenesis / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D000627:Aminophenols; C027667:2-aminophenol; D005978:Glutathione; C026729:4-aminophenol