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.
N-(3,5-Dichlorophenyl)succinimide (NDPS) is an agricultural fungicide that induces nephrotoxicity as its major toxicity. NDPS is also a more potent nephrotoxicant in female than in male rats. The purpose of this study was to examine the nephrotoxic potential of the two NDPS metabolites N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA) in age-matched male and female Fischer 344 rats to determine if gender differences exist for the nephrotoxicity induced by the two NDPS metabolites. Rats (4 per group) were administered a single intraperitoneal (ip) injection of NDHS or 2-NDHSA (0.025 or 0.05 mmol/kg) or vehicle, and renal function was monitored for 48 h. Neither compound induced significant nephrotoxicity in male rats at the doses tested. However, in female rats both metabolites induced marked nephrotoxicity at the 0.05 mmol/kg dose level, and treatment with 0.025 mmol/kg 2-NDHSA induced some changes in renal function (transient diuresis, transient proteinuria, decreased organic ion accumulation). Little effect on renal function was induced in females by treatment with 0.025 mmol/kg NDHS. At toxic levels in female rats, the renal lesions were located primarily in the S2 and S3 segments of the proximal tubule. These results indicate that, like the parent compound, gender differences exist in the nephrotoxic potential of NDHS and 2-NDHSA. The results also suggest that in females, as in males, NDPS nephrotoxicity is mediated via NDHS and/or 2-NDHSA. However, it is not clear if the ultimate nephrotoxicant species following NDPS exposure is different in males and females or if the same ultimate nephrotoxicant species is produced in both species but handled differently by male and female kidneys. Thus, further studies are needed to determine the exact nature of the ultimate nephrotoxicant species and the mechanisms of the observed gender differences.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.