Format

Send to

Choose Destination
See comment in PubMed Commons below
Toxicology. 1997 Feb 14;117(1):73-83.

The effect of aromatic fluorine substitution on the nephrotoxicity and metabolism of N-(3,5-dichlorophenyl)succinimide in Fischer 344 rats.

Author information

1
Department of Chemistry, Philadelphia College of Pharmacy and Science, PA 19104-4495, USA.

Abstract

N-(3,5-Difluorophenyl)succinimide (DFPS) is a non-toxic analogue of the nephrotoxic fungicide N-(3,5-dichlorophenyl)succinimide (NDPS). Although NDPS must be metabolized to produce renal damage, the metabolic fate of DFPS is unknown. These studies were therefore designed to examine the nephrotoxic potential of putative DFPS metabolites and to determine if DFPS is metabolized differently from NDPS. Male Fischer-344 rats were administered (1.0 mmol/kg. i.p. in corn oil) DFPS, N-(3,5-difluorophenyl)succinamic acid (DFPSA), N-(3,5-difluorophenyl)-2-hydroxysuccinimide (DFHS), N-(3,5-difluorophenyl)-2- or -3-hydroxysuccinamic acids (2- and 3-DFHSA, respectively), N-(3,5-difluoro-4-hydroxyphenyl)succinimide (DFHPS). N-(3,5-difluoro-4-hydroxyphenyl) succinamic acid (DFHPSA) or corn oil only (1.2 ml/kg). Although some of the compounds produced changes in renal function and histology, these alterations were not indicative of irreversible kidney damage. DFPSA, 2-DFHSA, 3-DFHSA and DFHPSA were detected in the urine of rats 3 h after administration of 0.2 mmol/kg [14C]DFPS. The same metabolites were produced by isolated rat hepatocytes, but not by renal proximal tubule cells. Formation of the oxidative metabolites in vitro was prevented by the cytochrome P450 inhibitor 1-aminobenzotriazole. It appears that DFPS undergoes hepatic biotransformation similar to NDPS and that some of its metabolites have reversible effects on renal proximal tubules.

PMID:
9020201
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center