title: Nephrotoxicity induced by N-(3,5-dichlorophenyl)-3-hydroxysuccinamic acid in male and female Fischer 344 rats.
abstract: The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is a more potent nephrotoxicant in female rats than in males. Similarly, nephrotoxicant NDPS metabolites studied to date in male and female rats have also demonstrated gender differences, being twice as potent as nephrotoxicants in females as in males. The purpose of this study was to examine the nephrotoxic potential of N-(3,5-dichlorophenyl)-3-hydroxysuccinimide (3-NDHSA) in male and female Fisher 344 rats to determine if gender differences in nephrotoxic potential also exist for this metabolite. Rats (four per group) were administered a single intraperitoneal (i.p.) injection of 3-NDHSA (0.1, 0.2 or 0.4 mmol kg(-1)) or vehicle, and renal function was monitored at 24 and 48 h. 3-NDHSA 0.1 mmol kg(-1) did not induce nephrotoxicity in male or female rats. In male rats, 3-NDHSA 0.2 mmol kg(-1) induced mild nephrotoxicity seen as diuresis and transient, mild proteinuria. However, 3-NDHSA 0.4 mmol kg(-1) induced marked nephrotoxicity. In female rats, 3-NDHSA 0.2 mmol kg(-1) induced mild nephrotoxicity, as evidenced by transient diuresis and proteinuria. As in males, 3-NDHSA 0.4 mmol kg(-1) induced marked nephrotoxicity. These results indicate that, unlike NDPS and other nephrotoxic NDPS metabolites, 3-NDHSA does not exhibit gender differences in nephrotoxic potential. In addition, in comparison with NDPS and other nephrotoxic NDPS metabolites, 3-NDHSA is a less potent nephrotoxicant that NDHS or 2-NDHSA and similar to NDPS in nephrotoxic potential in male rats.
authors.affiliation: Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA. rankin@marshall.edu
authors.forename: Gary O
authors.initials: GO
authors.lastname: Rankin
authors.forename: Suk-kil
authors.initials: SK
authors.lastname: Hong
authors.forename: Dianne K
authors.initials: DK
authors.lastname: Anestis
mesh_terms: D000818:Animals; D004231:Diuresis / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000139:chemically induced / Q000503:physiopathology; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors; D013388:Succinimides / Q000633:toxicity*
chemical_list: D005659:Fungicides, Industrial; D013388:Succinimides; C007352:N-(3,5-dichlorophenyl)succinimide