title: Renal effects of N-(3,5-disubstitutedphenyl)-succinimides in the Fischer 344 rat.
abstract: Previous studies have demonstrated the importance of substitution at the 3- and 5-positions of the phenyl ring in N-phenylsuccinimides for the production of nephrotoxicants in this series of compounds. The purpose of this study was to determine if the electronic nature of the 3,5-substituents is an important determinant for nephrotoxic potential. Male Fischer 344 rats (four rats per group) were administered a single intraperitoneal injection of a succinimide (0.4 or 1.0 mmol kg-1) or vehicle, and the renal function was monitored for 48 h. Only N-(3,5-dichlorophenyl)succinimide (0.4 or 1.0 mmol kg-1) induced marked changes in renal function. Urine volume, BUN concentration and proteinuria were increased following N-(3,5-dinitrophenyl)succinimide (1.0 mmol kg-1) treatment but other renal parameters and renal morphology were unchanged in this treatment group. These results indicate that the presence of halogen atoms at the 3- and 5-positions of the phenyl ring in N-phenylsuccinimides is more important for nephrotoxic potential than the presence of non-halogen substituents. The reason why halogen substitution is an important determinant for N-phenylsuccinimide nephrotoxicity is unknown.
authors.affiliation: Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310.
authors.forename: G O
authors.initials: GO
authors.lastname: Rankin
authors.forename: V J
authors.initials: VJ
authors.lastname: Teets
authors.forename: H
authors.initials: H
authors.lastname: Shih
authors.forename: K W
authors.initials: KW
authors.lastname: Beers
authors.forename: D W
authors.initials: DW
authors.lastname: Nicoll
authors.forename: D K
authors.initials: DK
authors.lastname: Anestis
authors.forename: P I
authors.initials: PI
authors.lastname: Brown
authors.forename: J L
authors.initials: JL
authors.lastname: Hubbard
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D013388:Succinimides / Q000633:toxicity*; D014563:Urodynamics / Q000187:drug effects
chemical_list: D013388:Succinimides