Renal effects of N-(3,5-disubstitutedphenyl)-succinimides in the Fischer 344 rat.
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.
Rankin
G O
GO
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310.
Teets
V J
VJ
Shih
H
H
Beers
K W
KW
Nicoll
D W
DW
Anestis
D K
DK
Brown
P I
PI
Hubbard
J L
JL
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
D013388:Succinimides