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Renal effects of N ‐(3,5‐disubstitutedphenyl)‐succinimides in the fischer 344 rat
Author(s) -
Rankin Gary O.,
Teets Vonda J.,
Shih Hsiencheng,
Beers Kelly W.,
Nicoll Derek W.,
Anestis Dianne K.,
Brown Patrick I.,
Hubbard John L.
Publication year - 1992
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550120311
Subject(s) - succinimide , nephrotoxicity , succinimides , chemistry , renal function , intraperitoneal injection , kidney , endocrinology , medicine , halogen , pharmacology , toxicity , biochemistry , organic chemistry , alkyl
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 nephrotoxicarrts 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 atthe 3‐ and 5‐positioiis of the phenyl nag 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.