Renal effects of N-(3,5-disubstitutedphenyl)-succinimides in the fischer 344 rat

✍ Scribed by Gary O. Rankin; Vonda J. Teets; Hsiencheng Shih; Kelly W. Beers; Derek W. Nicoll; Dianne K. Anestis; Patrick I. Brown; John L. Hubbard

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 549 KB
• Volume: 12
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.2550120311

✦ Synopsis

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-') or vehicle, and the renal function was monitored for 48 h. Only N-(3,5-dichlorophenyI)succinimide (0.4 or 1.0 mmol kg-I) induced marked changes in renal function. Urine volume, BUN concentration and proteinuria were increased following N-(3,5-dinitrophenyl)succinimide (1.0 mmol kg-') 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 3and 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.