Structure-nephrotoxicity relationships for para-substituted N-phenylsuccinimides in Sprague-Dawley and Fischer 344 rats. 1985

D J Yang, and E P Lahoda, and P I Brown, and G O Rankin

N-(3,5-Dichlorophenyl)succinimide (NDPS) has proven to be one of the most nephrotoxic compounds of a series of N-(halophenyl)succinimides. Previous studies in our laboratory have demonstrated that chlorine content and position on the phenyl ring are important determinants for NDPS-induced nephrotoxicity. The purpose of this study was to investigate the relationship between the electron donating or withdrawing nature of phenyl group substituents and the nephrotoxic potential of the corresponding fungicides. Rats were administered a para-substituted N-phenylsuccinimide (0.4 or 1.0 mmol/kg, i.p.) or sesame oil (2.5 ml/kg, i.p.), and renal function was monitored at 24 h and 48 h. In Sprague-Dawley rats, a clear nephrotoxicity was produced by NDPS. Weak nephrotoxicity was produced by N-(4-tert-butylphenyl)succinimide (NBPS). NDPS also was the most nephrotoxic compound in Fischer 344 rats, while weak nephrotoxicity was produced by NBPS. Lipophilic character (e.g. partition coefficient) did not correlate with acute nephrotoxicity in either rat strain. These results also indicate that there is a no correlation between the electronic nature of the phenyl substituents and resulting nephrotoxicity.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007674 Kidney Diseases Pathological processes of the KIDNEY or its component tissues. Disease, Kidney,Diseases, Kidney,Kidney Disease
D007687 Kidney Tubules, Proximal The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE. Proximal Kidney Tubule,Proximal Renal Tubule,Kidney Tubule, Proximal,Proximal Kidney Tubules,Proximal Renal Tubules,Renal Tubule, Proximal,Renal Tubules, Proximal,Tubule, Proximal Kidney,Tubule, Proximal Renal,Tubules, Proximal Kidney,Tubules, Proximal Renal
D008297 Male Males
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001806 Blood Urea Nitrogen The urea concentration of the blood stated in terms of nitrogen content. Serum (plasma) urea nitrogen is approximately 12% higher than blood urea nitrogen concentration because of the greater protein content of red blood cells. Increases in blood or serum urea nitrogen are referred to as azotemia and may have prerenal, renal, or postrenal causes. (From Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984) BUN,Nitrogen, Blood Urea,Urea Nitrogen, Blood
D004231 Diuresis An increase in the excretion of URINE. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Diureses
D005659 Fungicides, Industrial Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc. Industrial Fungicides
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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