Onset of and recovery from acute N-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity in Sprague-Dawley rats.
The time course for the onset of N-(3,5-dichlorophenyl)succinimide (NDPS)-induced nephrotoxicity was studied in male Sprague-Dawley rats. The ability of rats to recover from a single nephrotoxic dose (100 or 200 mg/kg) of NDPS also was examined. One hour following NDPS administration (200 mg/kg, i.p.), p-aminohippurate (PAH) accumulation by renal cortical slices was decreased 51%. Changes in renal morphology, proteinuria, hematuria, and diuresis were observed at 3 h. Renal damage at 6 h was similar to that seen at 24 h with tubular necrosis greater than that observed at 3 h and some lumina plugged with PAS+ material. Accumulation of both PAH and tetraethylammonium (TEA) by renal cortical slices was decreased; and proteinuria, hematuria, and polyuria were increased at 6 h and 24 h. Blood urea nitrogen (BUN) was not increased until 24 h. Renal function began to return to normal in rats receiving NDPS (100 mg/kg, i.p.) by 48 h, and functional recovery was complete by 168 h, although slight morphological changes were still evident. However, not all rats receiving NDPS (200 mg/kg, i.p.) recovered by 168 h, and some rats (3 of 7) died of renal failure between 96 h and 168 h. Widespread tubular necrosis and increased kidney weight were also present in this group at 168 h. Thus, NDPS-induced nephrotoxicity was evident by 1 h, established by 6 h and maximum between 24 h and 48 h. Recovery from NDPS-induced nephropathy was found to be dose-dependent, and incomplete in some animals at a dose of 200 mg/kg.
D000818:Animals; D001806:Blood Urea Nitrogen; D004231:Diuresis / Q000187:drug effects; D006417:Hematuria / Q000139:chemically induced; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects; D008297:Male; D009929:Organ Size; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D013388:Succinimides / Q000633:toxicity*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism; D013997:Time Factors; D010130:p-Aminohippuric Acid / Q000378:metabolism
D013388:Succinimides; D013757:Tetraethylammonium Compounds; C007352:N-(3,5-dichlorophenyl)succinimide; D019789:Tetraethylammonium; D010130:p-Aminohippuric Acid