N-(3,5-Dichlorophenyl)succinimide nephrotoxicity in the Fischer-344 rat

Abstract

The nephrotoxic potential of N-(3,5-dichlorophenyl)succinimide (NDPS) was examined, in male Fischer-344 rats. Rats were administered NDPS (0.1, 0.2, 0.4 or 1.0 mmol/kg intraperitoneally (i.p.) or sesame oil (2.5 ml/kg, i.p.), and renal function was monitored at 24 and 48 h. NDPS (0.1 mmol/kg) stimulated organic ion uptake at 48 h. NDPS (0.2 mmol/kg produced diuresis but did not alter blood urea nitrogen (BUN), kidney weight or organic ion uptake by renal cortical slices at 48 h. High-dose NDPS (0.4 and 1.0 mmol/kg) administration produced diuresis, decreased accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA), increased BUN and kidney weight and caused acute tubular necrosis. At 24 h, NDPS (0.2 mmol/kg) decreased uptake of PAH and TEA and tended to increase BUN. These results are similar to previous reports of NDPS-induced nephrotoxicity in Sprague-Dawley rats and suggest that either rat model would be suitable for future studies on the mechanism(s) of NDPS-induced nephropathy.