EFFECT OF DIMETHYL-SULFOXIDE ON N-(3,5-DICHLOROPHENYL) SUCCINIMIDE (NDPS) AND NDPS METABOLITE NEPHROTOXICITY

Dimethyl sulfoxide (DMSO) is frequently used as a solvent to assist in dissolving compounds which are not readily soluble in other injection vehicles. The purpose of this study was to determine the suitability of DMSO as a vehicle for administering the nephrotoxicant, N-(3,5-dich lorophenyl)succinimide, (NDPS) and two nephrotoxicant NDPS metabolites , N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5-dichlo rophenyl)-2-hydroxysuccinamic acid (NDHSA). Male Fischer 344 rats (4/g roup) were administered a single intraperitoneal injection of NDPS (0. 4 or 0.8 mmol/kg), NDHS (0.1 or 0.2 mmol/kg), or NDHSA (0.1 or 0.2 mmo l/kg) dissolved in 25% DMSO in sesame oil or 100% sesame oil(2.5 ml/kg ), while control rats received vehicle only. Renal function was then m onitored at 24 and 48 h. Including DMSO in the vehicle markedly attenu ated NDPS 0.4 mmol/kg-induced nephrotoxicity and reduced NDPS 0.8 mmol /kg-induced renal effects. Thus, the magnitude of the attenuating effe ct of DMSO depended in part on the nephrotoxicant dose of NDPS. In add ition, NDHS nephrotoxicity was not altered by DMSO and only slight eff ects on NDHSA nephrotoxicity were observed. These results suggest that DMSO is capable of attenuating NDPS nephrotoxicity, and that the prim ary mechanism of this interaction might be due to an inhibition of the biotransformation of NDPS to NDHS.