二甲基亚砜对N-(3,5-二氯苯基)琥珀酰亚胺（NDPS）及其代谢产物肾毒性的影响。

Effect of dimethyl sulfoxide on N-(3,5-dichlorophenyl)succinimide (NDPS) and NDPS metabolite nephrotoxicity.

作者信息

Rankin G O, Beers K W, Nicoll D W, Anestis D K, Ball J G, Valentovic M A, Brown P I

机构信息

Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25704-9388, USA.

出版信息

Toxicology. 1995 Jun 26;100(1-3):79-88. doi: 10.1016/0300-483x(95)93709-d.

DOI:10.1016/0300-483x(95)93709-d

PMID:7624885

Abstract

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-dichlorophenyl)succinimide, (NDPS) and two nephrotoxicant NDPS metabolites, N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (NDHSA). Male Fischer 344 rats (4/group) 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 mmol/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 monitored at 24 and 48 h. Including DMSO in the vehicle markedly attenuated NDPS 0.4 mmol/kg-induced nephrotoxicity and reduced NDPS 0.8 mmol/kg-induced renal effects. Thus, the magnitude of the attenuating effect of DMSO depended in part on the nephrotoxicant dose of NDPS. In addition, NDHS nephrotoxicity was not altered by DMSO and only slight effects on NDHSA nephrotoxicity were observed. These results suggest that DMSO is capable of attenuating NDPS nephrotoxicity, and that the primary mechanism of this interaction might be due to an inhibition of the biotransformation of NDPS to NDHS.

摘要

二甲基亚砜（DMSO）常被用作溶剂，以帮助溶解不易溶于其他注射载体的化合物。本研究的目的是确定DMSO作为给药肾毒性剂N-（3,5-二氯苯基）琥珀酰亚胺（NDPS）以及两种肾毒性剂NDPS代谢物N-（3,5-二氯苯基）-2-羟基琥珀酰亚胺（NDHS）和N-（3,5-二氯苯基）-2-羟基琥珀酰胺酸（NDHSA）载体的适用性。将雄性Fischer 344大鼠（每组4只）腹腔注射一次溶解于25% DMSO的芝麻油或100%芝麻油（2.5 ml/kg）中的NDPS（0.4或0.8 mmol/kg）、NDHS（0.1或0.2 mmol/kg）或NDHSA（0.1或0.2 mmol/kg），而对照大鼠仅接受载体。然后在24小时和48小时监测肾功能。载体中加入DMSO可显著减轻0.4 mmol/kg的NDPS诱导的肾毒性，并降低0.8 mmol/kg的NDPS诱导的肾脏效应。因此，DMSO的减轻作用程度部分取决于NDPS的肾毒性剂量。此外，DMSO未改变NDHS的肾毒性，仅观察到对NDHSA肾毒性有轻微影响。这些结果表明，DMSO能够减轻NDPS的肾毒性，这种相互作用的主要机制可能是由于抑制了NDPS向NDHS的生物转化。