N-（3,5-二氯苯基）戊二酰亚胺和N-（3,5-二氯苯基）戊酰胺酸对费希尔344大鼠的肾毒性潜力。

Nephrotoxic potential of N-(3,5-dichlorophenyl)glutarimide and N-(3,5-dichlorophenyl)glutaramic acid in Fischer 344 rats.

作者信息

Kellner-Weibel G L, Tchao R, Harvison P J

机构信息

Department of Chemistry, Philadelphia College of Pharmacy and Science, PA 19104-4495, USA.

出版信息

Toxicol Lett. 1995 Oct;80(1-3):123-9. doi: 10.1016/0378-4274(95)03386-y.

DOI:10.1016/0378-4274(95)03386-y

PMID:7482579

Abstract

The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) produces kidney damage in rats. Although many NDPS analogues have been screened as possible nephrotoxicants, the one-carbon homologue, N-(3,5-dichlorophenyl)glutarimide (NDPG), has not been evaluated. This study examined the nephrotoxic potential of NDPG and a putative metabolite, N-(3,5-dichlorophenyl)glutaramic acid (NDPGA). Male Fischer 344 rats (N = 3-4 per group) were administered a single i.p. injection in corn oil of NDPG or NDPGA (0.4 or 1.0 mmol/kg), NDPS (0.4 mmol/kg), or corn oil alone. Renal function was monitored for 48 h. In contrast to NDPS, NDPG and NDPGA did not significantly alter renal function or kidney morphology when compared to corn oil-treated controls. These experiments show that replacement of the succinimide ring in NDPS with a glutarimide ring abolishes toxicity.

摘要

农用杀菌剂N-(3,5-二氯苯基)琥珀酰亚胺(NDPS)可导致大鼠肾脏损伤。尽管已筛选了许多NDPS类似物作为潜在的肾毒物，但一碳同系物N-(3,5-二氯苯基)戊二酰亚胺(NDPG)尚未得到评估。本研究检测了NDPG及其一种假定代谢产物N-(3,5-二氯苯基)戊二酸(NDPGA)的肾毒性潜力。将雄性Fischer 344大鼠(每组N = 3 - 4只)经腹腔注射给予NDPG或NDPGA(0.4或1.0 mmol/kg)、NDPS(0.4 mmol/kg)或仅玉米油。监测肾功能48小时。与NDPS不同，与玉米油处理的对照组相比，NDPG和NDPGA并未显著改变肾功能或肾脏形态。这些实验表明，用戊二酰亚胺环取代NDPS中的琥珀酰亚胺环可消除毒性。