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多种抗氧化剂对通过吸入或经皮途径给予小鼠的硫芥毒性的保护作用。

Protective effect of various antioxidants on the toxicity of sulphur mustard administered to mice by inhalation or percutaneous routes.

作者信息

Kumar O, Sugendran K, Vijayaraghavan R

机构信息

Division of Pharmacology and Toxicology, Defence Research and Development Establishment, 474002, Gwalior, India.

出版信息

Chem Biol Interact. 2001 Mar 14;134(1):1-12. doi: 10.1016/s0009-2797(00)00209-x.

DOI:10.1016/s0009-2797(00)00209-x
PMID:11248218
Abstract

Protective effect of various antioxidants, trolox (water soluble analogue of vitamin E), quercetin (bioflavonoid) and glutathione reduced (GSH), was studied following sulphur mustard (SM) intoxication. SM, a blistering agent was administered to Swiss albino female mice through inhalation (1 LC50=42.3 mg/m3 for 1 h duration; 14 days observation for mortality) and percutaneous (1 LD50=154.7 mg/kg; 7 days observation for mortality) routes. The antioxidants were administered three times at the dose of trolox, 500 microg/kg; quercetin, 5 mg/kg and GSH, 400 mg/kg body weight by intraperitoneal injection, one immediately following SM exposure, then once each day for 2 days after SM treatment. The effect of antioxidants on survival, markers of oxidative damage and purine metabolites was investigated. Survival study animals were observed for 14 days. Oxidative markers (in blood, liver and lung) and purine metabolites (in blood and urine) were investigated 72 h after SM treatment. Survival time increased significantly following trolox and quercetin treatments through the inhalation route. Significant decrease in GSH and increase in the level of malondialdehyde (MDA) indicated oxidative damage to liver and lung tissues following SM inhalation and percutaneous exposure. Blood and urinary uric acid, end product of purine metabolism showed an increased following both routes of exposures. The antioxidants, trolox and quercetin protected the liver and lung tissues from oxidative damage caused by SM exposure through inhalation and percutaneous routes. This study showed that antioxidants could enhance survival time, protect liver and lung from oxidative damage and reduce accumulation of purine metabolites in blood following SM intoxication.

摘要

研究了多种抗氧化剂(维生素E的水溶性类似物托洛克斯、生物类黄酮槲皮素和还原型谷胱甘肽(GSH))在硫芥(SM)中毒后的保护作用。通过吸入(1小时内1 LC50 = 42.3毫克/立方米;观察14天的死亡率)和经皮(1 LD50 = 154.7毫克/千克;观察7天的死亡率)途径给瑞士白化雌性小鼠施用起泡剂SM。抗氧化剂通过腹腔注射,以托洛克斯500微克/千克、槲皮素5毫克/千克和GSH 400毫克/千克体重的剂量给药三次,一次在SM暴露后立即给药,然后在SM处理后每天给药一次,共2天。研究了抗氧化剂对存活率、氧化损伤标志物和嘌呤代谢产物的影响。对存活研究动物观察14天。在SM处理72小时后,研究了氧化标志物(血液、肝脏和肺中)和嘌呤代谢产物(血液和尿液中)。通过吸入途径用托洛克斯和槲皮素处理后,存活时间显著增加。GSH显著降低和丙二醛(MDA)水平升高表明,SM吸入和经皮暴露后肝脏和肺组织受到氧化损伤。嘌呤代谢终产物血液和尿液中的尿酸在两种暴露途径后均有所增加。抗氧化剂托洛克斯和槲皮素通过吸入和经皮途径保护肝脏和肺组织免受SM暴露引起的氧化损伤。这项研究表明,抗氧化剂可以延长存活时间,保护肝脏和肺免受氧化损伤,并减少SM中毒后血液中嘌呤代谢产物的积累。

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