Protective effects of Y-27632 on acute dichlorvos poisoning in rats
Protective effects of Y-27632 on acute dichlorvos poisoning in rats
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DOI：
10.1016/j.ajem.2008.11.020
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发表时间：
2010-03-01
影响因子：
3.6
通讯作者：
Demiryurek, Abdullah T.
中科院分区：
文献类型：
--
作者：
Gunay, Nurullah;Kose, Beril;Demiryurek, Abdullah T.
抗胆碱酯酶中毒是发展中国家的一个重要健康问题，了解其潜在机制是有效治疗的关键。本研究旨在观察选择性Rho-Kinase抑制剂Y-27632对有机磷诱导的大鼠心脏毒性和死亡率的影响。将大鼠随机分为4组：对照组(玉米油)、敌敌畏(30 mg/kg)组、Y-27632+敌敌畏1、10 mg/kg组。腹腔注射6h后，取静脉血和心脏标本，进行生化或免疫组织化学分析，记录肌颤强度。敌敌畏可抑制血清胆碱酯酶活性，Y-27632可抑制这种活性。中毒或Y-27632对血清肌酸激酶、肌酸激酶-MB活性、肌红蛋白和N末端前脑利钠肽浓度没有明显影响。虽然血清一氧化氮浓度不随敌敌畏的变化而变化，但经Y-27632预先处理后，心脏一氧化氮水平显著升高。添加1 mg/kg Y-27632的小鼠心脏谷胱甘肽水平也升高。没有细胞凋亡的染色，诱导型一氧化氮合酶的免疫组织化学分析显示所有组的心脏组织没有变化。两种剂量的Y-27632均可降低急性敌敌畏暴露大鼠的死亡率(100%存活率)。这些结果表明，给予Rho-Kinase抑制剂可对敌敌畏中毒大鼠产生保护作用。这些发现可能为有机磷中毒的治疗提供新的可能性。(C)2010 Elsevier Inc.保留所有权利。
Anticholinesterase poisoning is an important health problem in developing countries, and understanding of its underlying mechanisms is essential for the effective treatment. This study is designed to examine the effects of Y-27632, a selective Rho-kinase inhibitor, on organophosphate-induced cardiac toxicity and mortality in rats. Rats were randomly divided into 4 groups: control (corn oil), dichlorvos (30 mg/kg intraperitoneally), and 1- and 10-mg/kg Y-27632 + dichlorvos groups. After 6 hours of intraperitoneal injection, venous blood and cardiac samples were obtained, biochemical or immunohistochemical analyses were performed, and the intensity of muscle fasciculation was recorded. Serum cholinesterase activities were suppressed with dichlorvos, and these reductions were inhibited with Y-27632 pretreatment. Serum creatine kinase, creatine kinase-MB activities, and myoglobin and N-terminal probrain natriuretic peptide concentrations were not markedly affected with poisoning or Y-27632. Although serum nitric oxide concentrations did not change with dichlorvos, cardiac nitric oxide levels were markedly increased with Y-27632 pretreatment. Cardiac glutathione levels also increased with 1 mg/kg Y-27632. There was no staining for apoptosis, and immunohistochemical analyses of inducible nitric oxide synthase showed no change in cardiac tissue for all of the groups. Both doses of Y-27632 abolished mortality in rats with acute dichlorvos exposure (100% survival). These results show that administration of Rho-kinase inhibitor can produce protective effects against dichlorvos intoxication in rats. These findings may provide new possibilities for the treatment of organophosphate poisoning. (C) 2010 Elsevier Inc. All rights reserved.