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新型解毒剂牛黄可预防蟾蜍(中华大蟾蜍)毒液对小鼠的心脏毒性。

The novel antidote Bezoar Bovis prevents the cardiotoxicity of Toad (Bufo bufo gargarizans Canto) Venom in mice.

作者信息

Ma Hongyue, Zhou Jing, Jiang Jiejun, Duan Jinao, Xu Huiqin, Tang Yuping, Lv Gaohong, Zhang Junfeng, Zhan Zhen, Ding Anwei

机构信息

Jiangsu Key Laboratory for TCM Formulae Research, Nanjing University of Chinese Medicine, Nanjing 210046, PR China.

出版信息

Exp Toxicol Pathol. 2012 Jul;64(5):417-23. doi: 10.1016/j.etp.2010.10.007. Epub 2010 Nov 16.

DOI:10.1016/j.etp.2010.10.007
PMID:21084181
Abstract

Toad Venom, called chansu (CS) in China, is an anti-inflammatory drug used in small doses for the treatment of various types of inflammation in China. Its use is hampered by the cardiotoxicity of bufadienolides derived from Toad Venom. Bezoar Bovis is another frequently used drug in Toad Venom preparations for the treatment of inflammatory or cardiovascular diseases in Asia. We explored whether Bezoar Bovis could protect against CS-induced acute toxicity in mice. Toxicity was assessed by the general features of poisoning, electrocardiography (ECG), and levels of creatine kinase (CK), lactate dehydrogenase (LDH) and calcium ions (Ca(2+)) in cardiac tissues. Toad Venom (90 mg/kg) caused opisthotonus, ventricular arrhythmias, and increases in cardiac levels of Ca(2+), CK and LDH. Pretreatment with Bezoar Bovis (120, 240 and 480 mg/kg) significantly reduced the prevalence of opisthotonus and mortality, and prevented cardiotoxicity in CS-treated mice as evidenced by decreases in the scores of arrhythmias and cardiac levels of CK, LDH and Ca(2+). Furthermore, the bilirubin, and taurine derived from Bezoar Bovis offered marked protection against the arrhythmias induced by CS or bufalin in vivo and in vitro. An anti-inflammatory study showed that Bezoar Bovis did not compromise the anti-inflammatory activity of Toad Venom on concanavalin-A (ConA)-stimulated proliferation of human peripheral blood mononuclear cells. These results suggested that Bezoar Bovis elicited protective and anti-arrhythmic effects against Toad Venom intoxication in mice, and is a novel antidote in combination with Toad Venom therapy.

摘要

蟾酥在中国被称为“蟾酥”(CS),是一种抗炎药物,在中国小剂量用于治疗各种炎症。其应用受到蟾酥中蟾毒配基心脏毒性的限制。牛黄是亚洲常用于蟾酥制剂治疗炎症或心血管疾病的另一种药物。我们探讨了牛黄是否能预防CS诱导的小鼠急性毒性。通过中毒的一般特征、心电图(ECG)以及心脏组织中肌酸激酶(CK)、乳酸脱氢酶(LDH)和钙离子(Ca(2+))水平来评估毒性。蟾酥(90 mg/kg)可引起角弓反张、室性心律失常,并使心脏组织中Ca(2+)、CK和LDH水平升高。用牛黄(120、240和480 mg/kg)预处理可显著降低角弓反张的发生率和死亡率,并预防CS处理小鼠的心脏毒性,心律失常评分以及心脏组织中CK、LDH和Ca(2+)水平降低证明了这一点。此外,牛黄衍生的胆红素和牛磺酸在体内和体外对CS或蟾毒灵诱导的心律失常均有显著保护作用。一项抗炎研究表明,牛黄不会损害蟾酥对刀豆蛋白A(ConA)刺激的人外周血单个核细胞增殖的抗炎活性。这些结果表明,牛黄对小鼠蟾酥中毒具有保护和抗心律失常作用,是与蟾酥联合治疗的一种新型解毒剂。

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