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波生坦是一种选择性的、比特定抗蛇毒血清更有效的抗阿特拉特西斯蛇毒的拮抗剂。

Bosentan, a selective and more potent antagonist for Atractaspis envenomation than the specific antivenom.

机构信息

The National Antivenom and Vaccine Production Center (NAVPC), Riyadh, Saudi Arabia.

出版信息

Toxicon. 2011 May;57(6):861-70. doi: 10.1016/j.toxicon.2011.03.002. Epub 2011 Mar 15.

DOI:10.1016/j.toxicon.2011.03.002
PMID:21392521
Abstract

Preparation of an antivenom against Atractaspis had been done for the first time in the year 2007 in NAVPC in Riyadh, however, it was a lengthy and expensive process. In this study, an alternative treatment was tested using: 1- Nitroglycerin to antagonize the coronary vasospasm induced by the venom, 2- Bosentan to block the endothelin receptors since there is a similarity in structure and effect between the toxic fraction of venom (Sarafotoxins) and endothelins and 3- The specific Antivenom in comparison to nitroglycerin and bosentan. Pretreatment of rabbits with nitroglycerin, antivenom or bosentan completely protected all rabbits from the minimal lethal doses of venom or its toxic fraction. On the other hand, injecting any of the three drugs a few minutes (min) after injecting one minimal lethal dose (MLD) of the venom or the toxic fraction and at the first signs of ischemia, just before death, showed that bosentan completely saved all rabbits. In case of nitroglycerin all rabbits died and in case of antivenom, only 5 out of 10 rabbits were rescued. It is clear that bosentan is superior to the specific antivenom in protecting rabbits; this may be due to its higher affinity to endothelin receptors than sarafotoxins. This preclinical study shows a good potential in using bosentan as a selective antidote for atractaspis envenomation, especially in the African continent.

摘要

2007 年,NAVPC 在利雅得首次制备了抗 Atractaspis 抗蛇毒血清,但这是一个漫长而昂贵的过程。在这项研究中,使用以下方法测试了替代治疗方法:1- 硝酸甘油拮抗蛇毒引起的冠状动脉痉挛,2- 波生坦阻断内皮素受体,因为毒液的有毒部分(Sarafotoxins)和内皮素在结构和作用上有相似性,3- 与硝酸甘油和波生坦相比,特异性抗蛇毒血清。用硝酸甘油、抗蛇毒血清或波生坦预处理兔子可完全保护所有兔子免受最小致死剂量的毒液或其有毒部分的影响。另一方面,在注射最小致死剂量(MLD)毒液或其有毒部分几分钟(min)后,或在出现缺血的第一个迹象之前,即死亡前,注射这三种药物中的任何一种,波生坦可完全挽救所有兔子。硝酸甘油组的所有兔子均死亡,抗蛇毒血清组只有 10 只兔子中的 5 只获救。很明显,波生坦在保护兔子方面优于特异性抗蛇毒血清,这可能是由于其与内皮素受体的亲和力高于 Sarafotoxins。这项临床前研究表明,波生坦作为 Atractaspis 蛇毒中毒的选择性解毒剂具有良好的潜力,特别是在非洲大陆。

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