Bosentan, a selective and more potent antagonist for Atractaspis envenomation than the specific antivenom
Bosentan, a selective and more potent antagonist for Atractaspis envenomation than the specific antivenom
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DOI：
10.1016/j.toxicon.2011.03.002
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发表时间：
2011-05-01
期刊：
影响因子：
2.8
通讯作者：
Abd-Elsalam, M. A.
中科院分区：
文献类型：
--
作者：
Abd-Elsalam, M. A.
2007年在利雅得的NAVPC首次制备了抗棘球绦虫的抗蛇毒血清，但这是一个漫长而昂贵的过程。在本研究中，使用以下方法测试替代治疗：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，因为蛇毒毒性组分在结构和作用上相似（Sarafotoxins）和内皮素和3-与硝酸甘油和波生坦相比的特异性抗蛇毒血清。抗蛇毒血清或波生坦完全保护所有兔子免受最小致死剂量的毒液或其毒性部分的伤害。另一方面，在注射一个最小致死剂量（MLD）的毒液或毒性组分后几分钟（min）和在死亡前出现缺血的第一个迹象时注射三种药物中的任何一种，表明波生坦完全挽救了所有家兔。在硝酸甘油的情况下，所有兔子都死亡，而在抗蛇毒血清的情况下，10只兔子中只有5只获救。很明显，波生坦在保护家兔方面上级特异性抗蛇毒血清;这可能是由于其对内皮素受体的亲和力高于sarafotoxins。这项临床前研究显示，波生坦作为选择性解毒剂治疗非洲盾介壳虫毒液蛰入具有良好的潜力，尤其是在非洲大陆。(C)2011爱思唯尔有限公司版权所有。
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. (C) 2011 Elsevier Ltd. All rights reserved.