Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, 13083-887, Campinas, SP, Brazil.
Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, 13083-887, Campinas, SP, Brazil.
Toxicology. 2014 Sep 2;323:109-24. doi: 10.1016/j.tox.2014.06.010. Epub 2014 Jun 25.
Envenoming by the pitviper Bothrops jararacussu produces cardiovascular alterations, including coagulopathy, systemic hemorrhage, hypotension, circulatory shock and renal failure. In this work, we examined the activity of this venom in rat isolated right atria. Incubation with venom (0.025, 0.05, 0.1 and 0.2mg/ml) caused concentration-dependent muscle contracture that was not reversed by washing. Muscle damage was seen histologically and confirmed by quantification of creatine kinase-MB (CK-MB) release. Heating and preincubation of venom with p-bromophenacyl bromide (a phospholipase A2 inhibitor) abolished the venom-induced contracture and muscle damage. In contrast, indomethacin, a non-selective inhibitor of cyclooxygenase, and verapamil, a voltage-gated Ca(2+) channel blocker, did not affect the responses to venom. Preincubation of venom with Bothrops or Bothrops/Crotalus antivenom or the addition of antivenom soon after venom attenuated the venom-induced changes in atrial function and tissue damage. These results indicate that B. jararacussu venom adversely affected rat atrial contractile activity and muscle organization through the action of venom PLA2; these venom-induced alterations were attenuated by antivenom.
矛头蝮蛇(Bothrops jararacussu)的毒液会导致心血管改变,包括凝血功能障碍、全身性出血、低血压、循环休克和肾衰竭。在这项工作中,我们研究了这种毒液对大鼠离体右心房的作用。孵育毒液(0.025、0.05、0.1 和 0.2mg/ml)会引起浓度依赖性的肌肉收缩,且通过清洗无法逆转。组织学观察到肌肉损伤,并通过肌酸激酶同工酶-MB(CK-MB)释放的定量来证实。加热和用对溴苯甲酰溴(一种磷脂酶 A2 抑制剂)预孵育毒液可消除毒液引起的收缩和肌肉损伤。相比之下,非选择性环氧化酶抑制剂吲哚美辛和电压门控 Ca(2+)通道阻滞剂维拉帕米对毒液的反应没有影响。毒液与 Bothrops 或 Bothrops/Crotalus 抗蛇毒血清预孵育或在毒液后立即加入抗蛇毒血清可减轻毒液对心房功能和组织损伤的影响。这些结果表明,矛头蝮蛇的毒液通过其 PLA2 作用对大鼠心房收缩活动和肌肉组织产生不利影响;这些毒液引起的改变可被抗蛇毒血清减轻。