Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal Do Ceará, Fortaleza, Ceará, Brazil; Facultad de Ciencias Naturales, Exactas y de la Educación, Departamento de Biología, Centro de Investigaciones Biomédicas-Bioterio, Grupo de Investigaciones Herpetológicas y Toxinológicas, Universidad del Cauca, Popayán, Colombia.
Facultad de Ciencias Naturales, Exactas y de la Educación, Departamento de Biología, Centro de Investigaciones Biomédicas-Bioterio, Grupo de Investigaciones Herpetológicas y Toxinológicas, Universidad del Cauca, Popayán, Colombia.
Toxicon. 2020 Sep;184:180-191. doi: 10.1016/j.toxicon.2020.06.009. Epub 2020 Jun 23.
In Colombia, Lachesis acrochorda causes 2-3% of all snake envenomations. The accidents promote a high mortality rate (90%) due to blood and cardiovascular complications. Here, the effects of the snake venom of L. acrochorda (SVLa) were analyzed on human blood cells and on cardiovascular parameters of rats. SVLa induced blood coagulation, as measured by the prothrombin time test, but did not reduce the cell viability of neutrophils and platelets evaluated by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay and by the lactate dehydrogenase (LDH) enzyme assay. In fact, SVLa increased the absorbance in tests made with platelets subjected to the MTT assay. SVLa induced platelet aggregation whose magnitude was comparable to that of the positive control adenosine diphosphate (ADP), and occurred earlier with increasing SVLa concentration. Acetylsalicylic acid (ASA, a cyclooxygenase inhibitor) or clopidogrel (an ADP receptor blocker) inhibited the aggregating effect of SVLa. Inhibition of SVLa-elicited platelet aggregation also resulted from the treatment with disodium ethylenediaminetetraacetate (Na-EDTA; metalloproteinase inhibitor) and with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF, serine protease inhibitor). In isolated right atrium of rats, SVLa increased slightly, but significantly, the magnitude of the spontaneous contractions and, in isolated rat aorta, SVLa relaxed KCl- or phenylephrine-induced contractions. In vivo, SVLa induced hypotension and bradycardia in rats, with detection of hemorrhage in pulmonary and renal tissues. Altogether, under experimental conditions, SVLa induced blood coagulation, platelet aggregation, hypotension and bradycardia. Part of the effects presented here may be explained by the presence of snake venom metalloproteinases (SVMPs) and snake venom serine proteases (SVSPs), constituents of SVLa.
在哥伦比亚，矛头蝮属的矛头蛇（Lachesis acrochorda）导致了所有蛇咬伤的 2-3%。这些事故导致了高死亡率（90%），原因是血液和心血管并发症。在这里，分析了矛头蛇蛇毒（SVLa）对人血细胞和大鼠心血管参数的影响。SVLa 通过凝血酶原时间试验诱导血液凝固，但通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴化物（MTT）还原试验和乳酸脱氢酶（LDH）酶试验评估，不会降低中性粒细胞和血小板的细胞活力。事实上，SVLa 增加了在 MTT 试验中用血小板进行的测试的吸光度。SVLa 诱导血小板聚集，其幅度与阳性对照二磷酸腺苷（ADP）相当，并且随着 SVLa 浓度的增加而更早发生。乙酰水杨酸（ASA，环氧化酶抑制剂）或氯吡格雷（ADP 受体阻滞剂）抑制 SVLa 的聚集作用。SVLa 诱导的血小板聚集的抑制也来自于乙二胺四乙酸二钠（Na-EDTA；金属蛋白酶抑制剂）和 4-(2-氨基乙基)苯磺酰氟盐酸盐（AEBSF，丝氨酸蛋白酶抑制剂）的处理。在大鼠右心房分离中，SVLa 略微但显著地增加了自发收缩的幅度，并且在大鼠主动脉分离中，SVLa 使 KCl 或苯肾上腺素诱导的收缩松弛。在体内，SVLa 导致大鼠低血压和心动过缓，并在肺和肾组织中检测到出血。总之，在实验条件下，SVLa 诱导血液凝固、血小板聚集、低血压和心动过缓。这里呈现的部分影响可能可以通过 SVLa 中存在的蛇毒金属蛋白酶（SVMPs）和蛇毒丝氨酸蛋白酶（SVSPs）来解释，它们是 SVLa 的组成部分。
