Torres-Bonilla Kristian A, Schezaro-Ramos Raphael, Floriano Rafael Stuani, Rodrigues-Simioni Léa, Bernal-Bautista Manuel H, Alice da Cruz-Höfling Maria
Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Cidade Universitária Zeferino Vaz, 13083-862, Campinas, SP, Brazil; Department of Biology, Universidad del Tolima, Barrio Santa Helena Parte Alta, 731020, Ibagué, Tolima, Colombia.
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, 13083-887, Campinas, SP, Brazil.
Toxicon. 2016 Sep 1;119:345-51. doi: 10.1016/j.toxicon.2016.07.004. Epub 2016 Jul 4.
The physiological properties of colubrid snake venoms are largely unknown and less frequently investigated. In this study, we assessed the enzymatic properties and biological activities of Leptodeira annulata (banded cat-eyed snake) venom, an opistoglyphous snake from Colombia. The proteolytic, phospholipase A2 and amidolytic activities are assessed using colorimetric assays and the biological activities were analyzed in avian and mammalian neuromuscular preparations. L. annulata venom caused neuromuscular blockade in chick biventer cervicis (BC) preparations (40± 15% and 50± 3% of twitch reduction for 30 and 100 μg/ml, respectively; p < 0.05) following 120 incubation; 10 μg/ml of venom did not induce blockade. There was a mild reduction in contracture response to exogenous acetylcholine (110 μM) in BC preparations exposed to 10 and 30 μg of venom/ml (∼4% and ∼32% of reduction, respectively, p > 0.05, n = 4) compared to basal values whereas the highest concentration (100 μg/ml) abolished it after 120 min. The venom caused a significant reduction in contracture response elicited by KCl (∼58 and ∼90 of reduction for 30 and 100 μg/ml, respectively, p < 0.05, n = 4). In mouse phrenic nerve-diaphragm (PND) preparations, L. annulata venom induced a progressive muscle membrane depolarization [from -85.9 ± 1.6 mV (t0) to -72.2 ± 2.9 mV (t120), p < 0.05, n = 4); the postsynaptic receptors remained functional as shown by carbachol-induced depolarization. The morphological analyses showed a concentration-dependent number of pathological states in muscle fibers from both BC and PND preparations pre-exposed to venom. The venom showed high proteolytic activity and low phospholipase A2 activity; there was no evidence for serine protease activity. These results indicate that the neuromuscular effect induced by L. annulata venom resulted from damaged muscle fibers that lead to the blockade of twitches response. The findings suggest that the myotoxicity might be related to the presence of metalloproteases in this venom.
黄颌蛇科蛇毒的生理特性在很大程度上尚不明确,且较少受到研究。在本研究中,我们评估了来自哥伦比亚的后沟牙毒蛇——环纹斜鳞蛇(Leptodeira annulata,带纹猫眼蛇)毒液的酶活性和生物活性。使用比色法评估其蛋白水解、磷脂酶A2和酰胺水解活性,并在禽类和哺乳动物神经肌肉制剂中分析其生物活性。环纹斜鳞蛇毒液在孵育120分钟后,导致鸡颈二腹肌(BC)制剂出现神经肌肉阻滞(30和100μg/ml时抽搐减少分别为40±15%和50±3%;p<0.05);10μg/ml的毒液未诱导阻滞。与基础值相比,暴露于10和30μg/ml毒液的BC制剂对外源性乙酰胆碱(110μM)的挛缩反应略有降低(分别约降低4%和约32%,p>0.05,n = 4),而最高浓度(100μg/ml)在120分钟后使其消失。该毒液使氯化钾引起的挛缩反应显著降低(30和100μg/ml时分别约降低58%和90%,p<0.05,n = 4)。在小鼠膈神经-膈肌(PND)制剂中,环纹斜鳞蛇毒液诱导肌肉膜逐渐去极化[从-85.9±1.6mV(t0)到-72.2±2.9mV(t120),p<0.05,n = 4];如卡巴胆碱诱导的去极化所示,突触后受体仍保持功能。形态学分析显示,预先暴露于毒液的BC和PND制剂的肌纤维中,病理状态的数量呈浓度依赖性。该毒液显示出高蛋白水解活性和低磷脂酶A2活性;没有丝氨酸蛋白酶活性的证据。这些结果表明,环纹斜鳞蛇毒液诱导的神经肌肉效应是由受损的肌纤维导致抽搐反应阻滞引起的。研究结果表明,这种毒液的肌毒性可能与金属蛋白酶的存在有关。