Valério Souza Natália Muradas, Ramos Pinto Êmylle Karoline, Maciel Fernanda Valadares, de Abreu Thales Augusto Gonçalves, Ortolani Paula Ladeira, Fortes-Dias Consuelo Latorre, Cavalcante Walter Luís Garrido
Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Avenida Antônio Carlos 6627 - Pampulha, Belo Horizonte, MG, 31270-901, Brazil.
Diretoria de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias (FUNED), Rua Conde Pereira Carneiro, 80 - Gameleira, Belo Horizonte, MG, 30510-010, Brazil.
Toxicon. 2025 Jul 8;265:108490. doi: 10.1016/j.toxicon.2025.108490.
Crotalus durissus terrificus, commonly known as the South American rattlesnake, is a snake of medical relevance in Brazil. Its wide geographical distribution correlates with biochemical variations in venom composition, which can affect the typical pharmacological effects, such as neurotoxicity and myotoxicity. These effects are primarily attributed to crotoxin, the major toxic component of the venom, comprising over 50 % of its dry mass. Considering the lethality of crotali venoms from Brazil, the comparative study of their biological activities can provide subsidies for the development of a more effective antiophidic therapy, as well as guide and expand biochemical and pharmacological studies.
We compared the toxic effects of crude Crotalus durissus terrificus venoms (1, 5, and 10 μg/mL) and their crotoxins (1 and 5 μg/mL) on mice neuromuscular preparations, through a myographic study, using venoms from four different municipalities (Carrancas, Patos de Minas, Nova Ponte and Nazareno) of Minas Gerais state, Brazil. Histological analyses were also performed to evaluate the toxic effects of these substances on the mice muscle tissues.
Both venoms and crotoxins induced a time- and concentration-dependent blockade over a period of 180 min. At 1 μg/mL, significant differences were observed between the venoms from Carrancas and Nazareno. Furthermore, all crotoxins displayed distinct blockade kinetics at this concentration, highlighting regional variations in composition and pharmacological activities of the venoms and toxins. Additionally, all venoms induced muscle damage at 5 and 10 μg/mL, while only CTXs from Carrancas and Nazareno caused detectable damage.
Our findings emphasize the importance of understanding the natural history and venom composition of snake populations, particularly for widely distributed species. Intraspecific venom variability may result in different clinical manifestations, which may be considered in the therapeutics of Crotalus durissus envenomation.
南美响尾蛇（Crotalus durissus terrificus），通常被称为南美蝰蛇，是巴西一种具有医学相关性的蛇类。其广泛的地理分布与毒液成分的生化变异相关，这可能会影响典型的药理作用，如神经毒性和肌毒性。这些作用主要归因于响尾蛇毒素，它是毒液的主要毒性成分，占其干重的50%以上。考虑到巴西响尾蛇毒液的致死性，对其生物活性进行比较研究可为开发更有效的抗蛇毒疗法提供支持，并指导和拓展生化及药理研究。
我们通过肌电图研究，比较了来自巴西米纳斯吉拉斯州四个不同城市（卡兰卡、帕托斯迪米纳斯、新蓬蒂和拿撒勒）的南美响尾蛇粗毒（1、5和10μg/mL）及其响尾蛇毒素（1和5μg/mL）对小鼠神经肌肉制剂的毒性作用。还进行了组织学分析，以评估这些物质对小鼠肌肉组织的毒性作用。
毒液和响尾蛇毒素在180分钟内均诱导了时间和浓度依赖性的阻滞。在1μg/mL时，观察到卡兰卡和拿撒勒的毒液之间存在显著差异。此外，所有响尾蛇毒素在此浓度下均表现出不同的阻滞动力学，突出了毒液和毒素在成分和药理活性方面的区域差异。此外，所有毒液在5和10μg/mL时均诱导肌肉损伤，但只有来自卡兰卡和拿撒勒的响尾蛇毒素导致了可检测到的损伤。
我们的研究结果强调了了解蛇类种群自然史和毒液成分的重要性，特别是对于分布广泛的物种。种内毒液变异性可能导致不同的临床表现，这在南美响尾蛇咬伤的治疗中可能需要考虑。
