Respiratory compromise in Crotalus durissus terrificus (C.d.t.) snakebite is an important pathological condition. Considering that crotoxin (CTX), a phospholipase A2 from C.d.t. venom, is the main component of the venom, the present work investigated the toxin effects on respiratory failure. Lung mechanics, morphology and soluble markers were evaluated from Swiss male mice, and mechanism determined using drugs/inhibitors of eicosanoids biosynthesis pathway and autonomic nervous system. Acute respiratory failure was observed, with an early phase (within 2 h) characterized by enhanced presence of eicosanoids, including prostaglandin E2, that accounted for the increased vascular permeability in the lung. The alterations of early phase were inhibited by indomethacin. The late phase (peaked 12 h) was marked by neutrophil infiltration, presence of pro-inflammatory cytokines/chemokines, and morphological alterations characterized by alveolar septal thickening and bronchoconstriction. In addition, lung mechanical function was impaired, with decreased lung compliance and inspiratory capacity. Hexamethonium, a nicotinic acetylcholine receptor antagonist, hampered late phase damages indicating that CTX-induced lung impairment could be associated with cholinergic transmission. The findings reported herein highlight the impact of CTX on respiratory compromise, and introduce the use of nicotinic blockers and prostanoids biosynthesis inhibitors as possible symptomatic therapy to Crotalus durissus terrificus snakebite.

中文翻译：

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Crotoxin诱导的小鼠肺功能损害：烟碱乙酰胆碱受体和COX衍生的前列腺素的作用。

响尾蛇（Crotalus durissus terrificus，Cdt）蛇咬伤的呼吸损害是一种重要的病理状况。考虑到回毒素（CTX）是Cdt毒液中的磷脂酶A2，是毒液的主要成分，本研究调查了该毒素对呼吸衰竭的影响。从瑞士雄性小鼠中评估肺力学，形态学和可溶性标志物，并使用类花生酸生物合成途径和自主神经系统的药物/抑制剂确定其机制。观察到急性呼吸衰竭，早期（2小时内）的特征是类花生酸（包括前列腺素E2）的存在增加，这说明肺血管渗透性增加。消炎痛抑制了早期的变化。晚期（高峰12小时）以中性粒细胞浸润为特征，促炎细胞因子/趋化因子的存在，以及以肺泡间隔增厚和支气管收缩为特征的形态改变。此外，肺机械功能受损，肺顺应性和吸气能力下降。烟酸乙酰胆碱受体拮抗剂六甲铵（Hexamethonium）阻碍了晚期损伤，表明CTX诱导的肺功能障碍可能与胆碱能传递有关。本文报道的发现凸显了CTX对呼吸系统损害的影响，并介绍了烟碱类阻断剂和类前列腺素生物合成抑制剂的使用，作为对Crotarus durissus terrificus snakebite的可能对症治疗。肺机械功能受损，肺顺应性和吸气能力下降。烟酸乙酰胆碱受体拮抗剂六甲铵（Hexamethonium）阻碍了晚期损伤，表明CTX诱导的肺功能障碍可能与胆碱能传递有关。本文报道的发现凸显了CTX对呼吸系统损害的影响，并介绍了烟碱类阻断剂和类前列腺素生物合成抑制剂的使用，作为对Crotarus durissus terrificus snakebite的可能对症治疗。肺机械功能受损，肺顺应性和吸气能力下降。烟酸乙酰胆碱受体拮抗剂六甲铵（Hexamethonium）阻碍了晚期损伤，表明CTX诱导的肺功能障碍可能与胆碱能传递有关。本文报道的发现凸显了CTX对呼吸系统损害的影响，并介绍了烟碱类阻断剂和类前列腺素生物合成抑制剂的使用，作为对Crotarus durissus terrificus snakebite的可能对症治疗。