Wickramaratna Janith C, Fry Bryan G, Hodgson Wayne C
Monash Venom Group, Department of Pharmacology, Monash University, Victoria 3800, Australia.
Toxicol Sci. 2003 Aug;74(2):352-60. doi: 10.1093/toxsci/kfg144. Epub 2003 May 28.
Based on early studies on Acanthophis antarcticus (common death adder) venom, it has long been thought that death adder snake venoms are devoid of myotoxicity. However, a recent clinical study reported rhabdomyolysis in patients following death adder envenomations, in Papua New Guinea, by a species thought to be different to A. antarcticus. Subsequently, a myotoxic phospholipase A2 component was isolated from A. rugosus (Irian Jayan death adder) venom. The present study examined the venoms of A. praelongus (northern), A. pyrrhus (desert), A. hawkei (Barkly Tableland), A. wellsi (black head), A. rugosus, A. sp. Seram and the regional variants of A. antarcticus for in vitro myotoxicity. Venoms (10-50 microg/ml) were examined for myotoxicity using the chick directly (0.1 Hz, 2 ms, supramaximal V) stimulated biventer cervicis nerve-muscle preparation. A significant contracture of skeletal muscle and/or inhibition of direct twitches were considered signs of myotoxicity. This was confirmed by histological examination. All venoms displayed high phospholipase A2 activity. The venoms (10-50 microg/ml) of A. sp. Seram, A. praelongus, A. rugosus,and A. wellsi caused a significant inhibition of direct twitches and an increase in baseline tension compared to the vehicle (n=4-6; two-way ANOVA, p<0.05). Furthermore, these venoms caused dose-dependent morphological changes in skeletal muscle. In contrast, the venoms (10-50 microg/ml; n=3-6) of A. hawkei, A. pyrrhus, and regional variants of A. antarcticus were devoid of myotoxicity. Prior incubation (10 min) of CSL death adder antivenom (5 U/ml) prevented the myotoxicity caused by A. sp. Seram, A. praelongus, A. rugosus, and A. wellsi venoms (50 microg/ml; n=4-7). In conclusion, clinicians may need to be mindful of possible myotoxicity following envenomations by A. praelongus, A. rugosus, A. sp. Seram, and A. wellsi species.
基于早期对南部棘蛇（普通死亡蝰蛇）毒液的研究，长期以来人们一直认为死亡蝰蛇的毒液没有肌毒性。然而，最近一项临床研究报告称，在巴布亚新几内亚，被认为与南部棘蛇不同的一种死亡蝰蛇致使患者出现横纹肌溶解症。随后，从棕伊澳蛇（伊里安查亚死亡蝰蛇）毒液中分离出了一种具有肌毒性的磷脂酶A2成分。本研究检测了长吻死亡蝰蛇（北部）、红死亡蝰蛇（沙漠）、霍氏死亡蝰蛇（巴克利高原）、威氏死亡蝰蛇（黑头）、棕伊澳蛇、塞拉姆岛死亡蝰蛇及南部棘蛇区域变种的毒液的体外肌毒性。使用直接刺激鸡颈二腹肌神经 - 肌肉标本（0.1赫兹，2毫秒，超强电压）检测毒液（10 - 50微克/毫升）的肌毒性。骨骼肌明显挛缩和/或直接抽搐受到抑制被视为肌毒性的迹象。组织学检查证实了这一点。所有毒液都表现出高磷脂酶A2活性。与赋形剂相比，塞拉姆岛死亡蝰蛇、长吻死亡蝰蛇、棕伊澳蛇和威氏死亡蝰蛇的毒液（10 - 50微克/毫升）致使直接抽搐明显受到抑制且基线张力增加（n = 4 - 6；双向方差分析，p < 0.05）。此外，这些毒液在骨骼肌中引起剂量依赖性形态变化。相比之下，霍氏死亡蝰蛇、红死亡蝰蛇及南部棘蛇区域变种的毒液（10 - 50微克/毫升；n = 3 - 6）没有肌毒性。用CSL死亡蝰蛇抗蛇毒血清（5单位/毫升）预先孵育（10分钟）可预防塞拉姆岛死亡蝰蛇、长吻死亡蝰蛇、棕伊澳蛇和威氏死亡蝰蛇毒液（50微克/毫升；n = 4 - 7）所造成的肌毒性。总之，临床医生可能需要留意长吻死亡蝰蛇、棕伊澳蛇、塞拉姆岛死亡蝰蛇和威氏死亡蝰蛇物种致伤后可能出现的肌毒性。
