Species-Dependent Variations in the in Vitro Myotoxicity of Death Adder (Acanthophis) Venoms

• Published in: Toxicological Sciences
• Main Authors: Wickramaratna, Janith C., Fry, Bryan G., Hodgson, Wayne C.
• Format: Text
• Language: English
• Published: Oxford University Press 2003
• Subjects: IN VITRO TOXICOLOGY AND ALTERNATIVE TESTING; Antarc*; antarcticus
• Online Access: http://toxsci.oxfordjournals.org/cgi/content/short/74/2/352; https://doi.org/10.1093/toxsci/kfg144

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 A 2 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 μg/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 A 2 activity. The venoms (10–50 μg/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 μg/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 μg/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.