Species and Regional Variations in the Effectiveness of Antivenom against the in Vitro Neurotoxicity of Death Adder (Acanthophis) Venoms

• Published in: Toxicology and applied pharmacology 2001-09, Vol.175 (2), p.140-148
• Main Authors: Fry, Bryan G., Wickramaratna, Janith C., Jones, Alun, Alewood, Paul F., Hodgson, Wayne C.
• Format: Article
• Language: English
• Subjects: Acanthophis; Analysis of Variance; Animal poisons toxicology. Antivenoms; Animals; Antivenins - therapeutic use; antivenom; Biological and medical sciences; Chickens; Chromatography, Liquid; death adder; Elapid Venoms - analysis; Elapid Venoms - antagonists & inhibitors; Elapid Venoms - toxicity; Electric Stimulation; Male; Medical sciences; Neuromuscular Junction - drug effects; neurotoxic; postsynaptic; Species Specificity; Toxicology; venom
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.2001.9233

Although viperlike in appearance and habit, death adders belong to the Elapidae family of snakes. Systemic envenomation represents a serious medical problem with antivenom, which is raised against Acanthophis antarcticus venom, representing the primary treatment. This study focused on the major Acanthophis variants from Australia and islands in the Indo-Pacific region. Venoms were profiled using liquid chromatography–mass spectrometry, and analyzed for in vitro neurotoxicity (0.3–10 μg/ml), as well as the effectiveness of antivenom (1–5 units/ml; 10 min prior to the addition of 10 μg/ml venom). The following death adder venoms were examined: A. antarcticus (from separate populations in New South Wales, Queensland, South Australia, and Western Australia), A. hawkei, A. praelongus, A. pyrrhus, A. rugosus, A. wellsi, and venom from an unnamed species from the Indonesian island of Seram. All venoms abolished indirect twitches of the chick isolated biventer cervicis nerve-muscle preparation in a dose-dependent manner. In addition, all venoms blocked responses to exogenous acetylcholine (1 mM) and carbachol (20 μM), but not KCl (40 mM), suggesting postsynaptic neurotoxicity. Death adder antivenom (1 unit/ml) prevented the neurotoxic effects of A. pyrrhus, A. praelongus, and A. hawkei venoms, although it was markedly less effective against venoms from A. antarcticus (NSW, SA, WA), A. rugosus, A. wellsi, and A. sp. Seram. However, at 5 units/ml, antivenom was effective against all venoms tested. Death adder venoms, including those from A. antarcticus geographic variants, differed not only in their venom composition but also in their neurotoxic activity and susceptibility to antivenom. For the first time toxicological aspects of A. hawkei, A. wellsi, A. rugosus, and A. sp. Seram venoms were studied.