Species and regional variations in the effectiveness of antivenom against the in vitro neurotoxicity of death adder (Acanthophis) venoms.
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 microg/ml), as well as the effectiveness of antivenom (1-5 units/ml; 10 min prior to the addition of 10 microg/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 microM), 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.
Fry
B G
BG
The Centre for Drug Design and Development, University of Queensland, St. Lucia, Queensland, 4072, Australia.
Wickramaratna
J C
JC
Jones
A
A
Alewood
P F
PF
Hodgson
W C
WC
D000704:Analysis of Variance; D000818:Animals; D000997:Antivenins / Q000627:therapeutic use*; D002645:Chickens; D002853:Chromatography, Liquid; D004546:Elapid Venoms / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004558:Electric Stimulation; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects*; D013045:Species Specificity
D000997:Antivenins; D004546:Elapid Venoms