Abstract
Bungarus multicinctus, the Chinese krait, is a highly venomous elapid snake which causes considerable morbidity and mortality in southern China. B. multicinctus venom contains pre-synaptic PLA2 neurotoxins (i.e., β-bungarotoxins) and post-synaptic neurotoxins (i.e., α-bungarotoxins). We examined the in vitro neurotoxicity of B. multicinctus venom, and the efficacy of specific monovalent Chinese B. multicinctus antivenom, and Australian polyvalent elapid snake antivenom, against venom-induced neurotoxicity. B. multicinctus venom (1–10 μg/mL) abolished indirect twitches in the chick biventer cervicis nerve-muscle preparation as well as attenuating contractile responses to exogenous ACh and CCh, but not KCl. This indicates a post-synaptic neurotoxic action but myotoxicity was not evident. Given that post-synaptic α-neurotoxins have a more rapid onset than pre-synaptic neurotoxins, the activity of the latter in the whole venom will be masked. The prior addition of Chinese B. multicinctus antivenom (12 U/mL) or Australian polyvalent snake antivenom (15 U/mL), markedly attenuated the neurotoxic actions of B. multicinctus venom (3 μg/mL) and prevented the inhibition of contractile responses to ACh and CCh. The addition of B. multicinctus antivenom (60 U/mL), or Australian polyvalent snake antivenom (50 U/mL), at the t90 time point after the addition of B. multicinctus venom (3 μg/mL), did not restore the twitch height over 180 min. The earlier addition of B. multicinctus antivenom (60 U/mL), at the t20 or t50 time points, also failed to prevent the neurotoxic effects of the venom but did delay the time to abolish twitches based on a comparison of t90 values. Repeated washing of the preparation with physiological salt solution, commencing at the t20 time point, failed to reverse the neurotoxic effects of venom or delay the time to abolish twitches. This study showed that B. multicinctus venom displays marked in vitro neurotoxicity in a skeletal muscle preparation which is not reversed by antivenom. This does not appear to be related to antivenom efficacy, but due to the irreversible/pseudo-irreversible nature of the neurotoxins.
Highlights
Bungarus genus are nocturnal venomous snakes from the Elapidae family that are only found in Asia with widespread distribution across many countries includingIndia, Pakistan, Indonesia, Sri Lanka, Malaysia, Bangladesh, Vietnam and China
Robust epidemiological data is lacking, it has been estimated that B. multicinctus bites account for approximately 8% of all snakebites in China, while B. fasciatus bites account for 2.3% [2]
B. multicinctus venom (1–10 μg/mL) caused concentration-dependent inhibition of indirect twitches in the chick biventer preparation when compared to vehicle (n = 6; one-way analysis of variance (ANOVA), p < 0.05; Figure 1a)
Summary
Bungarus genus (kraits) are nocturnal venomous snakes from the Elapidae family that are only found in Asia with widespread distribution across many countries includingIndia, Pakistan, Indonesia, Sri Lanka, Malaysia, Bangladesh, Vietnam and China. Bungarus genus (kraits) are nocturnal venomous snakes from the Elapidae family that are only found in Asia with widespread distribution across many countries including. Three species of Bungarus are found in China: Bungarus multicinctus (Chinese krait or many-banded krait), Bungarus fasciatus (banded krait) and Bungarus bungaroides (Himalayan krait) [1]. In China, B. multicinctus and B. fasciatus are more medically important because they are more common and, more likely to cause envenoming in humans. B. multicinctus is widely distributed in southern China [1], as well as in Myanmar, north Vietnam, Laos and Thailand [3]. B. multicinctus bites are ranked as the fifth most common in China, B. multicinctus envenoming is ranked first for case fatality rates, ranging from 26.9–33.3% depending on geographical location [2].
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