In Vitro Neurotoxicity of Chinese Krait (Bungarus multicinctus) Venom and Neutralization by Antivenoms

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.

In Vitro Toxicity of Chinese Russell’s Viper (Daboia siamensis) Venom and Neutralisation by Antivenoms

“…The t 50 values and the inhibition of indirect twitches in vitro by Chinese D. siamensis suggest relatively weak neurotoxic effects compared to venom from Sri Lankan D. russelii [ 10 ] and ‘neurotoxic’ venoms more broadly [ 10 , 30 , 31 , 32 ]. Venoms that display the rapid inhibition of indirect twitches in skeletal muscle preparations (e.g., many elapid venoms; [ 30 , 31 , 32 ]) generally contain an abundance of short-chain α-neurotoxins.…”

“…The t 50 values and the inhibition of indirect twitches in vitro by Chinese D. siamensis suggest relatively weak neurotoxic effects compared to venom from Sri Lankan D. russelii [ 10 ] and ‘neurotoxic’ venoms more broadly [ 10 , 30 , 31 , 32 ]. Venoms that display the rapid inhibition of indirect twitches in skeletal muscle preparations (e.g., many elapid venoms; [ 30 , 31 , 32 ]) generally contain an abundance of short-chain α-neurotoxins. These rapidly acting toxins, which inhibit the binding of the neurotransmitter to the skeletal muscle nicotinic receptor, contribute to the very low t 50 /t 90 values in comparison to venoms which lack α-neurotoxins.…”

Investigation of target genes and potential mechanisms related to compound Xiao-ai-fei honey ointment based on network pharmacology and bioinformatics analysis

“…[4][5][6] According to the literature, CXHO is made of several bioactive components, including Bungarus multicinctus, Piperis Longi Fructus, Rhizoma Alpiniae Officinarum, Piper nigrum L, and Zingiber officinale Roseco. [7][8][9][10][11] B multicinctus (Bm), the juvenile snake dried body of the Chinese krait, [12] contains more than 20 elements, [13] and has been used to treat rheumatic disease, tetanus and leprosy, [14] due to its anti-inflammatory and analgesic effects. [15] Piperis Longi Fructus (PLF), which is made from the mature and immature fruit of Piper longum L, [16] has been widely used in traditional Chinese medicine (TCM) and Indian medicine.…”

“…B multicinctus (Bm), the juvenile snake dried body of the Chinese krait, [12] contains more than 20 elements, [13] and has been used to treat rheumatic disease, tetanus and leprosy, [14] due to its anti-inflammatory and analgesic effects. [15] Piperis Longi Fructus (PLF), which is made from the mature and immature fruit of Piper longum L, [16] has been widely used in traditional Chinese medicine (TCM) and Indian medicine.…”

Glutamine ameliorates Bungarus multicinctus venom-induced lung and heart injury through HSP70: NF-κB p65 and P53/PUMA signaling pathways involved

“…Although antivenom has a high ability to neutralize free snake venom, it cannot neutralize toxins that are bound to cardiopulmonary tissue cells. Further progression of cardiopulmonary injury is prone to MOF [ 8 , 14 ]. Therefore, it is necessary to investigate the treatment of the cardiopulmonary injury caused by Bungarus multicinctus venom in order to inhibit the development of snakebite syndrome.…”