Analysis of the necrosis-inducing components of the venom of naja atra and assessment of the neutralization ability of freeze-dried antivenom

Cheng Hsuan Ho, Liao Chun Chiang, Yan Chiao Mao, Kuo Cheng Lan, Shih Hung Tsai, Yu Jen Shih, Yuan Sheng Tzeng, Chin Sheng Lin, Wen Loung Lin, Wei Hsuan Fang, Kuang Ting Chen, Chi Hsin Lee, Dapi Meng Lin Chiang, Shing Hwa Liu

研究成果: 雜誌貢獻文章同行評審

摘要

Patients bitten by Naja atra who are treated with bivalent freeze-dried neurotoxic antivenom in Taiwan have an improved survival rate but develop necrotic wound changes. The World Health Organization (WHO) has suggested using the minimum necrotizing dose (MND) of venom as a method of evaluating the neutralization effect of antivenom. The aim of this study was to evaluate the effectiveness of antivenom for the prevention of necrosis based on the MND and clarify which component of the venom of N. atra induces necrosis. The neurotoxins (NTXs) were removed from the crude venom (deNTXs), and different concentrations of deNTXs were injected intradermally into the dorsal skin of mice. After three days, the necrotic lesion diameter was found to be approximately 5 mm, and the MND was calculated. A reduction in the necrotic diameter of 50% was used to identify the MND50. Furthermore, both phospholipase A2 (PLA2) and cytotoxins (CTXs) were separately removed from the deNTXs to identify the major necrosis-inducing factor, and the necrotic lesions were scored. All mice injected with deNTXs survived for three days and developed necrotic wounds. The MND of the deNTXs for mice was 0.494 ± 0.029 µg/g, that of the deNTXsdePLA2 (major component retained: CTXs) was 0.294 ± 0.05 µg/g, and that of the deNTX-deCTX (major component retained: PLA2) venom was greater than 1.25 µg/g. These values show that CTX is the major factor inducing necrosis. These results suggest that the use of the deNTXs is necessary to enable the mice to survive long enough to develop venom-induced cytolytic effects. CTXs play a major role in N. atra-related necrosis. However, the MND50 could not be identified in this study, which meant that the antivenom did not neutralize venom-induced necrosis.
原文英語
文章編號619
期刊Toxins
13
發行號9
DOIs
出版狀態已發佈 - 9月 2021

ASJC Scopus subject areas

  • 毒理學
  • 健康、毒理學和誘變

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