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  4. Analysis of the Necrosis-Inducing Components of the Venom of Naja atra and Assessment of the Neutralization Ability of Freeze-Dried Antivenom
 
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Analysis of the Necrosis-Inducing Components of the Venom of Naja atra and Assessment of the Neutralization Ability of Freeze-Dried Antivenom

Journal
Toxins
Journal Volume
13
Journal Issue
9
Date Issued
2021-09-02
Author(s)
Ho, Cheng-Hsuan
Chiang, Liao-Chun
Mao, Yan-Chiao
Lan, Kuo-Cheng
Tsai, Shih-Hung
Shih, Yu-Jen
Tzeng, Yuan-Sheng
Lin, Chin-Sheng
Lin, Wen-Loung
Fang, Wei-Hsuan
Chen, Kuang-Ting
Lee, Chi-Hsin
Chiang, Dapi Meng-Lin
SHING-HWA LIU  
DOI
10.3390/toxins13090619
URI
https://scholars.lib.ntu.edu.tw/handle/123456789/628618
URL
https://api.elsevier.com/content/abstract/scopus_id/85114333649
Abstract
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 deNTXs-dePLA2 (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.
Subjects
Naja atra; minimum necrotizing dose; snake
Publisher
MDPI
Type
journal article

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