{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:23:00Z","timestamp":1793276580457,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:00:00Z","timestamp":1630540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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 \u00b1 0.029 \u00b5g\/g, that of the deNTXs-dePLA2 (major component retained: CTXs) was 0.294 \u00b1 0.05 \u00b5g\/g, and that of the deNTX-deCTX (major component retained: PLA2) venom was greater than 1.25 \u00b5g\/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.<\/jats:p>","DOI":"10.3390\/toxins13090619","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T23:55:22Z","timestamp":1630972522000},"page":"619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Analysis of the Necrosis-Inducing Components of the Venom of Naja atra and Assessment of the Neutralization Ability of Freeze-Dried Antivenom"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8692-2572","authenticated-orcid":false,"given":"Cheng-Hsuan","family":"Ho","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"},{"name":"Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liao-Chun","family":"Chiang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, National Tsing Hua University, Hsinchu 300, Taiwan"},{"name":"Institute of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8561-0582","authenticated-orcid":false,"given":"Yan-Chiao","family":"Mao","sequence":"additional","affiliation":[{"name":"Division of Clinical Toxicology, Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Cheng","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0215-3193","authenticated-orcid":false,"given":"Shih-Hung","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jen","family":"Shih","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8440-2351","authenticated-orcid":false,"given":"Yuan-Sheng","family":"Tzeng","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5167-8327","authenticated-orcid":false,"given":"Chin-Sheng","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Loung","family":"Lin","sequence":"additional","affiliation":[{"name":"Taichung Wildlife Conservation Group, Taichung 436, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Hsuan","family":"Fang","sequence":"additional","affiliation":[{"name":"Taichung Wildlife Conservation Group, Taichung 436, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang-Ting","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine, Chang Bing Show Chwan Memorial Hospital, Changhua 505, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3412-7400","authenticated-orcid":false,"given":"Chi-Hsin","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dapi Meng-Lin","family":"Chiang","sequence":"additional","affiliation":[{"name":"Division of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University Munich, 85354 Freising, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9976-1197","authenticated-orcid":false,"given":"Shing-Hwa","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 100, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan"},{"name":"Department of Pediatrics, College of Medicine, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gopalakrishnakone, P. 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