Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models.
Naja atra envenomation is one of the most significant clinical snakebite concerns in Taiwan. Taiwanese freeze-dried neurotoxic antivenom (FNAV) is currently used clinically for the treatment of cobra snakebite, and has been shown to limit the mortality of cobra envenomation to less than 1%. However,...
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ftdoajarticles:oai:doaj.org/article:49125d4ef0ab4221b3c5cec3e9cc3cfc 2023-05-15T15:13:25+02:00 Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models. Chien-Chun Liu Yu-Shao Chou Chun-Yu Chen Kuei-Lin Liu Guo-Jen Huang Jau-Song Yu Cho-Ju Wu Geng-Wang Liaw Cheng-Hsien Hsieh Chun-Kuei Chen 2020-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008054 https://doaj.org/article/49125d4ef0ab4221b3c5cec3e9cc3cfc EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008054 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008054 https://doaj.org/article/49125d4ef0ab4221b3c5cec3e9cc3cfc PLoS Neglected Tropical Diseases, Vol 14, Iss 2, p e0008054 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008054 2022-12-31T07:56:49Z Naja atra envenomation is one of the most significant clinical snakebite concerns in Taiwan. Taiwanese freeze-dried neurotoxic antivenom (FNAV) is currently used clinically for the treatment of cobra snakebite, and has been shown to limit the mortality of cobra envenomation to less than 1%. However, more than half of victims (60%) require surgery because of local tissue necrosis, a major problem in patients with cobra envenomation. Although the importance of evaluating the neutralizing effect of FNAV on this pathology is recognized, whether FNAV is able to prevent the local necrosis extension induced by N. atra venom has not been investigated in detail. Cytotoxins (CTXs) are considered as the major components of N. atra venom that cause necrosis. In the current study, we isolated CTXs from whole cobra venom and used both whole venom and purified CTXs to develop animal models for assessing the neutralization potential of FNAV against venom necrotizing activity. Local necrotic lesions were successfully produced in mice using CTXs in place of whole N. atra venom. FNAV was able to rescue mice from a subcutaneously injected lethal dose of cobra venom; however, it was unable to prevent CTX-induced dermo-necrosis. Furthermore, using the minimal necrosis dose (MND) of CTXs and venom proteome data, we found a dose of whole N. atra venom suitable for FNAV and developed a workable protocol for inducing local necrosis in rodent models that successfully imitated the clinical circumstance of cobra envenoming. This information provides a more comprehensive understanding of the pathophysiology of N. atra envenomation, and serves as a guide for improving current antivenom strategies and advancing clinical snakebite management in Taiwan. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 2 e0008054 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Chien-Chun Liu Yu-Shao Chou Chun-Yu Chen Kuei-Lin Liu Guo-Jen Huang Jau-Song Yu Cho-Ju Wu Geng-Wang Liaw Cheng-Hsien Hsieh Chun-Kuei Chen Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Naja atra envenomation is one of the most significant clinical snakebite concerns in Taiwan. Taiwanese freeze-dried neurotoxic antivenom (FNAV) is currently used clinically for the treatment of cobra snakebite, and has been shown to limit the mortality of cobra envenomation to less than 1%. However, more than half of victims (60%) require surgery because of local tissue necrosis, a major problem in patients with cobra envenomation. Although the importance of evaluating the neutralizing effect of FNAV on this pathology is recognized, whether FNAV is able to prevent the local necrosis extension induced by N. atra venom has not been investigated in detail. Cytotoxins (CTXs) are considered as the major components of N. atra venom that cause necrosis. In the current study, we isolated CTXs from whole cobra venom and used both whole venom and purified CTXs to develop animal models for assessing the neutralization potential of FNAV against venom necrotizing activity. Local necrotic lesions were successfully produced in mice using CTXs in place of whole N. atra venom. FNAV was able to rescue mice from a subcutaneously injected lethal dose of cobra venom; however, it was unable to prevent CTX-induced dermo-necrosis. Furthermore, using the minimal necrosis dose (MND) of CTXs and venom proteome data, we found a dose of whole N. atra venom suitable for FNAV and developed a workable protocol for inducing local necrosis in rodent models that successfully imitated the clinical circumstance of cobra envenoming. This information provides a more comprehensive understanding of the pathophysiology of N. atra envenomation, and serves as a guide for improving current antivenom strategies and advancing clinical snakebite management in Taiwan. |
format |
Article in Journal/Newspaper |
author |
Chien-Chun Liu Yu-Shao Chou Chun-Yu Chen Kuei-Lin Liu Guo-Jen Huang Jau-Song Yu Cho-Ju Wu Geng-Wang Liaw Cheng-Hsien Hsieh Chun-Kuei Chen |
author_facet |
Chien-Chun Liu Yu-Shao Chou Chun-Yu Chen Kuei-Lin Liu Guo-Jen Huang Jau-Song Yu Cho-Ju Wu Geng-Wang Liaw Cheng-Hsien Hsieh Chun-Kuei Chen |
author_sort |
Chien-Chun Liu |
title |
Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models. |
title_short |
Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models. |
title_full |
Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models. |
title_fullStr |
Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models. |
title_full_unstemmed |
Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models. |
title_sort |
pathogenesis of local necrosis induced by naja atra venom: assessment of the neutralization ability of taiwanese freeze-dried neurotoxic antivenom in animal models. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008054 https://doaj.org/article/49125d4ef0ab4221b3c5cec3e9cc3cfc |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 2, p e0008054 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008054 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008054 https://doaj.org/article/49125d4ef0ab4221b3c5cec3e9cc3cfc |
op_doi |
https://doi.org/10.1371/journal.pntd.0008054 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
14 |
container_issue |
2 |
container_start_page |
e0008054 |
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1766343968740605952 |