Tags

Type your tag names separated by a space and hit enter

Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models.
PLoS Negl Trop Dis. 2020 02; 14(2):e0008054.PN

Abstract

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.

Authors+Show Affiliations

Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.Department of Emergency Medicine, En Chu Kong Hospital, New Taipei City, Taiwan.Department of Emergency Medicine, En Chu Kong Hospital, New Taipei City, Taiwan.Faculty of Biotechnology and Laboratory Science in Medicine, School of Medical Technology and Engineering, National Yang-Ming University, Taipei, Taiwan.Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan. Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.Department of Emergency Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.Department of Emergency Medicine, Yeezen General Hospital, Taoyuan, Taiwan.Department of Emergency Medicine, En Chu Kong Hospital, New Taipei City, Taiwan. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.Department of Emergency Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32032357

Citation

Liu, Chien-Chun, et al. "Pathogenesis of Local Necrosis Induced By Naja Atra Venom: Assessment of the Neutralization Ability of Taiwanese Freeze-dried Neurotoxic Antivenom in Animal Models." PLoS Neglected Tropical Diseases, vol. 14, no. 2, 2020, pp. e0008054.
Liu CC, Chou YS, Chen CY, et al. Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models. PLoS Negl Trop Dis. 2020;14(2):e0008054.
Liu, C. C., Chou, Y. S., Chen, C. Y., Liu, K. L., Huang, G. J., Yu, J. S., Wu, C. J., Liaw, G. W., Hsieh, C. H., & Chen, C. K. (2020). Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models. PLoS Neglected Tropical Diseases, 14(2), e0008054. https://doi.org/10.1371/journal.pntd.0008054
Liu CC, et al. Pathogenesis of Local Necrosis Induced By Naja Atra Venom: Assessment of the Neutralization Ability of Taiwanese Freeze-dried Neurotoxic Antivenom in Animal Models. PLoS Negl Trop Dis. 2020;14(2):e0008054. PubMed PMID: 32032357.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models. AU - Liu,Chien-Chun, AU - Chou,Yu-Shao, AU - Chen,Chun-Yu, AU - Liu,Kuei-Lin, AU - Huang,Guo-Jen, AU - Yu,Jau-Song, AU - Wu,Cho-Ju, AU - Liaw,Geng-Wang, AU - Hsieh,Cheng-Hsien, AU - Chen,Chun-Kuei, Y1 - 2020/02/07/ PY - 2019/09/01/received PY - 2020/01/14/accepted PY - 2020/02/20/revised PY - 2020/2/8/pubmed PY - 2020/4/28/medline PY - 2020/2/8/entrez SP - e0008054 EP - e0008054 JF - PLoS neglected tropical diseases JO - PLoS Negl Trop Dis VL - 14 IS - 2 N2 - 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. SN - 1935-2735 UR - https://www.unboundmedicine.com/medline/citation/32032357/Pathogenesis_of_local_necrosis_induced_by_Naja_atra_venom:_Assessment_of_the_neutralization_ability_of_Taiwanese_freeze_dried_neurotoxic_antivenom_in_animal_models_ L2 - https://dx.plos.org/10.1371/journal.pntd.0008054 DB - PRIME DP - Unbound Medicine ER -