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Venom and Purified Toxins of the Spectacled Cobra (Naja naja) from Pakistan: Insights into Toxicity and Antivenom Neutralization.
Am J Trop Med Hyg. 2016 06 01; 94(6):1392-9.AJ

Abstract

Geographical variations of snake venoms can result in suboptimal effectiveness of Indian antivenoms that are currently used in most South Asian countries. This study investigated the toxicity and neutralization profile of the venom and toxins from Pakistani spectacled cobra, Naja naja, using VINS polyvalent antivenom (VPAV, India), Naja kaouthia monovalent antivenom (NKMAV, Thailand), and neuro bivalent antivenom (NBAV, Taiwan). Cation-exchange and reverse-phase high-performance liquid chromatography fractionations followed by toxin identification through liquid chromatography-mass spectrometry (MS)/MS indicated that the venom comprised mainly of postsynaptic neurotoxins (NTXs) (long neurotoxins [LNTXs], 28.3%; short neurotoxins [SNTXs], 8%), cytotoxins (CTXs) (31.2%), and acidic phospholipases A2 (12.3%). NKMAV is the most effective in neutralizing the lethal effect of the venom (potency = 1.1 mg venom/mL) and its LNTX (potency = 0.5 mg toxin/mL), consistent with the high content of LNTX in N. kaouthia venom. VPAV was effective in neutralizing the CTX (potency = 0.4 mg toxin/mL), in agreement with the higher CTX abundance in Indian cobra venom. All the three antivenoms were weak in neutralizing the SNTX (potency = 0.03-0.04 mg toxin/mL), including NBAV that was raised from the SNTX-rich Taiwanese cobra venom. In a challenge-rescue experiment, envenomed mice were prevented from death by a maximal dose of VPAV (intravenous 200 μL) but the recovery from paralysis was slow, indicating the need for higher or repeated doses of VPAV. Our results suggest that optimal neutralization for Pakistani N. naja venom may be achieved by improving the formulation of antivenom production to enhance antivenom immunoreactivity against long and SNTXs.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia tanch@um.edu tanngethong@yahoo.com.sg.Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia tanch@um.edu tanngethong@yahoo.com.sg.

Pub Type(s)

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

Language

eng

PubMed ID

27022154

Citation

Wong, Kin Ying, et al. "Venom and Purified Toxins of the Spectacled Cobra (Naja Naja) From Pakistan: Insights Into Toxicity and Antivenom Neutralization." The American Journal of Tropical Medicine and Hygiene, vol. 94, no. 6, 2016, pp. 1392-9.
Wong KY, Tan CH, Tan NH. Venom and Purified Toxins of the Spectacled Cobra (Naja naja) from Pakistan: Insights into Toxicity and Antivenom Neutralization. Am J Trop Med Hyg. 2016;94(6):1392-9.
Wong, K. Y., Tan, C. H., & Tan, N. H. (2016). Venom and Purified Toxins of the Spectacled Cobra (Naja naja) from Pakistan: Insights into Toxicity and Antivenom Neutralization. The American Journal of Tropical Medicine and Hygiene, 94(6), 1392-9. https://doi.org/10.4269/ajtmh.15-0871
Wong KY, Tan CH, Tan NH. Venom and Purified Toxins of the Spectacled Cobra (Naja Naja) From Pakistan: Insights Into Toxicity and Antivenom Neutralization. Am J Trop Med Hyg. 2016 06 1;94(6):1392-9. PubMed PMID: 27022154.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Venom and Purified Toxins of the Spectacled Cobra (Naja naja) from Pakistan: Insights into Toxicity and Antivenom Neutralization. AU - Wong,Kin Ying, AU - Tan,Choo Hock, AU - Tan,Nget Hong, Y1 - 2016/03/28/ PY - 2015/12/02/received PY - 2016/01/13/accepted PY - 2016/3/30/entrez PY - 2016/3/30/pubmed PY - 2017/5/10/medline SP - 1392 EP - 9 JF - The American journal of tropical medicine and hygiene JO - Am. J. Trop. Med. Hyg. VL - 94 IS - 6 N2 - Geographical variations of snake venoms can result in suboptimal effectiveness of Indian antivenoms that are currently used in most South Asian countries. This study investigated the toxicity and neutralization profile of the venom and toxins from Pakistani spectacled cobra, Naja naja, using VINS polyvalent antivenom (VPAV, India), Naja kaouthia monovalent antivenom (NKMAV, Thailand), and neuro bivalent antivenom (NBAV, Taiwan). Cation-exchange and reverse-phase high-performance liquid chromatography fractionations followed by toxin identification through liquid chromatography-mass spectrometry (MS)/MS indicated that the venom comprised mainly of postsynaptic neurotoxins (NTXs) (long neurotoxins [LNTXs], 28.3%; short neurotoxins [SNTXs], 8%), cytotoxins (CTXs) (31.2%), and acidic phospholipases A2 (12.3%). NKMAV is the most effective in neutralizing the lethal effect of the venom (potency = 1.1 mg venom/mL) and its LNTX (potency = 0.5 mg toxin/mL), consistent with the high content of LNTX in N. kaouthia venom. VPAV was effective in neutralizing the CTX (potency = 0.4 mg toxin/mL), in agreement with the higher CTX abundance in Indian cobra venom. All the three antivenoms were weak in neutralizing the SNTX (potency = 0.03-0.04 mg toxin/mL), including NBAV that was raised from the SNTX-rich Taiwanese cobra venom. In a challenge-rescue experiment, envenomed mice were prevented from death by a maximal dose of VPAV (intravenous 200 μL) but the recovery from paralysis was slow, indicating the need for higher or repeated doses of VPAV. Our results suggest that optimal neutralization for Pakistani N. naja venom may be achieved by improving the formulation of antivenom production to enhance antivenom immunoreactivity against long and SNTXs. SN - 1476-1645 UR - https://www.unboundmedicine.com/medline/citation/27022154/Venom_and_Purified_Toxins_of_the_Spectacled_Cobra__Naja_naja__from_Pakistan:_Insights_into_Toxicity_and_Antivenom_Neutralization_ L2 - http://www.ajtmh.org/content/journals/10.4269/ajtmh.15-0871?crawler=true&mimetype=application/pdf DB - PRIME DP - Unbound Medicine ER -
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