Citation

Wong KY, Tan CH, Tan NH. Am. J. Trop. Med. Hyg. 2016; 94(6): 1392-1399.

Affiliation

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.

Copyright

(Copyright © 2016, American Society of Tropical Medicine and Hygiene, Publisher American Society of Tropical Medicine)

DOI

10.4269/ajtmh.15-0871

PMID

27022154

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 kaouthiamonovalent 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 inN. kaouthiavenom. 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 PakistaniN. najavenom may be achieved by improving the formulation of antivenom production to enhance antivenom immunoreactivity against long and SNTXs.

© The American Society of Tropical Medicine and Hygiene.

Language: en