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Neurotoxicity in Sri Lankan Russell’s Viper (Daboia russelii) Envenoming is Primarily due to U1-viperitoxin-Dr1a, a Pre-Synaptic Neurotoxin

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Abstract

Russell’s vipers are snakes of major medical importance in Asia. Russell’s viper (Daboia russelii) envenoming in Sri Lanka and South India leads to a unique, mild neuromuscular paralysis, not seen in other parts of the world where the snake is found. This study aimed to identify and pharmacologically characterise the major neurotoxic components of Sri Lankan Russell’s viper venom. Venom was fractionated using size exclusion chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC). In vitro neurotoxicities of the venoms, fractions and isolated toxins were measured using chick biventer and rat hemidiaphragm preparations. A phospholipase A2 (PLA2) toxin, U1-viperitoxin-Dr1a (13.6 kDa), which constitutes 19.2 % of the crude venom, was isolated and purified using HPLC. U1-viperitoxin-Dr1a produced concentration-dependent in vitro neurotoxicity abolishing indirect twitches in the chick biventer nerve-muscle preparation, with a t 90 of 55 ± 7 min only at 1 μM. The toxin did not abolish responses to acetylcholine and carbachol indicating pre-synaptic neurotoxicity. Venom, in the absence of U1-viperitoxin-Dr1a, did not induce in vitro neurotoxicity. Indian polyvalent antivenom, at the recommended concentration, only partially prevented the neurotoxic effects of U1-viperitoxin-Dr1a. Liquid chromatography mass spectrometry analysis confirmed that U1-viperitoxin-Dr1a was the basic S-type PLA2 toxin previously identified from this venom (NCBI—GI: 298351762; SwissProt: P86368). The present study demonstrates that neurotoxicity following Sri Lankan Russell’s viper envenoming is primarily due to the pre-synaptic neurotoxin U1-viperitoxin-Dr1a. Mild neurotoxicity observed in severely envenomed Sri Lankan Russell’s viper bites is most likely due to the low potency of U1-viperitoxin-Dr1a, despite its high relative abundance in the venom.

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Acknowledgments

We thank Ariaranee Gnanadasan (Faculty of Medicine – University of Colombo) for kindly supplying Sri Lankan Russell’s viper venom for this study. Daniela Kniesz (Monash Venom Group) is acknowledged for various assistances in chromatography. GKI is funded by a National Health and Medical Research Council – Australia (NHMRC) Senior Research Fellowship (ID: 1061041) and NHMRC Centres for Research Excellence Grant ID: 1110343.

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Authors and Affiliations

  1. Monash Venom Group, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, 3800, Australia

    Anjana Silva, Sanjaya Kuruppu, Wayne C. Hodgson & Geoffrey K. Isbister

  2. Department of Parasitology, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, 50008, Sri Lanka

    Anjana Silva

  3. Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton Campus, Melbourne, VIC, 3800, Australia

    Sanjaya Kuruppu & Robert J.A. Goode

  4. Jeffrey Cheah School of Medicine, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia

    Iekhsan Othman

  5. Clinical Toxicology Research Group, Faculty of Health and Medicine, University of Newcastle, Level 5, New Med Building, Calvary Mater Hospital, Edith Street, Waratah, NSW, 2298, Australia

    Geoffrey K. Isbister

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  1. Anjana Silva
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  2. Sanjaya Kuruppu
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  3. Iekhsan Othman
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  4. Robert J.A. Goode
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  5. Wayne C. Hodgson
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  6. Geoffrey K. Isbister
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Correspondence to Anjana Silva.

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Silva, A., Kuruppu, S., Othman, I. et al. Neurotoxicity in Sri Lankan Russell’s Viper (Daboia russelii) Envenoming is Primarily due to U1-viperitoxin-Dr1a, a Pre-Synaptic Neurotoxin. Neurotox Res 31, 11–19 (2017). https://doi.org/10.1007/s12640-016-9650-4

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  • DOI: https://doi.org/10.1007/s12640-016-9650-4

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