Neurotoxicity Research

, Volume 31, Issue 1, pp 11–19 | Cite as

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

  • Anjana Silva
  • Sanjaya Kuruppu
  • Iekhsan Othman
  • Robert J.A. Goode
  • Wayne C. Hodgson
  • Geoffrey K. Isbister
Original Article

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 t90 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.

Keywords

Russell’s viper Neurotoxicity Pre-synaptic Phospholipase A2 

Notes

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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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Monash Venom Group, Department of Pharmacology, Biomedicine Discovery InstituteMonash UniversityMelbourneAustralia
  2. 2.Department of Parasitology, Faculty of Medicine and Allied SciencesRajarata University of Sri LankaSaliyapuraSri Lanka
  3. 3.Department of Biochemistry and Molecular Biology, Biomedicine Discovery InstituteMonash UniversityMelbourneAustralia
  4. 4.Jeffrey Cheah School of MedicineMonash University MalaysiaBandar SunwayMalaysia
  5. 5.Clinical Toxicology Research Group, Faculty of Health and MedicineUniversity of NewcastleWaratahAustralia

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