Impact of Naja nigricollis Venom on the Production of Methaemoglobin.

Harry Williams,Harry Layfield,Divyashree Ravishankar,Anthony Baines,Andrew Bicknell,Sakthivel Vaiyapuri,Steven Trim,Catherine Wark,Paul Hayter,Lorraine Croucher

doi:10.3390/toxins10120539

Harry Williams, Harry Layfield + Show 8 more

Open Access

https://doi.org/10.3390/toxins10120539

Copy DOI

Journal: Toxins	Publication Date: Dec 15, 2018
Citations: 13	License type: CC BY 4.0

Affiliation: University of Reading, University of Kent

Abstract

Snakebite envenomation is an affliction currently estimated to be killing upwards of 100,000 people annually. Snakebite is associated with a diverse pathophysiology due to the magnitude of variation in venom composition that is observed worldwide. The haemolytic (i.e., lysis of red blood cells) actions of snake venoms are well documented, although the direct impact of venoms on haemoglobin is not fully understood. Here we report on the varied ability of a multitude of snake venoms to oxidise haemoglobin into methaemoglobin. Moreover, our results demonstrate that the venom of an elapid, the black necked spitting cobra, Naja nigricollis, oxidises oxyhaemoglobin (Fe2+) into methaemoglobin (Fe3+) in a time- and concentration-dependent manner that is unparalleled within the 47 viper and elapid venoms evaluated. The treatment of venom with a reducing agent, dithiothreitol (DTT) is observed to potentiate this effect at higher concentrations, and the use of denatured venom demonstrates that this effect is dependent upon the heat-sensitive proteinaceous elements of the venom. Together, our results suggest that Naja nigricollis venom appears to promote methaemoglobin production to a degree that is rare within the Elapidae family, and this activity appears to be independent of proteolytic activities of venom components on haemoglobin.

Highlights

Snakebite envenomation is considered to be a major neglected tropical disease
The ability of venoms to oxidise Hb into MetHb has been reported within the family of Viperidae impact of these on MetHb production
The proteins found within the snake venoms have a multitude of pharmacological actions including direct effects on cells

Summary

Introduction

Snakebite envenomation is considered to be a major neglected tropical disease. It is estimated to affect nearly five million people and result in approximately 100,000 deaths annually [1]. Despite the significant impact on the health and well-being of humans, much remains unknown about the different toxic proteins and peptides that are the major components of snake venoms [4]. Toxins 2018, 10, 539 families and sub families, but the vast majority of deaths occur as a result of bites from those found in Viperidae (Vipers) and Elapidae (Elapids). These two families are very different; vipers are typically ambush predators that inject a venom composed mainly of large proteins that predominantly affect haemostasis, while elapids are generally more active hunters, with venoms containing fewer of these haemotoxic components but instead dominated by neurotoxic and cytotoxic proteins and peptides [5]

Methods

Results

Conclusion