Impact of <i>Naja nigricollis</i> Venom on the Production of Methaemoglobin

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) acti...

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Main Authors: Harry F. Williams, Paul Hayter, Divyashree Ravishankar, Anthony Baines, Harry J. Layfield, Lorraine Croucher, Catherine Wark, Andrew B. Bicknell, Steven Trim, Sakthivel Vaiyapuri
Format: Article
Language:English
Published: MDPI AG 2018-12-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/10/12/539
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spelling doaj-0c50bdaf6b414ba68e46d8e750be24952020-11-24T21:23:02ZengMDPI AGToxins2072-66512018-12-01101253910.3390/toxins10120539toxins10120539Impact of <i>Naja nigricollis</i> Venom on the Production of MethaemoglobinHarry F. Williams0Paul Hayter1Divyashree Ravishankar2Anthony Baines3Harry J. Layfield4Lorraine Croucher5Catherine Wark6Andrew B. Bicknell7Steven Trim8Sakthivel Vaiyapuri9School of Pharmacy, University of Reading, Reading RG6 6UB, UKVenomtech, Discovery Park, Sandwich, Kent CT13 9ND, UKSchool of Pharmacy, University of Reading, Reading RG6 6UB, UKSchool of Biosciences, University of Kent, Kent CT2 7NZ, UKSchool of Pharmacy, University of Reading, Reading RG6 6UB, UKBMG LabTech, Buckinghamshire HP19 8JR, UKBMG LabTech, Buckinghamshire HP19 8JR, UKSchool of Biological Sciences, University of Reading, Reading RG6 6UB, UKVenomtech, Discovery Park, Sandwich, Kent CT13 9ND, UKSchool of Pharmacy, University of Reading, Reading RG6 6UB, UKSnakebite 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, <i>Naja nigricollis,</i> oxidises oxyhaemoglobin (Fe<sup>2+</sup>) into methaemoglobin (Fe<sup>3+</sup>) 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 <i>Naja nigricollis</i> 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.https://www.mdpi.com/2072-6651/10/12/539Snakebitevenommethaemoglobinhaemoglobinneglected tropical diseasespitting cobra
collection DOAJ
language English
format Article
sources DOAJ
author Harry F. Williams
Paul Hayter
Divyashree Ravishankar
Anthony Baines
Harry J. Layfield
Lorraine Croucher
Catherine Wark
Andrew B. Bicknell
Steven Trim
Sakthivel Vaiyapuri
spellingShingle Harry F. Williams
Paul Hayter
Divyashree Ravishankar
Anthony Baines
Harry J. Layfield
Lorraine Croucher
Catherine Wark
Andrew B. Bicknell
Steven Trim
Sakthivel Vaiyapuri
Impact of <i>Naja nigricollis</i> Venom on the Production of Methaemoglobin
Toxins
Snakebite
venom
methaemoglobin
haemoglobin
neglected tropical disease
spitting cobra
author_facet Harry F. Williams
Paul Hayter
Divyashree Ravishankar
Anthony Baines
Harry J. Layfield
Lorraine Croucher
Catherine Wark
Andrew B. Bicknell
Steven Trim
Sakthivel Vaiyapuri
author_sort Harry F. Williams
title Impact of <i>Naja nigricollis</i> Venom on the Production of Methaemoglobin
title_short Impact of <i>Naja nigricollis</i> Venom on the Production of Methaemoglobin
title_full Impact of <i>Naja nigricollis</i> Venom on the Production of Methaemoglobin
title_fullStr Impact of <i>Naja nigricollis</i> Venom on the Production of Methaemoglobin
title_full_unstemmed Impact of <i>Naja nigricollis</i> Venom on the Production of Methaemoglobin
title_sort impact of <i>naja nigricollis</i> venom on the production of methaemoglobin
publisher MDPI AG
series Toxins
issn 2072-6651
publishDate 2018-12-01
description 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, <i>Naja nigricollis,</i> oxidises oxyhaemoglobin (Fe<sup>2+</sup>) into methaemoglobin (Fe<sup>3+</sup>) 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 <i>Naja nigricollis</i> 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.
topic Snakebite
venom
methaemoglobin
haemoglobin
neglected tropical disease
spitting cobra
url https://www.mdpi.com/2072-6651/10/12/539
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