School of Pharmacy, University of Reading, Reading RG6 6UB, UK.
Venomtech, Discovery Park, Sandwich, Kent CT13 9ND, UK.
Toxins (Basel). 2018 Dec 15;10(12):539. doi: 10.3390/toxins10120539.
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, oxidises oxyhaemoglobin (Fe) into methaemoglobin (Fe) 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 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.
蛇咬伤中毒目前估计每年导致超过 10 万人死亡。由于世界各地观察到毒液成分的巨大变化,蛇咬伤与多种病理生理学有关。蛇毒液的溶血作用(即红细胞溶解)已有充分记录,尽管毒液对血红蛋白的直接影响尚未完全了解。在这里,我们报告了多种蛇毒液将血红蛋白氧化成高铁血红蛋白的不同能力。此外,我们的结果表明,一种眼镜蛇科的毒蛇,黑颈喷毒眼镜蛇的毒液以时间和浓度依赖的方式将氧合血红蛋白(Fe)氧化成高铁血红蛋白(Fe),这在评估的 47 种蝰蛇和眼镜蛇毒液中是无与伦比的。用还原剂二硫苏糖醇(DTT)处理毒液可观察到在较高浓度下增强这种作用,而变性毒液的使用表明这种作用依赖于毒液中热敏感的蛋白质成分。总之,我们的结果表明,毒液似乎促进高铁血红蛋白的产生程度在眼镜蛇科中很少见,并且这种活性似乎独立于毒液成分对血红蛋白的蛋白水解活性。