Vol.:(0123456789) 1 3 Archives of Toxicology https://doi.org/10.1007/s00204-019-02619-y BIOLOGICS Comparative study of the in vivo toxicity and pathophysiology of envenomation by three medically important Egyptian snake venoms Tarek M. Abd El‑Aziz 1,2  · Mahmoud I. Shoulkamy 2,3  · Ahmed M. Hegazy 2  · James D. Stockand 1  · Ahmed Mahmoud 4  · Ashraf M. A. Mashaly 2 Received: 3 September 2019 / Accepted: 6 November 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Snakebite envenomation is a serious medical problem in many developing tropical and subtropical countries. Envenomation is registered by the World Health Organization as a neglected tropical disease due to critical shortages in the production of antivenom. Envenomation causes more than 100,000 deaths annually. Snakebites result in several efects to include edema, blistering, hemorrhage, necrosis and respiratory paralysis. Antivenom is the preferred treatment for the systemic efects of snakebite envenomation, though these are often inefective in neutralizing venom toxin-induced local tissue damage. To efectively treat snakebites, it is important to determine the lethal potency and pathophysiological efects induced by specifc snake venoms. In the current study, we compared the lethality, and the hemorrhagic and dermonecrotic activities of ven- oms from three snakes in Egypt that are the primary causes of local tissue necrosis. Our data show that the intraperitoneal median lethal doses (LD 50 ) for Cerastes cerastes, Echis carinatus and Naja nigricollis venoms are 0.946, 1.744 and 0.341 mg/kg mouse body weight, respectively. These results indicated that N. nigricollis venom is the most toxic and signifcantly accelerated the time of death compared to the other two venoms. However, no hematoma or associated edema appeared upon sub-plantar injection of N. nigricollis venom into the mice hind paw. Two hours following intradermal injection of C. cerastes and E. carinatus venoms, macroscopic analysis of the inner surface of mouse skin showed severe hemorrhagic lesions, whereas only insignifcant hemorrhagic lesion appeared in mice injected with the highest dose of N. nigricollis venom. Furthermore, the minimum necrotic doses (MND) for the same venoms were 43.15, and 70.87 µg/mouse, or not observed in the case of N. nigricollis venom, respectively. These LD 50 values and pathophysiological results can be used to guide development of antivenom against bites by these dangerous Egyptian snakes. Keywords Snake venoms · Snakebites · Envenomation · In vivo toxicity · Pathophysiology · Hemorrhage · Antivenom production Introduction The frequency and mortality of snakebites pose a serious burden in the rural communities of poor and develop- ing countries. Globally, venomous snakes bite more than Tarek M. Abd El-Aziz and Mahmoud I. Shoulkamy contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00204-019-02619-y) contains supplementary material, which is available to authorized users. * Tarek M. Abd El-Aziz mohamedt1@uthscsa.edu 1 Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA 2 Zoology Department, Faculty of Science, Minia University, El-Minia 61519, Egypt 3 Guangdong Key Laboratory of Genome Stability & Disease Prevention, Shenzhen University School of Medicine, Shenzhen 518060, Guangdong, China 4 Department of Zoology, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia