Abstract
Bitis arietans is a snake of medical importance, as it is responsible for more accidents in humans and domestic animals than all other African snakes put together. The accidents are characterized by local and systemic alterations, such as inflammation, cardiovascular and hemostatic disturbances, which can lead victims to death or permanent disability. However, little is known about the envenomation mechanism, especially regarding the inflammatory response, which is related to severe clinical conditions triggered by the venom. Therefore, the aim of the present study was to evaluate the inflammatory response related to the B. arietans envenomation using a peritonitis mice model. By pharmacological interventions and use of mice genetically deficient of the 5-lipoxygenase enzyme (5-LO−/−) or platelet-activating factor (PAF) receptor (PAFR−/− the participation of eicosanoids and PAF in this response was also investigated. The obtained results demonstrated that the venom induces an in vivo inflammatory response, characterized by an early increased vascular permeability, followed by an accumulation of polymorphonuclear (PMN) cells in the peritoneal cavity, accompanied by the production of the eicosanoids LTB4, LTC4, TXB2 and PGE2, as well as the local and systemic production of IL-6 and MCP-1. These inflammatory events were attenuated by the pre-treatment with anti-inflammatory drugs that interfere in lipid mediators’ functions. However, 5-LO−/− mice did not show a reduction of inflammatory response induced by the venom, while PAFR−/− mice showed a reduction in both the PMN leukocytes number and the local and systemic production of IL-6 and MCP-1. This study demonstrated that the Bitis arietans venom contains toxins that trigger an inflammatory process, which is partially dependent on lipid mediators, and may contribute to the envenomation pathology.
Highlights
Snakebite is a serious and neglected public health problem worldwide, especially in tropical and subtropical countries in Asia, Africa, Oceania and Latin America [1,2,3]
This study demonstrated that the Bitis arietans venom contains toxins that trigger an inflammatory process, which is partially dependent on lipid mediators, and may contribute to the envenomation pathology
The use of the Bitis arietans venom as an inflammation inducer, the peritoneal cavity as the anatomical site, and the 129 SvE and C57BL/6 mice as animal models in this study were all motivated by the following: (a) B. arietans is a snake widely distributed throughout Sub-Saharan Africa, and Morocco and West Arabia [1,2,3,30,31]; (b) the envenomation causes inflammation, and severe local and systemic symptoms, which may lead to death [4]; (c) the peritoneal cavity was chosen for analysis of B. arietans venom (BaV)-inducing inflammation due to its viability as an experimental model; (d) the use of 129 SvE mice limits the genetic influence, while the use of C57BL/6 generalizes the obtained results; (e) the total venom was used to get an overview of the whole process
Summary
Snakebite is a serious and neglected public health problem worldwide, especially in tropical and subtropical countries in Asia, Africa, Oceania and Latin America [1,2,3]. In Sub-Saharan Africa alone, an average of 250,000 snake envenomations per year is estimated, with more than 17,000 deaths [1], besides several morbidities, including local tissue damage, amputations and chronic disabilities [2]. Toxins 2020, 12, 594 body size and venom rich in a variety of toxins explain its medical importance [4,5,6,7,8]. This snake is responsible for more accidents and deaths, in humans and domestic animals, than all other African snakes [4].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
