Crosstalk of Inflammation and Coagulation in Bothrops Snakebite Envenoming: Endogenous Signaling Pathways and Pathophysiology

Abstract

Snakebite envenoming represents a major health problem in tropical and subtropical countries. Considering the elevated number of accidents and high morbidity and mortality rates, the World Health Organization reclassified this disease to category A of neglected diseases. In Latin America, Bothrops genus snakes are mainly responsible for snakebites in humans, whose pathophysiology is characterized by local and systemic inflammatory and degradative processes, triggering prothrombotic and hemorrhagic events, which lead to various complications, organ damage, tissue loss, amputations, and death. The activation of the multicellular blood system, hemostatic alterations, and activation of the inflammatory response are all well-documented in Bothrops envenomings. However, the interface between inflammation and coagulation is still a neglected issue in the toxinology field. Thromboinflammatory pathways can play a significant role in some of the major complications of snakebite envenoming, such as stroke, venous thromboembolism, and acute kidney injury. In addition to exacerbating inflammation and cell interactions that trigger vaso-occlusion, ischemia–reperfusion processes, and, eventually, organic damage and necrosis. In this review, we discuss the role of inflammatory pathways in modulating coagulation and inducing platelet and leukocyte activation, as well as the inflammatory production mediators and induction of innate immune responses, among other mechanisms that are altered by Bothrops venoms.

Unveiling the Pain Relief Potential: Harnessing Analgesic Peptides from Animal Venoms

“…Some venoms are able to induce pain [ 6 , 42 ], edema, local and systemic inflammatory process [ 50 , 51 , 52 ], oxidative stress [ 53 ], the functional destabilization of the coagulation system [ 54 , 55 ], acute kidney injury [ 56 ], rhabdomyolysis, and necrosis. In addition, other snake venoms can trigger a neurotoxic syndrome: flaccid paralysis (bilateral ptosis and ophthalmoplegia) and flaccid neuromuscular paralysis (descending), which can be aggravated by involving the bulbar blockade (mouth and throat muscles responsible for speech and swallowing) and respiratory muscles [ 57 ].…”

Bothrops lanceolatus Envenoming in Martinique: A Historical Perspective of the Clinical Effectiveness of Bothrofav Antivenom Treatment

“…snake envenomation include marked local damage which may be associated in some severe cases with abnormal hemostasis with systemic hemorrhage. Coagulotoxicity has been attributed to the synergistic action of several venom toxins [ 1 , 2 , 3 ]. The most toxic constituents of Bothrops spp.…”

“…The mechanisms behind the thrombotic effect induced by B. lanceolatus venom are largely unknown. Proposed mechanisms of these thrombotic events include direct injury to the vascular endothelium by venom toxins and vascular endothelial cell activation related to inflammatory processes [ 2 , 13 , 14 ]. Notably, the proteomic and toxicological profiles of B. lanceolatus venom are similar to those of other Bothrops sp.…”

Understanding the Bothrops Moojeni Venom: A Justified Challenge

“…In Latin America, snakes of the Bothrops genus are the main responsible for snakebites in humans, causing inflammatory and hemostatic alterations whose pathophysiology is a neglected issue in the toxinology field. 1 In this issue of the International Journal of Cardiovascular Sciences, Natália Barreira Silva et al present a systematic review conducted according to the PRISMA protocol using the terms "Bothrops" and "hemostasis" of scientific articles published in the last 20 years. 2 The authors describe 23 proteins isolated from Bothrops moojeni (B. moojeni) venom that affect hemostasis and their pharmacological and clinical potential.…”

“…Inflammatory responses and coagulation disorders are considered hallmark mechanisms of local and systemic effects of Bothrops snakebites. 1 Crosstalk is responsible for potentiating both inflammatory and hemostatic alterations and enhancing prothrombotic conditions associated with thrombotic microangiopathy. Tissue ischemia is a recent issue in toxinology.…”