Role of Lymphatic System on Snake Venom Absorption

Abstract

For several decades, advances have been made in venom characterization, mechanism of toxicity, and antivenom therapy. Much of this research has been based on models of the blood vascular system, to analyze the pharmacokinetics of venoms and antivenoms. However, in clinical envenomations, venom is injected into the interstitial space and an absorption process is necessary before it reaches the bloodstream. Absorption may occur by way of the blood or lymphatic capillaries, depending on the physicochemical properties of the molecules involved. Until recently, the role of the lymphatics in envenomation remained essentially unexplored, although several reports have demonstrated the fundamental role of the lymphatic system in the absorption of therapeutic proteins, administered subcutaneously. This review describes the absorption process, from the interstitial space and extracellular matrix through the entry into the blood capillaries and early lymphatics. Venom toxins interact with hyaluronic acid in the extracellular matrix, facilitating interstitial spread before entry into the vessels, and they induce local damage to the vascular endothelium, resulting in local hemorrhage and edema and altering the absorption characteristics of damaged vessels. Large molecules are absorbed primarily via the lymphatics, providing them a fundamentally different toxicokinetic profile from that of smaller toxins for which direct access to the blood capillaries is possible. Improved knowledge of the mechanism and factors influencing the subcutaneous venom absorption can improve the understanding of the role of edema, patterns of local injury, the toxicokinetics of envenomation, the effect of pressure immobilization, the pharmacodynamics and dosing of antivenom, and the phenomenon of recurrent venom effect.

Treatment with Vitis vinifera extract for controlling ascites and local swelling in snakebites

“…From the interstitium, toxins diffuse through the extracellular matrix until they reach a vessel with a permeable endothelium, where they can be absorbed [ 3 – 6 , 12 , 13 ]. The permeability of the blood vascular endothelium decreases as toxin molecular size increases.…”

“…The permeability of the blood vascular endothelium decreases as toxin molecular size increases. Large molecules are absorbed primarily through the lymphatics, producing a fundamentally different toxicokinetic profile from that of smaller toxins, which can achieve direct access to the blood capillaries [ 13 ]. Viperid snake venoms are rich in large molecule toxins and possess a pharmacokinetic profile characterized by a rapid initial absorption phase followed by a complex and slow absorption process from the site of venom injection [ 3 – 6 , 12 , 13 ].…”

“…The swelling spreads rapidly from the site of the bite and may involve the entire limb and adjacent trunk owing to the action of hyaluronic acid and metalloproteases [ 11 ]. Regional lymphadenopathy may also develop as a result of the large molecule toxins and can hinder absorption of the retained fluid [ 10 – 13 ]. If the envenomed tissue is contained in a tight fascial compartment, such as the pulp space of the digits or anterior tibial compartment, ischemia will develop [ 10 – 13 ].…”

“…Regional lymphadenopathy may also develop as a result of the large molecule toxins and can hinder absorption of the retained fluid [ 10 – 13 ]. If the envenomed tissue is contained in a tight fascial compartment, such as the pulp space of the digits or anterior tibial compartment, ischemia will develop [ 10 – 13 ].…”

Rastreamento em células in vitro de uma fosfolipase A2 da peçonha de Bothrops alternatus por meio de pontos quânticos de tamanhos mágicos

“…No local da picada, há a presença de necrose, edema, dor, quadros hemorrágicos e de infiltrados inflamatórios (DELAFONTAINE et al, 2017;GUTIÉRREZ et al, 2016;MAMEDE et al, 2016;KURUPPU et al, 2007). A distribuição sistêmica das toxinas é facilitada pelo sistema vascular e linfático, ocasionando alterações cardíacas, cerebrais, pulmonares e até a morte do indivíduo (PANIAGUA et al, 2015;HERRERA et al, 2013).…”