Comparative analysis of local effects caused by Bothrops alternatus and Bothrops moojeni snake venoms: enzymatic contributions and inflammatory modulations

Abstract

Bothropic envenomation is characterised by severe local damage caused by the toxic action of venom components and aggravated by induced inflammation. In this comparative study, the local inflammatory effects caused by the venoms of Bothrops alternatus and Bothrops moojeni, two snakes of epidemiological importance in Brazil, were investigated. The toxic action of venom components induced by bothropic venom was also characterised. Herein, the oedema, hyperalgesia and myotoxicity induced by bothropic venom were monitored for various lengths of time after venom injection in experimental animals. The intensity of the local effects caused by B. moojeni venom is considerably more potent than B. alternatus venom. Our results also indicate that metalloproteases and phospholipases A2 have a central role in the local damage induced by bothropic venoms, but serine proteases also contribute to the effects of these venoms. Furthermore, we observed that specific anti-inflammatory drugs were able to considerably reduce the oedema, the pain and the muscle damage caused by both venoms. The inflammatory reaction induced by B. moojeni venom is mediated by eicosanoid action, histamine and nitric oxide, with significant participation of bradykinin on the hyperalgesic and myotoxic effects of this venom. These mediators also participate to inflammation caused by B. alternatus venom. However, the inefficient anti-inflammatory effects of some local modulation suggest that histamine, leukotrienes and nitric oxide have little role in the oedema or myotoxicity caused by B. alternatus venom.

Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis

“…The pain induced by PLA2s is driven by inflammatory processes and sensory neuronal activation. Bradykinin is an important mediator of the inflammatory pain induced by PLA2s (Moreira et al, 2014;Urs et al, 2014;Mamede et al, 2016;Zambelli et al, 2017b). It induces mechanical hyperalgesia dependent on the production of TNF-α, IL-1β, and prostaglandins (Cunha et al, 1992).…”

“…Interestingly, some PLA2s, SVSPs, and SVMPs are also capable of triggering severe pain by modulating pain pathways through activation of ion channels, such as transient receptor potential vanilloid type 1 (TRPV1) and acid-sensing ion channel (ASIC) (Bohlen et al, 2011;Zhang et al, 2017); and/or by pain sensitization through inflammatory mediators (Zychar et al, 2010;Menaldo et al, 2013;Ferraz et al, 2015;Mamede et al, 2016;Zambelli et al, 2017b). The inflammation induced by the elapid and viper venoms is widely reported to produce pain or hyperalgesia in human and in experimental models (Hifumi et al, 2015;Bucaretchi et al, 2016;Kleggetveit et al, 2016;Mamede et al, 2016). Unfortunately, these are not completely reversed by antivenom and anti-inflammatory therapies (Picolo et al, 2002;Ferraz et al, 2015;Hifumi et al, 2015).…”

Edema Induced by a Crotalus durissus terrificus Venom Serine Protease (Cdtsp 2) Involves the PAR Pathway and PKC and PLC Activation

“…Recent studies strongly suggested that serine proteases BpirSP27 and BpirSP41, purified from Bothrops pirajai (Bpir), were able to activate the complement system, potentially inducing edema under experimental conditions, and may include proinflammatory features, as well as being significantly inhibited by nonsteroidal anti-inflammatory drugs [6,7,8]. Other SVSPs purified from Bothrops alternatus , Bothrops mooeni [9], Trimeresurus elegans , and Trimeresurus jerdonni venom revealed the ability to release kinin, as well as fibrinolytic and edematogenic activities [10]. …”

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

“…Os efeitos fisiopatológicos motivados, principalmente, por essas classes de toxinas são divididos em locais e sistêmicos, alterando a homeostasia tecidual e o bom funcionamento dos órgãos. 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).…”

“…A ação das svPLA 2 sobre os tecidos do organismo gera distúrbios fisiopatológicos após o envenenamento ofídico, como efeitos miotóxicos, cardiotóxicos, neurotóxicos e alterações inflamatórias e hemostáticas (MAMEDE et al 2016;BERNARDES et al, 2015;MOREIRA et al, 2014;RODRIGUES et al 2014;TONELLO et al, 2012;RIGONI et al, 2008;MONTECUCCO et al, 2008;.…”