Contribution of mast cells to the oedema induced by Bothrops moojeni snake venom and a pharmacological assessment of the inflammatory mediators involved

Abstract

The ability of Bothrops moojeni venom (BmV) to induce oedema in mice, the involvement of principal inflammatory mediators and mast cells (MCs) were investigated. The intraplantar injection of BmV (0.3-6 microg/paw) caused a dose- and time-dependent oedema with a peak between 30 and 60 min after venom injection (0.3-1 microg/paw), disappearing within 24h. Either MCs granule inhibition or depletion by cromoglycate or C48/80, respectively, markedly reduced BmV-induced oedema. MCs depletion by imatinib also reduced oedema. Intraperitoneal BmV injection (2.5-10 microg/site) induced MCs degranulation and release of PGD(2). Treatment with promethazine, cimetidine or thioperamide, histamine H1, H2 and H3/H4 receptor antagonists, respectively, markedly reduced the initial phase of oedema. Combined treatment with these antagonists further reduced, but not abrogated oedema. Indomethacin or eterocoxib (cyclooxygenase inhibitors) reduced oedema until 180 min, whereas zileuton (lipoxygenase inhibitor) affected this event until 60 min. Dexamethazone caused a long lasting reduction of oedema. However, L-NAME and aminoguanidine (NO synthase inhibitors) significantly increased BmV-induced oedema. In conclusion, BmV induces oedema, mediated by MCs degranulation, histamine by H1, H2, H3/H4 receptors, prostaglandins and leukotrienes, and down-regulated by NO. Partial neutralization of oedema was observed even when polyspecific bothropic antivenom was injected immediately after venom.

Inflammatory mediators involved in the paw edema and hyperalgesia induced by Batroxase, a metalloproteinase isolated from Bothrops atrox snake venom

“…Dexamethasone is widely effective in experimental models of paw edema induced by snake venoms as B. asper [14], B. jararaca [55], B. moojeni [32], B. insularis [1] and B. lanceolatus [34]. In the present study, the edema and hyperalgesia induced by Batroxase were significantly reduced by this steroidal anti-inflammatory drug.…”

“…present study, pretreatment of animals with MK-886, a FLAP inhibitor, reduced the paw edema only at the first hour after injection of Batroxase, suggesting the involvement of leukotrienes in the initial phase of this response. Leukotrienes were also shown to be important mediators of the edema response induced by B. jararaca [76] and B. moojeni [32] snake venoms.…”

“…The hemorrhage induced by SVMPs is due to the lysis of basement membranes of blood vessels [31], causing tissue lesion that can be followed by acute inflammatory reaction, inducing plasma extravasation and leukocyte infiltration [71] and initiating an inflammatory process where hyperalgesia and edema are evident [32].…”

In vitroandin vivogenotoxic evaluation ofBothrops moojenisnake venom

“…Snake venoms are a complex mixture of compounds responsible for local and systemic responses during envenoming, which is characterized by edema and inflammation (Galvão Nascimento et al, 2010), hemorrhage (De Roodt et al, 2003), hypotension (Silveira et al, 2013), nephrotoxicity (Barbosa et al, 2002), and myotoxicity (Santos-Filho et al, 2008). Despite their harmful effects, snake venoms represent an important source of bioactive molecules, contributing for the development of new therapeutic agents to be used in the treatment of envenomation and diseases such as cancer, thrombosis, and hypertension (Koh et al, 2006).…”

INFLUENCE OF A LOW-LEVEL SEMICONDUCTOR GALLIUM ARSENATE LASER IN EXPERIMENTAL ENVENOMATION INDUCED BY <i>BOTHROPS ATROX</i> SNAKE VENOM

“…At present, adequate treatment of snakebite envenoming, depend on the ability of antivenoms to reverse signs systemic as coaguloapty, hemorrhage, hypontensive shock and others disorders (Calvete et al, 2009), which neutralizes systemic alterations, but does not prevent local effects and resultant disabilities (Nascimento et al, 2010). Other therapeutic alternatives have been proposed to complement the treatment of local effects caused by bothropic venom, such as the use of plant extracts , Science Publications AJPT synthetic drugs and low power laser (Barbosa et al, 2008).…”