Contribution of mast cells and snake venom metalloproteinases to the hyperalgesia induced by Bothrops jararaca venom in rats.

Laboratory of Inflammation, Department of Physiology and Pharmacodynamics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Av. Brasil, CEP 21040-900, 4365 Rio de Janeiro, Brazil.
Toxicon (Impact Factor: 2.58). 07/2006; 47(8):885-93. DOI: 10.1016/j.toxicon.2006.02.017
Source: PubMed

ABSTRACT Bothrops jararaca venom (Bjv) is known to induce local inflammation and severe pain. Since, mast cells are able to secrete mediators involved in algesic processes, in this study we examined the putative role of these cells in the hyperalgesia triggered by Bjv in the rat paw. We noted that treatment with mast cell stabilizer sodium cromoglicate as well as with histamine and 5-hydroxytriptamine receptor antagonists meclizine and methysergide, respectively, inhibited the Bjv-induced hyperalgesia. In addition, we showed that stimulation of isolated rat peritoneal mast cells with Bjv in vitro resulted in the release of stored and neo-generated inflammatory mediators such as histamine and leukotriene C(4), respectively. Bjv-induced histamine secretion was clearly sensitive to treatment with sodium cromoglicate and sodium nedocromil. We further observed that metalloproteinase inhibitors 1,10-phenantroline and DM43 inhibited mast cell degranulation in vitro, under conditions where inhibitors of phospholipase A(2) as well as of serine- and cysteine-proteinases were inactive. Altogether, our findings indicate that mast cells seem to contribute to the hyperalgesia caused by Bjv in the rat paw, and also provide evidence that this response might be dependent on the ability of the Bjv to activate directly mast cells.

Download full-text


Available from: Andre Bonavita, Mar 14, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Various toxins isolated from Bothrops snake venoms induce inflammatory reactions and have been claimed to contribute to the severity of local symptoms present in this envenomation. Notwithstanding, the relative participation of serine proteases, metalloproteases and phospholipases A(2) in the inflammatory reaction produced by crude Bothrops venoms is poorly understood. Herein, crude Bothrops jararaca venom was treated with phenylmethanesulfonyl fluoride (PMSF), 1,10-phenanthroline (oPhe), or p-bromophenacyl-bromide (p-BPB) to inhibit those classes of enzymes, respectively, and inflammatory parameters were evaluated and compared to those induced by the control crude venom. The intensity of edema and hyperalgesia/allodynia was remarkably reduced in animals administered with oPhe-treated venom. Leukocyte-endothelium interactions (LEI), such as adhesion and migration of leukocytes, were also modified at 2h and 24h. Edema and LEI parameters induced by p-BPB-treated venom were similar to those observed with the control venom, but hyperalgesia/allodynia was significantly lower. Inflammatory parameters induced by PMSF-treated venom were similar to those induced by the crude venom, except for a mild reduction in edema intensity. Our results indicate that metalloproteases have a pivotal role in the inflammatory reactions induced by B. jararaca venom, and phospholipases A(2) and serine proteases have a minor role.
    Toxicon 08/2009; 55(2-3):227-34. DOI:10.1016/j.toxicon.2009.07.025 · 2.58 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    Toxicon 09/2009; 55(2-3):343-52. DOI:10.1016/j.toxicon.2009.08.009 · 2.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To provide a review and update on the medical management of pit viper envenomation in dogs. Pit viper snake (Crotalidae) envenomation in dogs is a common emergency in the United States. At least 50 enzymes contribute to snake venom potency that causes soft tissue damage, vasculotoxicity, coagulopathy, cytotoxicity, and necrosis. Snakebite envenomation may be identified by fang puncture wounds but primarily as a focal site with a rapid onset of severe swelling, hemorrhage, pain, and potentially necrosis. Crotalid venom causes hematologic abnormalities, local tissue damage, hypotension, and occasionally neurological impairment. The most marked hematologic abnormalities include thrombocytopenia, hemolytic anemia, and various forms of coagulopathy, including defibrination without disseminated intravascular coagulation (in North America), summarized as a venom-induced coagulopathy. The mainstay of treatment includes intravenous crystalloid fluid therapy, antivenom, and analgesic medications. Currently available antivenom products include a mixed polyvalent Antivenin (Crotalidae) Polyvalent (ACP(a)), and Crotalinae polyvalent immune Fab (Crofab(b)). There are products from Mexico and Costa Rica that have limited availability, a similar imported Fab product (Antivipmyn(c)), and a polyspecific antivenom (Polyvet-ICP(d)), respectively. Glucocorticoids, nonsteroidal antiinflammatory drugs (NSAIDs) and antihistamines are not included in the majority of recommended treatment protocols by world authorities; however, there are some reports that describe their use. Antimicrobial therapy and blood products are used only when clinically indicated. There is a vaccine available, but at present, it is of unknown efficacy because of a lack of documented scientific information. Mortality from North American crotalid envenomation is generally rare and is influenced by several variables, including the amount of venom injected, the size and species of snake, the size of the victim, the location of the bite, time elapsed until treatment, and the therapy initiated. Mortality rates range from 1% to 30%.
    10/2011; 21(5):461-70. DOI:10.1111/j.1476-4431.2011.00677.x