Contribution of mast cells and snake venom metalloproteinases to the hyperalgesia induced by Bothrops jararaca venom in rats.
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.
Bonavita
André Gustavo C
AG
Laboratory of Inflammation, Department of Physiology and Pharmacodynamics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Av. Brasil, CEP 21040-900, 4365 Rio de Janeiro, Brazil.
da Costa
Aline S
AS
Pires
Ana Lucia A
AL
Neves-Ferreira
Ana G C
AG
Perales
Jonas
J
Cordeiro
Renato S B
RS
Martins
Marco A
MA
e Silva
Patrícia M R
PM
D000818:Animals; D017837:Bothrops; D003435:Crotalid Venoms / Q000633:toxicity*; D005260:Female; D006930:Hyperalgesia / Q000139:chemically induced*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology*; D045726:Metalloproteases / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D003435:Crotalid Venoms; D045726:Metalloproteases