Bonavita André Gustavo C, da Costa Aline S, Pires Ana Lucia A, Neves-Ferreira Ana G C, Perales Jonas, Cordeiro Renato S B, Martins Marco A, e Silva Patrícia M R
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. 2006 Jun 15;47(8):885-93. doi: 10.1016/j.toxicon.2006.02.017. Epub 2006 Mar 24.
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.
众所周知，巴西矛头蝮蛇毒（Bjv）会引发局部炎症和剧痛。由于肥大细胞能够分泌参与痛觉过程的介质，在本研究中，我们探究了这些细胞在Bjv诱发的大鼠爪部痛觉过敏中可能发挥的作用。我们注意到，分别用肥大细胞稳定剂色甘酸钠以及组胺和5-羟色胺受体拮抗剂美克洛嗪和甲基麦角新碱进行治疗，可抑制Bjv诱发的痛觉过敏。此外，我们还表明，在体外，用Bjv刺激分离的大鼠腹膜肥大细胞会分别导致储存的和新生成的炎症介质如组胺和白三烯C4的释放。Bjv诱导的组胺分泌对色甘酸钠和奈多罗米钠的治疗明显敏感。我们进一步观察到，在磷脂酶A2以及丝氨酸和半胱氨酸蛋白酶抑制剂无活性的条件下，金属蛋白酶抑制剂1,10-菲咯啉和DM43在体外可抑制肥大细胞脱颗粒。总之，我们的研究结果表明，肥大细胞似乎参与了Bjv在大鼠爪部引起的痛觉过敏，并且还提供了证据表明这种反应可能依赖于Bjv直接激活肥大细胞的能力。
