Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Av. Marechal Campos 1468, Maruípe, 29043-900 Vitória/ES, Brazil.
Toxicon. 2012 Jul;60(1):4-11. doi: 10.1016/j.toxicon.2012.03.008. Epub 2012 Mar 20.
The Scorpaena plumieri fish venom induces a severe pain and edema, observed both clinically and experimentally. In order to understand more about the envenomation syndrome, the present study characterized experimentally the local acute inflammatory response induced by S. plumieri venom (SpV) in a mouse model of tissue injury. Our results demonstrated that the local inflammatory response provoked after 2 h of SpV injection in footpad of mice is characterized by release of pivotal pro-inflammatory mediators (TNF, IL-6 and MCP-1). These mediators could be associated with histopathological changes observed into paw tissue, characterized by cellular infiltration, mainly neutrophils. Additionally, an investigation of edema formation pathways involved in inflammatory response was performed. SpV-induced edema was reduced significantly by previous administration of aprotinin or icatibant (HOE-140). However, the pre-treatment with diclofenac sodium and promethazine had less effect on this response. These results demonstrate that the kallikrein-kinin system (KKS) plays a major role in the edema formation. Despite the whole venom hydrolyzed the kallikrein synthetic substrate S-2302 (Pro-Phe-Arg-pNA), its main pro-inflammatory fraction was devoid of kininogenase activity. Our results demonstrate that SpV evokes a complex inflammatory reaction stimulating a secretion of TNF, IL-6, MCP-1 and leukocytes recruitment at the site of venom injection. In addition provide clear evidence of the involvement of the KKS in inflammatory response induced by S. plumieri venom.
尖吻鲉毒液会引起严重的疼痛和水肿,无论是在临床上还是在实验中都有观察到。为了更深入地了解中毒症状,本研究在组织损伤的小鼠模型中对尖吻鲉毒液(SpV)引起的局部急性炎症反应进行了实验表征。我们的结果表明,SpV 注射到小鼠足底 2 小时后引起的局部炎症反应的特征是释放关键的促炎介质(TNF、IL-6 和 MCP-1)。这些介质可能与爪组织中观察到的组织病理学变化有关,其特征是细胞浸润,主要是中性粒细胞。此外,还对参与炎症反应的水肿形成途径进行了研究。预先给予抑肽酶或 HOE-140(icatibant)可显著减少 SpV 诱导的水肿。然而,预先给予双氯芬酸钠和苯海拉明对这种反应的影响较小。这些结果表明激肽释放酶-激肽系统(KKS)在水肿形成中起主要作用。尽管整个毒液水解了激肽合成底物 S-2302(Pro-Phe-Arg-pNA),但其主要的促炎部分缺乏激肽原酶活性。我们的结果表明,SpV 引发了一种复杂的炎症反应,刺激 TNF、IL-6、MCP-1 的分泌,并在毒液注射部位招募白细胞。此外,还为 S. plumieri 毒液引起的炎症反应中 KKS 的参与提供了明确的证据。