First report of interruption of mast cell degranulation and endothelial cells activation by anti-inflammatory drugs controlling the acute response provoked by Pseudoplatystoma fasciatum fish venom

• DOI: 10.1016/j.toxicon.2014.08.007
• Publication Date: 2014-08-21T11:00:31Z
• Authors: Mônica Lopes-Ferr...; Eduardo Martins G...; Fernanda Miriani ...; Marcio Jose Ferreira; Patrícia Charvet; Carla Lima
• Keywords: Inflammation; Male; 0303 health sciences; Anti-Inflammatory Agents; Fishes; Cell Degranulation; 3. Good health; Mice; 03 medical and health sciences; Animals; Marine Toxins; Endothelium; Mast Cells

This is the first report describing in mice the envenoming that possible to occur in humans provoked by Pseudoplatystomafasciatum and evaluated the different class of mediators involved in the inflammatory injury, identifying important targets for drugs intervention. First we demonstrate that P. fasciatum venom induces an acute inflammatory response characterized by the recruitment of immune cells into peripheral tissues choreographed by chemoattractants including lipid mediators (LTB4 and PGE2), cytokines (IL-1β and TNF-α), and chemokines (KC and MCP-1). Intravital microscopy studies showed that only high dose (60 μg) of venom promoted hemodynamic changes inducing an abundant number of thrombi of varying sizes in venules leading to transient venular stasis with reduced blood flow. We found that serotonin, leukotrine and prostaglandin are involved in edematogenic and nociceptive responses, since a selective COX-2 inhibitor, a non-specific inhibitor for cytokines and COX-2, and a non-selective 5-HT receptor antagonist were able to reduce both symptoms. In conclusion, our data show that the main symptoms of acute inflammation as pain provoked by P. fasciatum fish venom could be well managed by available drugs as COX-2 inhibitors as well dexamethasone or non-selective 5-HT receptor antagonists.