mdl-100907 and Edema

Major thermal injuries lead to a systemic inflammatory response with systemic capillary leakage and multiple organ dysfunction. This systemic inflammatory response is induced by a variety of immunmodulative molecules including TNFα and serotonin. Unspecific serotonin antagonism leads to reduced macromolecular efflux in rat mesenteries after burn plasma transfer. The aim of the present study was to evaluate the effect of specific 5-HT2a antagonism on early burn edema.. Donor rats (DR) underwent thermal injury (100 °C water, 30% BSA, 12 s) for positive controls. For negative controls, DR underwent sham burn (37 °C water, 30% BSA, 12 s). DR plasma (harvested 4 h post-trauma) was transferred to healthy individuals for positive controls. Study rats received burn plasma (BP) and a Bolus injection of Ketanserin (Ket) (1 mg kg(-1) body weight). Negative controls underwent sham burn plasma infusion. Intravital microscopy was performed in mesenteric venules (0/60/120 min). Edema was assessed by FITC-albumin extravasation. Additionally, leukocyte rolling and sticking (cells mm(-2)) as well as microhemodynamic parameters were assessed.. Significant systemic capillary leakage was observed after BP transfer at 120 min and additional administration of Ket attenuated the postburn edema to sham burn levels. Ket also leads to significantly decreased leukocyte-endothelial interactions when compared to positive controls.. 5-HT2a antagonism reduces plasma extravasation after burn plasma transfer in healthy individuals. The influence of leukocyte-endothelial interactions on postburn edema remains unclear.

Topics: Animals; Burns; Edema; Endothelium, Vascular; Hemodynamics; Ketanserin; Leukocytes; Mesentery; Rats, Wistar; Receptor, Serotonin, 5-HT2A; Serotonin 5-HT2 Receptor Antagonists; Serum Albumin

The anti-inflammatory activity of quercetin was evaluated through serotonin-induced rat-paw edema. The experiments showed that quercetin had an important effect on acute inflammatory processes. Docking of serotonin and quercetin into the homology model of the 5-Hydroxytryptamine Type 2 Receptor allowed to analyze the structural basis of the anti-inflammatory activity. Results showed that serotonin and quercetin bind in the same region of the active site with a similar binding energy but quercetin has a much bigger inhibition constant. Therefore, it seems possible that quercetin may act as a natural inhibitor of the receptor blocking the acute inflammation generated by serotonin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Binding Sites; Edema; Models, Molecular; Protein Conformation; Quercetin; Rats; Rats, Wistar; Receptors, Serotonin, 5-HT2; Serotonin; Serotonin 5-HT2 Receptor Antagonists