Prophylaxis with ketotifen in rats with portal hypertension:involvement of mast cell and eicosanoids  

作　　者：Fernando Sánchez-Patán Raquel Anchuelo Elena Vara Cruz García Yolanoa Saavedra Patri Vergara Carmen Cuellar Marta Rodero Maria-Angeles Aller Jaime Arias 

机构地区：[1]Department of Surgery I,School of Medicine, Complutense University of Madrid,Spain [2]Department of Biochemistry and Molecular Biology,School of Medicine, Complutense University of Madrid,Spain [3]Department of Physiology,Autonoma University of Barcelona,Spain [4]Department of Parasithology,School of Pharmacy,Complutense University of Madrid,Spain

出　　处：《Hepatobiliary & Pancreatic Diseases International》2008年第4期383-394,共12页国际肝胆胰疾病杂志（英文版）

基　　金：grants from the Department of Health.Castilla-La Mancha Regional Council(Ref.04047-00 and PI-2007/64).Ketotifen was kindly provided by Novartis(Barcelona,Spain).

摘　　要：BACKGROUND:Since we have previously shown an increase of mast cells in the small bowel and in the mesenteric lymph nodes in the rats with prehepatic portal hypertension,it can be hypothesized that this essential inflammatory cell would be involved in the pathogeny of the splanchnic changes related to portal hypertension. METHODS:To verify this hypothesis,we first studied mast cell infiltration in the ileum and in the mesenteric lymph nodes in sham-operated male Wistar rats(n=12) and in short-term prehepatic portal hypertensive rats (n=12),and the serum levels of rat mast cell protease Ⅱ(RMCP-Ⅱ)by ELISA.In a second set of experiments ketotifen,a mast cell stabilizer drug,was administered to sham-operated(n=10)and portal hypertensive(n=12) rats 24 hours before the intervention and prostanoids (PGE2,PGI2,TXB2)and leukotrienes(LTC4,LTB4)were assayed by RIA,mast cell infiltration in the ileum and in the mesenteric lymph nodes and the serum levels of RMCP-Ⅱwere also studied,to show its effectiveness to prevent the mesenteric alterations produced by the inflammatory mediators released by the mast cell. RESULTS:Forty-eight hours after the intervention RMCP-Ⅱ (P<0.05),PGE2(P<0.001)and LTC4 serum levels decreased and mast cell number and RMCP-Ⅱlevels increased in mesenteric lymph nodes in portal hypertensive rats.Prophylactic administration of ketotifen reduced portal pressure(P<0.001),serum levels of PGE2(P<0.001)and RMCP-Ⅱ(P<0.001)in mesenteric lymph nodes. CONCLUSIONS:In acute portal hypertension in the rat,the mast cell translocation from intestinal mucosa to mesenteric lymph nodes,where they are activated and degranulates,would represent a defence mechanism to avoid the activation of an acute and massive inflammatory response in this location.Prophylactic administration of ketotifen is able to reduce the splanchnic inflammatory changes related to acute portal hypertension in the rat.BACKGROUND:Since we have previously shown an increase of mast cells in the small bowel and in the mesenteric lymph nodes in the rats with prehepatic portal hypertension,it can be hypothesized that this essential inflammatory cell would be involved in the pathogeny of the splanchnic changes related to portal hypertension. METHODS:To verify this hypothesis,we first studied mast cell infiltration in the ileum and in the mesenteric lymph nodes in sham-operated male Wistar rats(n=12) and in short-term prehepatic portal hypertensive rats (n=12),and the serum levels of rat mast cell protease Ⅱ(RMCP-Ⅱ)by ELISA.In a second set of experiments ketotifen,a mast cell stabilizer drug,was administered to sham-operated(n=10)and portal hypertensive(n=12) rats 24 hours before the intervention and prostanoids (PGE2,PGI2,TXB2)and leukotrienes(LTC4,LTB4)were assayed by RIA,mast cell infiltration in the ileum and in the mesenteric lymph nodes and the serum levels of RMCP-Ⅱwere also studied,to show its effectiveness to prevent the mesenteric alterations produced by the inflammatory mediators released by the mast cell. RESULTS:Forty-eight hours after the intervention RMCP-Ⅱ (P<0.05),PGE2(P<0.001)and LTC4 serum levels decreased and mast cell number and RMCP-Ⅱlevels increased in mesenteric lymph nodes in portal hypertensive rats.Prophylactic administration of ketotifen reduced portal pressure(P<0.001),serum levels of PGE2(P<0.001)and RMCP-Ⅱ(P<0.001)in mesenteric lymph nodes. CONCLUSIONS:In acute portal hypertension in the rat,the mast cell translocation from intestinal mucosa to mesenteric lymph nodes,where they are activated and degranulates,would represent a defence mechanism to avoid the activation of an acute and massive inflammatory response in this location.Prophylactic administration of ketotifen is able to reduce the splanchnic inflammatory changes related to acute portal hypertension in the rat.

关 键 词：portal hypertension PROSTAGLANDINS LEUKOTRIENES mast cell 

分 类 号：R575.2[医药卫生—消化系统]