Accion del lipopolisacarido de escherichia coli sobre la absorcion de d- galactosa a traves de yeyuno de conejo

Abstract

the action of scherichia coli lipopolysacchart.DE IN DE absortion of D-galactose across rabbit JEJUNE Ma del Pilar Amador Rodríguez, Faculty of Farmacy, University of Navarra (Spain) 2006. The aim of this work was to study the LPS and TNF-a effect on intestinal absorption of D-galactose in rabbit. Moreover, we proposed to investígate the possible mechanisms implicated in this action and characterize the effect on SGTl D-galactose transporter. we assayed two work protocols: the tissue exposed directly to LPS (local effect) and intravenous administrat!on of LPS or TNF-a (systemic effect). Rabbit jejunum was used as the experimental model because it is the part of the small intestine with the highest levéis of absorption. When LPS was added directly to tissue there was a partial reduction of D-galactose transport located on the mucosa! si de. The endotoxin did not modify D-galactose diffusión across the intestinal epithelium. However, the Na+-dependent transport system was affected by LPS with a diminution of the transporter affinity. In addition, we found a reduction of the Na+/ K+-ATPase activity. In the LPS inhibitory effect on D-galactose intestinal transport, intracellular processes related to PKC, Ca2+-calmòdul in and MAPKs (p38 MAPK, JNK, MEKl/2) could be implicated. On the other hand, intravenous LPS administration inhibited D-galactose absorption by reducing the number of SGLTl transporters, with the possible implication of pkc, pka, mapks (p38 mapk, JNK, MEKl/2) and proteasome. Simi 1 ariy, the secretagoge action of this endotoxin on the gut mediated by cytokines as TNF-a could have contributed to this effect. On the other hand, we found that LPS increase signi fi canti y the mRNA-SGLTl levéis which could be related to mRNA stability. The intravenous administration of TNF-a also produced an inhibition on D-galactose mucosal intestinal transport. This action could be produced by a reduction in the number of SGLTl transporters. The PKA, PKC, MAPKs and proteasome ways could be implicated. Likewise, TNF-a increased significantly the mRNA-SGLTl level.