Carbon Monoxide-Releasing Molecule-2 Reduces Intestinal Epithelial Tight-Junction Damage and Mortality in Septic XXXX .

@entity32 @entity295 @entity32243 @entity35 @entity16 @entity1505 @entity659 @entity3426 @entity505
OBJECTIVE: Damage to intestinal epithelial tight junctions plays an important role in @entity295 . Recently we found that @entity505 Monoxide-Releasing Molecule-2 (CORM-2) is able to protect LPS-induced intestinal epithelial tight junction damage and in this study we will investigate if CORM-2 could protect intestinal epithelial tight junctions in the @entity35 cecal ligation and puncture (CLP) model. MATERIALS AND METHODS: The CLP model was generated using male Sprague-Dawley (SD) @entity35 according to standard procedure and treated with CORM-2 or inactive CORM-2 (iCORM-2), 8 mg/kg, i.v. immediately after CLP induction and euthanized after 24h or 72h (for mortality rate only). Morphological changes were investigated using both transmission electron and confocal microscopy. The levels of important TJ proteins and phosphorylation of myosin light chain (MLC) were examined using Western blotting. Cytokines, @entity3426 and @entity1505 were measured using ELISA kits. The overall intestinal epithelial permeability was evaluated using FD-4 as a marker. RESULTS: CORM-2, but not iCORM-2, significantly reduced @entity295 -induced @entity16 (including TJ disruption), TJ protein reduction (including zonula occludens-l (ZO-1), @entity32243 and @entity659 ), MLC phosphorylation and proinflammatory cytokine release. The overall outcomes showed that CORM-2 suppressed @entity295 -induced intestinal epithelial permeability changes and reduced mortality rate of those septic @entity35 . CONCLUSIONS: Our data strongly suggest that CORM-2 could be a potential therapeutic reagent for @entity295 by suppressing @entity32 , restoring intestinal epithelial barrier and reducing mortality.
