NDLI: BURN-INDUCED GUT BARRIER INJURY IS ATTENUATED BY PHOSPHODIESTERASE INHIBITION: EFFECTS ON TIGHT JUNCTION STRUCTURAL PROTEINS

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BURN-INDUCED GUT BARRIER INJURY IS ATTENUATED BY PHOSPHODIESTERASE INHIBITION: EFFECTS ON TIGHT JUNCTION STRUCTURAL PROTEINS

Content Provider	PubMed Central
Author	Costantini, Todd W. Loomis, William H. Putnam, James G. Dana, Drusinsky Jessica, Deree Choi, Sunghyuk Wolf, Paul Baird, Andrew Brian, Eliceiri Bansal, Vishal Coimbra, Raul
Copyright Year	2009
Abstract	Loss of intestinal barrier function after burn injury allows movement of intraluminal contents across the mucosa, which can lead to the development of distant organ injury and multiple organ failure. Tight junction function is highly regulated by membrane-associated proteins including occludin and zonula occludens protein 1 (ZO-1), which can be modulated by systemic inflammation. We hypothesized that (1) burn injury leads to gut barrier injury, and (2) phosphodiesterase inhibition will attenuate these burn-induced changes. Male balb/c mice undergoing a 30% steam burn were randomized to resuscitation with normal saline or normal saline + pentoxifylline (PTX; 12.5 mg/kg). Intestinal injury was assessed by histological diagnosis and TNF-α levels using enzyme-linked immunosorbent assay. Intestinal permeability was assessed by measuring the plasma concentration of fluorescein isothiocyanate–dextran after intraluminal injection in the distal ileum. Occludin and ZO-1 levels were analyzed by immunoblotting and immunohistochemistry. Thirty percent total body surface area (TBSA) burn results in a significant increase in intestinal permeability. Treatment with PTX after burn attenuates intestinal permeability to sham levels. Burn injury resulted in a marked decrease in the levels of tight junction proteins occludin and ZO-1 at 6 and 24 h. The use of PTX after burn significantly decreases the breakdown of occludin and ZO-1. Pentoxifylline also attenuates the burn-induced increase in plasma and intestinal TNF-α. Confocal microscopy demonstrates that PTX attenuates the burn-induced reorganization of occludin and ZO-1 away from the tight junction. Pentoxifylline attenuates burn-induced intestinal permeability and decreases the breakdown and reorganization of intestinal occludin and ZO-1. Therefore, phosphodiesterase inhibition may be a useful adjunct strategy in the attenuation of burn-induced gut barrier injury.
Related Links	http://dx.doi.org/10.1097/shk.0b013e3181863080
Ending Page	422
Page Count	7
Starting Page	416
File Format	PDF
ISSN	10732322
e-ISSN	15400514
Journal	Shock (Augusta, Ga.)
Issue Number	4
Volume Number	31
Language	English
Publisher Date	2009-04-01
Access Restriction	Open
Subject Keyword	Critical Care and Intensive Care Medicine Emergency Medicine Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Emergency Medicine Critical Care and Intensive Care Medicine

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