Abstract

Purpose: Gut permeability and microvascular injury following ischaemia/reperfusion (IR) have been implicated in the systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF). Taurine (TAU), a sulfur-containing amino acid, is a powerful antioxidant and regulator of intracellular calcium and several studies have established that treatment with TAU protects cerebral, cardiac and testicular tissue from (IR) injury. This study investigates the protective effect of taurine in an experimental model of I/R-induced gut injury in rats. Methods: Sprague-Dawley rats were randomized into three groups: Control, I/R, TAU + I/R. TAU was given by gavage or intravenous injection before I/R. Ischaemia was induced by cross-clamping superior mesenteric and coeliac vascular pedicle for 20 - 30 min, followed by 60 - 180 min reperfusion. Gut permeability, blood flux, tissue oedema, leucocytes infiltration and eNOS expression were measured at 3 hrs following reperfusion using FD4. Leukocyte-endothelial interactions were determined by intra-vital microscopy during I/R. In vitro studies assessed the protective effect of TAU on endothelial cell function and survival. Results: Treatment with TAU significantly attenuated IR-induced gut hyper permeability, tissue oedema, leukocyte adhesion and infiltration. TAU also prevented the reduction in gut blood flow, leukocyte rolling velocity and eNOS expression induced by IR. TAU protects against I/R-induced endothelial cell injury by reduced anti-oxidant activity and modulation of eNOS expression and intracellular calcium fluxes. Conclusions: TAU protects the gut from intestinal barrier dysfunction induced by surgical I/R.

Highlights

  • Interruption or reduction of blood and oxygen supply to tissue results in cellular dysfunction and death leading to organ failure

  • This study investigates the protective effect of taurine in an experimental model of ischeamia and min reperfusion (I/R)-induced gut injury in rats

  • TAU prevented the reduction in gut blood flow, leukocyte rolling velocity and endothelial NOS (eNOS) expression induced by IR

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Summary

Introduction

Interruption or reduction of blood and oxygen supply to tissue results in cellular dysfunction and death leading to organ failure. Reperfusion may paradoxically induce further cell death [1] and injury in distant organs [2] [3]. Reperfusion of ischemic tissue activates immune cells which produce reactive oxygen species (ROS) and nitrogen species (RNS) in excess, and may induce the systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS), and multiple organ dysfunction (MODs) [7]. Intestinal I/R injury is a common clinical occurrence in surgery, haemorrhage, trauma, and sepsis, which results in intestinal barrier dysfunction with pronounced mucosal permeability allowing bacterial translocation and the activation of sub-mucosal cells. The passage of indigenous microorganisms from the intestinal lumen to extra-intestinal sterile sites, plays a significant role for patient undergoing emergency surgery and or who received preoperative total parenteral nutrition (TPN) [10]

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