Propofol Attenuates Small Intestinal Ischemia Reperfusion Injury through Inhibiting NADPH Oxidase Mediated Mast Cell Activation.

Xiaoliang Gan,Haobo Li,Zhengyuan Xia,Michael G Irwin,Dandan Xing,Ziqing Hei,Guangjie Su,Shun Li,Chenfang Luo

doi:10.1155/2015/167014

Abstract

Both oxidative stress and mast cell (MC) degranulation participate in the process of small intestinal ischemia reperfusion (IIR) injury, and oxidative stress induces MC degranulation. Propofol, an anesthetic with antioxidant property, can attenuate IIR injury. We postulated that propofol can protect against IIR injury by inhibiting oxidative stress subsequent from NADPH oxidase mediated MC activation. Cultured RBL-2H3 cells were pretreated with antioxidant N-acetylcysteine (NAC) or propofol and subjected to hydrogen peroxide (H2O2) stimulation without or with MC degranulator compound 48/80 (CP). H2O2 significantly increased cells degranulation, which was abolished by NAC or propofol. MC degranulation by CP further aggravated H2O2 induced cell degranulation of small intestinal epithelial cell, IEC-6 cells, stimulated by tryptase. Rats subjected to IIR showed significant increases in cellular injury and elevations of NADPH oxidase subunits p47phox and gp91phox protein expression, increases of the specific lipid peroxidation product 15-F2t-Isoprostane and interleukin-6, and reductions in superoxide dismutase activity with concomitant enhancements in tryptase and β-hexosaminidase. MC degranulation by CP further aggravated IIR injury. And all these changes were attenuated by NAC or propofol pretreatment, which also abrogated CP-mediated exacerbation of IIR injury. It is concluded that pretreatment of propofol confers protection against IIR injury by suppressing NADPH oxidase mediated MC activation.

Highlights

Small intestinal ischemia reperfusion (IIR) injury has been emerged in many pathophysiological settings, including septic and hemorrhagic shock induced hypoperfusion [1], as well as acute mesenteric ischemia [2] and small intestine transplantation or liver resection [3]
Pretreatment with propofol, but not intralipid, abrogated the enhancements of the released βhexosaminidase activities induced by H2O2 (Figure 1(e)), indicating that oxidative stress contributes to mast cell (MC) degranulation and propofol inhibits MC degranulation via its antioxidant property
Despite the fact that MC may function as host defense to prevent bacterial invasion [43], enhanced MC activation may contribute to the development of a variety of disorders including IIR injury by releasing histamine, tryptase, TNF-α, and other factors

Summary

Introduction

Small intestinal ischemia reperfusion (IIR) injury has been emerged in many pathophysiological settings, including septic and hemorrhagic shock induced hypoperfusion [1], as well as acute mesenteric ischemia [2] and small intestine transplantation or liver resection [3]. During IIR, oxidative stress is increased due to burst production of reactive oxygen species (ROS), which is a major mechanism of IIR injury [5]. Numerous studies have revealed that increased ROS production resulted from overactivation of the prooxidant enzyme NADPH oxidase, which abundantly exists in intestine tissue [6] and plays critical roles in mediating tissue injury related to a range of inflammatory diseases [7], including ischemia reperfusion injury [8, 9]. Inhibition of NADPH oxidase by N-acetylcysteine (NAC), a scavenger of oxygen radicals, has been shown to greatly attenuate myocardial ischemia reperfusion injury [10, 11]. The mechanism governing ROS production, from overactivation of NADPH oxidase, during IIR is yet to be explored

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Conclusion