%0 Journal Article
%T Protective Effects of Peroxisome Proliferator-Activated Receptor-¦Á Agonist, Wy14643, on Hypoxia/Reoxygenation Injury in Primary Rat Hepatocytes
%A Ke Chen
%A Yuan-Hai Li
%A Si-Qi Xu
%A Sheng-Hong Hu
%A Lei Zhang
%J PPAR Research
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/547980
%X This study investigates the effects and possible mechanism of an agonist of PPAR¦Á, Wy14643, on primary hepatocytes subjected to H/R injury in rats. H/R induced a significant increase ALT, AST, MDA in the culture medium and ROS in the hepatocytes. These effects were reversed by pretreatment with Wy14643 in the dose-dependent manner. The activity of SOD and the level of GSH in the hepatocytes were decreased after H/R, which were increased by Wy14643 pretreatment. Moreover, the mRNA expressions of PPAR¦Á significantly increased in H/R+Wy14643 groups when compared with that in H/R group. A PPAR¦Á agonist, Wy14643, exerts significant protective effect against H/R injury in primary hepatocytes via PPAR¦Á activation and attenuating oxidative stress. 1. Introduction Ischemia/reperfusion (I/R) injury is a serious complication precipitated during short-term expansion of the invading parasitic pathogens, such as by Entamoeba histolytica as the infections lead to local tissue damage and hypoxia [1]. The condition has also been reported to occur in certain intracellular bacterial infections, for example, Chlamydia species. Mechanisms of I/R injury involve complex and multiple pathways, including the direct ischemic cellular damage as well as the cell injury due to the activation of inflammatory response after reperfusion [2]. A hepatic, in vitro hypoxia/reoxygenation (H/R) model can be use to study the pathophysiology of this injury [3]. Previous study showed that the generation of reactive oxygen species (ROS) is likely to be an important factor in H/R-induced cell damage. Thus, ROS are generated immediately after H/R and activate proapoptotic/inflammatory signalling in the cell or directly damage cell organelles. These include direct oxidation of cellular components and lipids (lipid peroxidation), activation of inflammatory gene transcription, and possible activation of the innate immune response [2, 3]. Administration of antioxidants such as glutathione could afford protection against I/R injury [4, 5]. Oxygen deprivation (hypoxia) during ischemia and subsequent reoxygenation upon reperfusion are thought to be the major factors contributing to ROS production and the subsequent cellular damage [6]. Hypoxia increases mitochondrial reactive oxygen species (ROS) generation at Complex III, and the predominant source of ROS by oxygen limitation originates from mitochondria [7]. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor related to retinoid, steroid, and thyroid hormone receptors. Peroxisome proliferator-activated receptor-¦Á
%U http://www.hindawi.com/journals/ppar/2012/547980/