Research Article Association between Paraoxonases Gene Expression and Oxidative Stress in Hepatotoxicity Induced by CCl 4 Mohamed M. Hafez, 1 Othman A. Al-Shabanah, 1 Naif O. Al-Harbi, 1 Mohamed M. Al-Harbi, 1 Salim S. Al-Rejaie, 1 Saad M. Alsurayea, 2 and Mohamed M. Sayed-Ahmed 1 1 Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia 2 Riyadh Regional Laboratory and Blood Bank, Riyadh 11451, Saudi Arabia Correspondence should be addressed to Mohamed M. Hafez; mohhafez 2000@yahoo.com Received 13 June 2014; Revised 22 August 2014; Accepted 22 August 2014; Published 17 November 2014 Academic Editor: Liang-Jun Yan Copyright © 2014 Mohamed M. Hafez et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives. Te purpose of the study is to evaluate the hepatoprotective efect of rutin in carbon tetrachloride- (CCl 4 -) induced liver injuries in rat model. Methods. Forty male Wistar albino rats were divided into four groups. Group I was the control group and received dimethyl sulphoxide (DMSO) and olive oil. Group II received rutin. Groups III was treated with CCl 4 . Group IV was administered rutin afer 48 h of CCl 4 treatment. Liver enzymes level, lipid profle, lipid peroxidation, and hydrogen peroxide were measured. Te genes expression levels were monitored by real time RT-PCR and western blot techniques. Results. CCl 4 group showed signifcant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), thiobarbituric acid reactive substances (TBAR), hydrogen peroxide (H 2 O 2 ), and lipid profle and a signifcant decrease in glutathione peroxidase (GPx), glutathione S transferase (GST), catalase (CAT), paraoxonase-1 (PON-1), paraoxonase-3 (PON-3), peroxisome proliferator activated receptor delta (PPAR-), and ATP-binding cassette transporter 1 (ABAC1) genes expression levels. Interestingly, rutin supplementation completely reversed the biochemical and gene expression levels induced by CCl 4 to control values. Conclusion. CCl 4 administration causes aberration of genes expression levels in oxidative stress pathway resulting in DNA damage and hepatotoxicity. Rutin causes hepatoprotective efect through enhancing the antioxidant genes. 1. Introduction Liver is important in regulating metabolic functions and various physiological processes [1]. In addition, it is involved in detoxifcation of some drugs and xenobiotics which lead to an increase susceptible to the toxicity from these agents [2]. Oxidative stress is correlated with infammation, cancer, and multiple organ toxicity [3]. Exposure to toxic chemicals can cause hepatocyte injuries through metabolic activation of reactive oxygen species (ROS), such as superoxide, hydroxy radicals, and H 2 O 2 [4]. ROS can induce tissue injury via lipid peroxidation and enhance liver fbrosis by increasing collagen synthesis [5, 6]. Antioxidants enzymes act as free radical scavenging systems and provide frst-line defense against ROS such as superoxide dismutase (SOD), CAT, GPx, and nutritional antioxidants [7]. Teir role as protective enzymes is well known and is investigated extensively in in vivo models. CAT and GPx catalyze dismutation of the superoxide anion (O 2− ) to H 2 O 2 and then to water thus providing protection against ROS. Te paraoxonase (PON) gene is a family that contains three members, PON1, PON2, and PON3 [8]. PON1 is synthesized primarily in liver and secreted into plasma and its natural physiological function is metabolism of toxic oxidized lipids of both low density lipoprotein (LDL) and HDL particles [9]. PON3 is predominantly expressed in liver and is associated with HDL. PON1 and PON3 share the lactonase activity and antioxidant property which participate in preventing LDL oxidation [10]. Te enzymatic activities of PON1 and PON3 are diferent [11, 12]. Numerous studies are focused on the relationship between PON1/PON3 and the development of oxidative stress related diseases [13, 14]. PON2 has antioxidant properties and is more widely distributed [10, 15]. Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity Volume 2014, Article ID 893212, 12 pages http://dx.doi.org/10.1155/2014/893212