Life Science Journal 2013;10(4) http://www.lifesciencesite.com 1534 Hepatoprotective Role of the Pomegranate (Punica Granatum) Juice on Carbon Tetrachloride-Induced Oxidative Stress in Rats Hany M. Yehia 1 , Ebtesam M. Al- Olayan 2 , Manal F. Elkhadragy 2 1 Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, P.O. Box 2460, Riyadh, 11451, Kingdom of Saudi Arabia 2 Chair Vaccines for Infectious Diseases, Women Student Medical Studies & Sciences Sections King Saud University - Building NO: 1 - Kingdom of Saudi Arabia hanyehia@ksu.edu.sa , hanyyehuia43@yahoo.de Abstract: In the present study, the possible protective role of pomegranate (Punica granatum) on the free radical damage of liver caused by carbon tetrachloride in rats was investigated. Treatment of rats with carbon tetrachloride (2 ml/kg, intraperitoneally) produced severe liver injury, as demonstrated by dramatic elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT) and Total bilirubin (TB) levels and typical histopathological changes including hepatocyte necrosis and apoptosis. In addition, carbon tetrachloride (CCl 4 ) administration caused oxidative stress in rats, as evidenced by increased malondialdehyde (MDA) and Nitrite/nitrate (NO) concentrations in the serum and liver of rats, along with a remarkable reduction in hepatic catalase (CAT), superoxide dismutase (SOD), glutathione transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx ) activities and GSH content. However, simultaneous oral treatment with P. granatum significantly attenuated carbon tetrachloride-induced hepatotoxicity. It ameliorated most biochemical markers tested as well as histopathological, apoptosis and necrosis features. It is therefore suggested that P. granatum can provide a definite protective effect against chronic hepatic injury caused by CCl 4 in rats, which may mainly be associated with its antioxidative effect. [Hany M. Yehia, Ebtesam M. Al- Olayan , Manal F. Elkhadragy. Hepatoprotective Role of the Pomegranate (Punica Granatum) Juice on Carbon Tetrachloride-Induced Oxidative Stress in Rats. Life Sci J 2013; 10(4): 1534-1544]. (ISSN: 1097-8135). http://www.lifesciencesite.com . 202 Keywords: Carbon tetrachloride; Punica granatum; oxidative stress; liver. 1.Introduction The liver is a vital organ that plays a key role in many toxication cases (Karakus et al., 2010 ), and various pathological factors such as fatty livers, hepatic virus and chemical hepatotoxins induced liver injury (Xie et al., 2010). Carbon tetrachloride (CCl 4 ) is a well established hepatotoxin. Previous studies showed that both liver and kidneys are the target organs of CCl 4 . Extensive evidence demonstrates that CCl 4 is activated in the liver to highly reactive trichloromethyl radical which initiates free radical- mediated lipid peroxidation of the cytoplasmic membrane phospholipids and causes functional and morphological changes in the cell membrane, which leading to accumulation of lipid-derived oxidants causing liver injury (Singh, 2008). CCl 4 -induced damage is also able to alter the antioxidant status of the tissues, which is manifested by abnormal histopathological changes ( Rajesh and Latha, 2004). Which trichloromethyl radical can react with sulfhydryl groups of glutathione (GSH) and protein thiols. In addition, CCl4 also alters the antioxidant profile of the liver including the antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione transferase (GST) (Srivastava, Shivanandapp, 2006). Histopathologically, exposure to CCl 4 can results in hepatic steatosis, centrilobular necrosis, and cirrhosis in the liver (Xu et al., 2010). There is an intimate relationship between nutrition and the antioxidant defense system, as some exogenous low molecular weight antioxidants may be supplied by the diet. These two main systems of the antioxidant defense act in coordination, their levels being regulated by each other, to avoid oxidative stress events (Masella et al., 2005). In the past few years, a considerably large group of molecules widespread in plants has come into focus. Pomegranate (Punica granatum) is one of the oldest edible fruit and belongs to the Punicacea family (Fadavi et al., 2006). Pomegranate is extensively cultivated in the Mediterranean area and most Near- and Far East countries. This botanic isolation is coincident with a unique biochemistry, the seeds contain an oil of which about 80% is a rare trans 18 carbon fatty acid (punicic acid) (Schubert et al., 1999), and possess the highest botanical concentration of a sex steroid, estrone, at 17mg/kg dried seed (Kim et al., 2002). Pharmacological properties of pomegranate extracts have been scrutinized, with anti-microbial, anti-parasitic, anti-viral, and anti-cancer effects noted (Kim et al., 2002). The fermented juice is potently