الفهرس 
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Abstract
This study aimed to evaluate the effect of DEN/CCl4-induced hepatotoxicity in obese rats. The experiment was conducted on forty mature male albino rats weighing 150-160 gram. They were divided into four equal groups as follow, In the first group which serve as control group, rats were fed on standard diet, and injected with normal saline, while in second group (DEN/CCl4), hepatotoxicity induced by single I.P. injection of DEN with a dose of 200 mg/kg body weight at 5th week of experiment then followed by subcutaneous injection of CCl4 (3 ml/kg body weight) weekly for six consecutive weeks. In-group three (obese group), obesity induced by a high-fat diet for 11weeks. In group four (DEN/CCl4/obese group) rats received high-fat diet for 30 days then received a single intraperitoneal injection of DEN (200 mg/kg body weight) followed by weekly subcutaneous injections of CCL4 (3 mg/kg body weight) for six weeks. At the end of the experimental period, rats were fasted overnight, anesthetized using diethyl ether and blood samples were withdrawn from retro-orbital plexus and collected in separation tubes, kept in a tilted position for 30 min at room temperature then centrifuged at 3000 r.p.m for 15 minutes to separate the serum for subsequent biochemical analysis. Moreover, the liver was collected from each rat, and divided into three parts. The first part was collected in eppendorf tubes with RNA later for used in RNA extraction and gene expression analysis. Second part was homogenized with sterile phosphate buffer saline to obtain tissue homogenate for used in the analysis of oxidative stress and antioxidants markers. The third part was preserved in 10% formalin for used in histopathological examination. The body weight was significantly decreased in DEN/CCl4 treated groups compared to all examined group but significantly increased in the obese group compared with the control group. Moreover, the body weight in DEN and CCl4/ obese treated rats was significantly lower than those of the obese group fed on a high-fat diet but still higher than DEN and CCl4 treated rats.The lipid profile including TC, TG, LDL-C, and VLDL-C was significantly increased meanwhile HDL-C was significantly decreased in all experimental groups compared with the control group. Moreover, parameters of the serum lipid profile insignificantly changed in DEN and CCl4/ obese treated rats when compared against the obese group. The result of this study showed that the activities of ALT, AST, ALP and level of total bilirubin and direct bilirubin in serum were increased in DEN/CCl4–treated group, while addition of high-fat diet-induced obesity showed a non-significant change in serum level of ALT, ALP, total and direct bilirubin but AST activity was significant increase in compared with control. Moreover, the serum activities of ALT, ALP, as well as serum levels of total and direct bilirubin were significantly elevated while AST activity was a significant decrease in DEN/CCl4/ obese treated rats compared with the obese group. Both ALT and AST activities were significantly decrease in DEN /CCl4/ obese compared to DEN/CCl4–treated group.The level of albumin in serum was decreased in DEN/CCl4 –treated group compared with the control group as well as DEN and CCl4/ obese treated group compared with the obese group, while it was non-significant changed in the obese group compared with the control group. Serum alpha-fetoprotein was increased in DEN/CCl4 –treated group compared with the control group as well as DEN and CCl4/ obese treated group comparing with the obese group. The levels of oxidative stress marker as MDA in liver tissue was increased in DEN/CCl4 –treated group, while it was non-significant changed in the obese group compared with the control group as well as DEN and CCl4/ obese treated group comparing with the obese group. While, DEN/CCl4/obese was significant decreased compared to DEN/CCl4–treated group. The antioxidant status in liver tissue, which was evaluated by measuring activities of SOD, catalase and level of GSH, were decreased in DEN/CCl4–treated group compared to control. While GSH concentration only was significant decrease with non-significant changed in SOD and catalase activity in the liver of obese rats when compared with the control rats. In DEN/CCl4/obese treated group, the hepatic CAT and GSH were insignificantly changed whilst hepatic SOD was significantly decreased when compared with obese rats but significantly increased when compared with DEN/CCl4 –treated group. The expression of Caspase-3 was decreased in DEN/CCl4 –treated group, as well as an obese treated group, compared with the control group, while it was upregulated in DEN/CCl4/obese treated.