الفهرس 
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Abstract
This study was carried out at the Faculty of Veterinary Medicine, Alexandria University to investigate molecular evaluation of some signalling molecules in experimentally induced hepatocellular carcinoma in rats and to study protective effect of propolis in relation to silymarin. Using a total of 110 male albino rats aging 90±10 days old and were divided into eleven equal groups (10 rats/ group) as following: Group( 1): control group: kept on basal ration and water ad libitum. group (2): Vehicle control: kept on basal ration and subcutaneous injection of olive oil at dose of (3ml/kg b.wt/twice/week). group (3): Silymarin control: kept on basal ration and silymarin (100 mg/kg b.wt/ oral/daily group (4): Propolis dose I control: kept on basal ration + propolis (100 mg/kg b.wt/ oral/daily) group (5): Propolis dose II control: kept on basal ration + propolis (150 mg/kg b.wt/ oral/daily) group (6): Propolis dose III control: kept on basal ration + propolis (200 mg/kg b.wt/ oral/daily group (7): Positive control (HCC): kept on basal ration + DEN (200 mg/ kg b.wt/i.p/ once was dissolved in saline 0.9%) two weeks later CCl4 (3 ml/ kg b.wt/ sc/ twice/ week was dissolved in olive oil in ratio of 1:1v/v) till end of experiment group (8): HCC+ silymarin group (9): HCC+ propolis dose I group (10): HCC+ propolis dose II group (11): HCC+ propolis dose III The experiment lasted for 6 months and every one month and half three rats from each group were randomly taken to confirm incidence of hepatic cancer by measuring tumor markers and histopathological examination of liver tissueb Blood samples were collected from eye canthus of rats of all groups after six monthes and serum was separated for determination of: Tumor markers. Liver functions. Liver tissues were collected for evaluation of: Liver weight and relative liver weight Hepatic nodule incidence. Lipid peroxidation, reduced glutathione and antioxidant enzymes (Catalase , Glutathione peroxidase and superoxide dismutase). Molecular evaluation of some signalling molecules Histopathological examination of liver Our results and Statistical analysis revealed the following: 1- Body weight was markedly decreased in rats with hcc while liver weight and RLW were significantly increased. 2- Usage of silymarin and propolis maintained body weight and decreased the increase in liver weight. 3- Hcc rats had developed nodules in liver 4- Nodule incidence decreased significantly in groups protected with silymarin and propolis. 5- Tumor markers increased significantly in hcc rats, protection with silymarin and propolis sucessfully decreased their level 6-Total protein , albumin and A/G ratio were markedly decreased in hcc rats. 7-Usage of silymarin and propolis increased level of total protein, albumin and A/G ratio 8-Serum bilirubin was markedly increased in rats treated with DEN+CCl4 .Protection with silymarin and propolis reduced its level effectively 9-Liver function enzymes were significantly increased in hcc rats and natural products showed improvement in liver functiion. 8- Lipid peroxidation level was markedly increased in hcc rats while, GSH and antioxidant enzymes were decreased. 9-Administration of silymarin and propolis restore balance in oxidative stress and increased antioxidants 10- p21 showed low expression in hcc rats while, Mdm2 was highly expressed . 12- Silymarin and propolis sucessfully increase expression of p21 and decrease expression of Mdm2 13- Liver tissues of the control groups: showed normal histological criteria of the hepatic cords and hepatocytes while, liver of hcc rats showed prominent carcinogenic changes and formation of fibrous tissues, congestion of blood vesseles and marked fatty changes. marked fatty. 14- silymarin and propolis treatment showed few carcinogenic changes and minute fibrous changes.