الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Effects of harmaline on biochemical and molecular markers in serum and liver tissues of TA induced liver toxicity in mice were investigated. Sixty male mice, with average body weight 25-30 g were used in the experimental investigation of this study. Animals were housed in separate metal cages. Pure drinking water was supplied ad-libitum through specific nipple. Mice were kept at constant environmental and nutritional conditions throughout the period of experiment. The animals were left 7 days before the beginning of the experiment for acclimatization. Thioacetamide was used to induce liver cirrhosis. It was administered at a dose level of (150 mg/kg b. wt.) intraperitoneally twice weekly for 4 weeks. Experimental Design After acclimatization period, Mice were randomly distributed into 5 groups (12 mice per each) and treated as follows: group Ia (Normal control Group) mice fed with ordinary diet only without any treatment during the entire experimental period of 10 weeks . group Ib (HAL Group) mice received Harmaline at a dose level of (10 mg/kg b. wt.) intraperitoneally twice a week for 6 weeks. group II (TA Group) mice received Thioacetamide at a dose level of (150 mg/kg b. wt.) intraperitoneally twice a week for 4 weeks. group IIIa (Co-treated Group) mice received Thioacetamide + Harmaline respectively at the same dose level twice a week for 6 weeks. group IIIb (Treated Group) mice were treated with Harmaline for 6 weeks, starting after the date of being infected with Thioacetamide. Random blood samples and liver tissue specimens were collected from all animals’ groups (normal control and experimental groups) at the end of the experiment (10 weeks). Then, in parallel to the histopathological analysis, the anti-cirrhotic effects of harmaline by elucidate the role of adiponectin and other markers were investigated in intoxicated thioacetamide model. The biochemical analysis included Adiponectin (ADN), Transforming growth factor-β1 (TGF-β1), Peroxisome proliferator-activated receptor-γ (PPAR-γ), Tissue inhibitors of metalloproteinase1 (TIMP-1), antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD), also glutathione level (GSH), liver Malondialdehyde (MDA) , nitric oxide (NO) and Arginase-1. Also, liver and kidney function tests (ALT, AST, γ-GT, ALB, TP, urea, and creatinine) are measured. The histopathological examination included the H&E changes liver tissue. Harmaline injection along the period of the experiment induced great biochemical and histopathological changes in the liver. The results of the present study could be summarized as follows: The results indicated that harmaline administration cause significant suppression of oxidative stress and inflammatory response. Harmaline dose cause significant decrease in liver serum indices; AST, ALT and γ-GT as compared to TA control group. Moreover, harmaline exerted protective activity against TA-induced oxidative stress as evidenced by significant decrease in liver MDA content and NO, as well as, significant increase in SOD enzyme, liver GSH content and liver CAT activities as compared to TA control group. Harmaline significantly reduced inflammatory markers TGF-β1 and TIMP-1 as compared to TA control group. Additionally, it was found to be a potent effector on adiponectin and also PPAR-γ, since harmaline induce adiponectin liver expression in our model, this could represent a possible pathway for the anti-cirrhotic effect of Harmaline. The results exhibited that injection of mice with TA induced liver cirrhosis and this was confirmed by the histopathological studies which showed changes in the liver architecture. The livers treated with thioacetamide showed severe congestion and dilatation of the central vein and portal blood vessels. Perivascular mononuclear leukocytic infiltrations were also seen. Treatment with harmaline combined with TA-dose in GIIIa group or after it for treatment as in GIIIb group ameliorated the biochemical and histopathological disturbances appeared in the liver parameters under investigation. Also, the present study showed that harmaline repressed TA-induced increase in protein expression of pro-inflammatory markers which could be a direct effect or through activation of adiponectin. Adiponectin is a major effector in recovery from liver injury.