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Abstract Phthalimide is an important pharmacophore and has a privileged structure in drug discovery . It has been reported that the phthalimide moiety is a very important biologically active pharmacophore. Antimicrobial properties of phthalimide derivatives were reported. A series of novel phthalimide analogs containing brominated indole moiety were synthesized compounds showed broad spectrum activity to words different fungi and potent anticancer activity on different cancer cell line. They showed ability to bind topoisomerase || DNA gyrase. Moreover, they augment caspase -3 levels and declined Bcl-2 expression. Liver fibrosis is a frequent event which follows a repeated or chronic insult of sufficient intensity to tigger a “wound healing “reaction. Characterized by excessive connective tissue deposition in extra Plan of the work: The experiments will be carried out on adult albino mice. Animals will be maintained at 25 °C± 2°C under standard conditions in the animal house. Animal care, maintenance and experiments were performed under the supervision of the Institutional Animal Ethics Committee. Animals will be divided into four groups: • group I: (normal control); mice without any treatment. • group II: (CCl4 model group); mice injected withCCl4 (0.4 mL/kg) mixed in olive oil at ratio (1:4) twice a week for 6 consecutive weeks. • group III: mice injected with CCl4 and i.p. treated with the phthalimide. • group IV: mice injected with CCl4 and i.p. treated with Thalidomide (reference drug). At the end of experiment, animal’s euthanasia will be done; liver tissues will be collected for estimation of the mentioned parameters: (1) Histopathology examination of liver. (2) Determination of Bcl-2, Caspase-3, VEGF and PECNA, and by immunohistochemistry. (3) Measurement of Malondialdehyde (MDA), Super oxide (4) dismutase (SOD), Catalase (CAT), and Glutathione per oxidase (GPx) concentration in liver tissues homogenates. (5) Determination of TNF-? level in liver tissues (6) 5-Determination of NF-?B-p65 protein level in liver tissues Histopathological examination of liver tissue 1- Normal mice: Normal hepatocytes arranged in cords around the central vein were presented in liver tissues. 2- the liver tissues of LI model group showed multiple histopathological changes demonstrated by centrilobular hepatic necrosis, fibroblastic cells proliferation 3- The treatment with phthalimide analog, (30 mg/kg body weight), improved these pathologic changes because there is no detectable fibrosis or necrosis while a mild degree of hepatic degeneration. 4- In the case of mice treated with thalidomide reference drug, (30 mg/kg body weight), it was found a centrilobular hepatic necrosis (arrow), midzonal, and periportal hepatic vacuolation. |