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    Therapeutic Effect of Melatonin on CCl4-Induced Fibrotic Liver Model by Modulating Oxidative Stress, Inflammation, and TGF-?1 Signaling Pathway in Pinealectomized Rats
    (Springer/Plenum Publishers, 2024) Cinar, Derya; Altinoz, Eyup; Elbe, Hulya; Bicer, Yasemin; Cetinavci, Dilan; Ozturk, Ipek; Colak, Tuncay
    The study aimed to determine the CCl4-induced liver fibrosis model in pinealectomized rats and biochemically, immunohistochemically, and histopathologically investigate the therapeutic effect of melatonin on liver fibrosis. The surgical procedure for pinealectomy was performed at the beginning of the study, and the sham and pinealectomized rats were administered CCl4 dissolved in corn oil (1:1) alone every other day to induce liver fibrosis or together with melatonin (10 mg/kg) therapy for 15 days. Melatonin is an essential therapeutic agent and offers an alternative therapeutic strategy in CCl4-induced liver fibrosis by suppressing inflammation, oxidative stress, and the TGF-beta 1 signaling pathway. Treatment with melatonin ameliorated CCl4-induced liver fibrosis by restoring hepatocellular damage and reducing plasma AST, ALT, and ALP values. Melatonin increases the activity of SOD and CAT, which are important enzymes for antioxidant defence, and raises GSH levels, which further enhances antioxidant function. Also, melatonin reduced hepatic inflammation (IL-6 and IL-1 beta) and oxidative stress indices. Moreover, histopathological changes and immunohistochemical expression of TGF-beta 1 were restored following melatonin supplementation in the CCl4-induced liver fibrosis model in pinealectomized rats. Our study shows that melatonin supplementation has a beneficial effect in protecting the liver fibrosis induced by CCl4 in pinealectomized rats.