Merve Aykaç - Department of Medical Biology, Faculty of Medicine, Ataturk University, Erzurum, Turkey
Eda Balkan - Department of Medical Biology, Faculty of Medicine, Ataturk University, Erzurum, Turkey
Semin Gedi̇kli - Department of Histology and Embrylogy, Faculty of Veterinary, Ataturk University, Erzurum, Turkey
Nurinnisa Öztürk - Department of Medical Biochemistry, Faculty of Medicine, Ataturk University, Erzurum,Turkey

Objective(s): Liver fibrosis is a wound healing response characterized by excessive accumulation of extracellular matrix proteins. This study aimed to investigate the effects of resveratrol treatment on the TGF-β/SMAD signaling pathway and related biochemical parameters, apoptosis, and liver regeneration phenobarbital-CCl۴ induced hepatic fibrosis rat model. Materials and Methods: This model was created through phenobarbital and CCl۴ (۰.۲–۰.۳۵ ml/kg). Resveratrol (۱ mg/kg/day) was administered to the fibrosis and control groups. Immunohistochemical staining was performed to evaluate αSMA, TGF-β۱, and PCNA in liver tissue. The TUNEL method and Masson’s Trichome staining were used to determine apoptosis and collagen accumulation. AST, ALP, ALT, total protein, and total bilirubin levels were measured to determine biochemical status. SMAD۲, SMAD۳, SMAD۴, and SMAD۷ expression levels were measured to determine TGF-β۱ related hepatic fibrosis. Results: The SMAD۲, SMAD۳, and SMAD۴ mRNA expression levels were increased and the SMAD۷ mRNA expression level was decreased in the fibrosis control group. The SMAD۷ mRNA expression level was higher in the phenobarbital-CCl۴ induced resveratrol treated group. Increased biochemical parameters indicating hepatic damage, increased number of apoptotic cells, and collagen accumulation surrounding the central vein were observed in the fibrosis group compared with the other groups. It was concluded that administration of resveratrol ameliorates the adverse effects of hepatic fibrosis by regulating biochemical parameters, controlling TGF-β۱/SMAD signaling, enhancing tissue regeneration, and reducing apoptosis in liver cells. Conclusion: Resveratrol can be a beneficial option for the prevention of liver damage in a phenobarbital-CCl۴ induced hepatic fibrosis.

Carbon tetrachloride (CCl۴), Hepatic fibrosis, Liver, Resveratrol, Transforming growth factor β/small mother against decapentaplegic (TGF-β/SMAD) signalling, SMAD Proteins