Abstract

The primary treatment for chronic liver disease (CLD) involves dietary and non-dietary interventions. However, when CLD progresses to end-stage liver disease, liver transplantation becomes the only viable option, despite challenges such as donor shortages, transplant rejection, immunosuppressive drug complications, and high costs. To address the urgent need for post-transplantation liver regeneration, the growing focus is emphasized on the stimulation of liver regeneration by pharmacological intervention, even in non-transplanted individuals or those with early liver complications. The objective of this work was to activate the Wnt/β-catenin signaling pathway by blocking GSK-3β to enhance the regeneration of hepatocytes and the liver. A partial hepatectomy was performed on 44 rats, with the animals divided into six groups and assessed from postoperative days 1 to 8. The effects of the GSK-3β inhibitor CHIR99021 (6.25 mg/kg/bw) on hepatocyte regeneration and hepatoprotection were evaluated using biochemical, histopathological methods, and docking studies. It was indicated that both single and repeated doses of CHIR99021 notably improved lipid profiles, liver function, and reduced oxidative stress in partial hepatectomized rats on the third and seventh day as compared to those without drug treatment. Histopathological assessments confirmed substantial hepatocyte regeneration after CHIR99021 treatment, supported by docking studies that showed notable binding interactions with important amino acids of the protein. Mitotic cell phase determination also validated the histopathological findings in different rodent groups. In conclusion, pharmacological stimulation of the Wnt/β-catenin pathway through GSK-3β inhibition with CHIR99021 demonstrated promising results in promoting hepatocyte regeneration, potentially offering a new treatment strategy for liver regeneration.

Key words: Partial hepatectomy, GSK-3 β inhibition, Liver regeneration, Health, Mortality, Pharmacy health.