The ameliorative effect of vinpocetine on liver fibrosis and bone changes in the bile-duct ligated rat

Vinpocetine is a drug that is widely used to treat vascular cognitive disorders in the old age. The drug has been shown to protect against hepatocellular damage caused by carbon tetrachloride in rats. In this study, vinpocetine was investigated for its ability to improve cholestatic hepatic injury and bone changes associated with bile duct ligation in rats. Rats with biliary obstruction induced by double ligation and section of the common bile duct were randomly and blindly assigned to receive either vinpocetine (2.1, 4.2, 8.4 mg/kg) or saline once a day orally, starting one day after surgery and continued for one month thereafter. At the end of the treatment period, rats were killed and analyzed for blood biochemistry, liver and bone histopathology. Compared to their sham-treated counterparts, bile duct-ligated (BDL) rats exhibited markedly elevated serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphate (ALP) as well markedly raised serum bilirubin level. Histopathological examination of BDL rats revealed focal necrosis, degenerated hepatocytes, bile duct hyperplasia and inflammatory cell infiltrates. Histochemical staining using Feulgen and Periodic acid-Schiff’s (PAS) staining showed depletion of liver glycogen and markedly decreased deoxyribonucleic acid (DNA) content in hepatocytes. Reduced osteocyte cellularity and few areas of regenerating bone were observed in BDL rats. The administration of vinpocetine to BDL rats resulted in dose-dependent decrease in serum ALT, AST, ALP activities by 33.6-64.4%, 17.5-43.9% and 26.5%-39.2%, respectively. Serum bilirubin decreased by 19% after 8.4 mg/kg of vinpocetine. The drug also resulted in amelioration of the pathological changes in the liver, increased glycogen and DNA content of hepatocytes and improved bone cellularity and increased bone regeneration dose-dependently. These findings suggest a beneficial effect for vinpocetine on liver damage and bone changes caused by biliary obstruction in rats.