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Cholestasis is one of the major determinants which causes hepatic injury and might lead to liver complications. In cholestasis, toxic bile acids accumulate with decrease in the capacity of detoxification. It can be stimulated experimentally by bile duct ligation (BDL) to block the bile flow from the liver. As for the treatment, lactoferrin (LF), the iron-binding glycoprotein, has been evaluated in various studies for the treatment of infections, inflammation, and cancer. This study aims to illustrate the curative effects of LF on BDL-induced hepatic injury in rats. Animals were randomly allocated into 4 groups: the first group is the control sham; the subjects of the second group have been subjected to a surgery of BDL; the latter procedure has been induced in the third group, 14 days later, they have been subjected to the treatment with LF (300 mg/kg/day, po) for two weeks; as for the last group, LF has been administered (300mg/kg/day, po) for two weeks. BDL elevated biomarkers of hepatocellular damage (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) and obstructive cholestatic injury (gamma-glutamyl transferase (γ-GT) and total bilirubin). In addition, it provoked oxidative stress manifested by increase in hepatic MDA and reduction of SOD with down-regulation of Nrf2/HO-1 pathway. LF treatment ameliorated these effects through its antioxidant activity by activation of Nrf2/HO-1 pathway that leads to decrease in hepatic MDA and elevation of SOD. In conclusion; lactoferrin alleviated hepatic injury induced by BDL via activating Nrf2 gene expression that might be led back to its antioxidant properties.

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