Lactoferrin protects against chemical-induced rat liver fibrosis by inhibiting stellate cell activation

Liver diseases, which can be caused by alcohol abuse, chemical intoxication, viral hepatitis infection, and autoimmune disorders, are a significant health issue because they can develop into liver fibrosis and cirrhosis. Lactoferrin (LF), a siderophilic protein with 2 iron-binding sites, has been demonstrated to possess a multitude of biological functions, including antiinflammation, anticancer, and antimicrobial effects, as well as immunomodulatory-enhancing functions. In the current study, we induced hepatotoxicity in rats with dimethylnitrosamine (DMN) to establish a situation that would enable us to evaluate the hepatoprotective effects of LF against hepatic injury. Our results showed that DMN-induced hepatic pathological damage significantly decreased the body weight and liver index, increased the mRNA and protein levels of collagen alpha-1(I) (ColI alpha-1) and alpha-smooth muscle actin, and increased the hydroxyproline content. However, treatment with LF significantly increased body weight and liver index, decreased the mRNA and protein levels of ColI alpha-1 and alpha-smooth muscle actin, and suppressed the hydroxyproline content when compared with the DMN-treated group. Liver histopathology also showed that low-dose LF (100 mg/kg of body weight) or high-dose LF (300 mg/kg of body weight) could significantly reduce the incidences of liver lesions induced by DMN. These results suggest that the LF exhibits potent hepatoprotection against DMN-induced liver damage in rats and that the hepatoprotective effects of LF may be due to the inhibition of collagen production and to stellate cell activation.