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

J Dairy Sci. 2014;97(6):3281-91. doi: 10.3168/jds.2013-7505. Epub 2014 Apr 14.


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 α-1(I) (ColIα-1) and α-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 ColIα-1 and α-smooth muscle actin, and suppressed the hydroxyproline content when compared with the DMN-treated group. Liver histopathology also showed that low-dose LF (100mg/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.

Keywords: dimethylnitrosamine; hepatic stellate cells; lactoferrin; liver fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Dimethylnitrosamine / toxicity
  • Disease Models, Animal
  • Hydroxyproline / analysis
  • Lactoferrin / pharmacology*
  • Lactoferrin / therapeutic use
  • Liver / chemistry
  • Liver / diagnostic imaging
  • Liver / pathology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / prevention & control*
  • Male
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Ultrasonography


  • RNA, Messenger
  • Lactoferrin
  • Dimethylnitrosamine
  • Hydroxyproline