title: Lactoferrin protects against chemical-induced rat liver fibrosis by inhibiting stellate cell activation.
abstract: 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.
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Tung
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Tang
authors.affiliation: Department of Bioresources, Da-Yeh University, Changhwa 515, Taiwan.
authors.forename: Hsiao-Ling
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan 404, Taiwan.
authors.forename: Shang-Hsun
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Tao-Yuan 333, Taiwan.
authors.forename: Kowit-Yu
authors.initials: KY
authors.lastname: Chong
authors.affiliation: Department of Animal Science and Biotechnology, Tunghai University, Taichung 407, Taiwan.
authors.forename: Winston T K
authors.initials: WT
authors.lastname: Cheng
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan; Rong Hsing Research Center for Translational Medicine, and Integrative Evolutionary Galliform Genomics Center, National Chung Hsing University, Taichung 402, Taiwan. Electronic address: chchen1@dragon.nchu.edu.tw.
authors.forename: Chuan-Mu
authors.initials: CM
authors.lastname: Chen
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004128:Dimethylnitrosamine / Q000633:toxicity; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000032:analysis; D007781:Lactoferrin / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography
chemical_list: D012333:RNA, Messenger; D007781:Lactoferrin; D004128:Dimethylnitrosamine; D006909:Hydroxyproline
keywords: dimethylnitrosamine; hepatic stellate cells; lactoferrin; liver fibrosis