title: Lactoferrin protects against acetaminophen-induced liver injury in mice.
abstract: Acetaminophen-induced liver injury (AILI) is a significant health problem and represents the most frequent cause of drug-induced liver failure in the United States. The development and implementation of successful therapeutic intervention strategies have been demanding, due to significant limitations associated with the current treatment for AILI. Lactoferrin (Lac), a glycoprotein present in milk, has been demonstrated to possess a multitude of biological functions. Our study demonstrated a profound protective effect of Lac in a murine model of AILI, which was not dependent on its iron-binding ability, inhibition of acetaminophen (APAP) metabolism, or a direct cytoprotective effect on hepatocytes. Instead, Lac treatment significantly attenuated APAP-induced liver sinusoidal endothelial cell dysfunction and ameliorated hepatic microcirculation disorder. This protective effect of Lac appeared to be dependent on hepatic resident macrophages (Kupffer cells [KCs]).
  
  
  CONCLUSIONS
  Collectively, our data indicate that Lac, through activation of KCs, inhibited APAP-induced liver sinusoidal endothelial cell damage and improved hepatic congestion, thereby protecting against AILI. These findings reveal the significant therapeutic potential of Lac during AILI and other types of liver diseases.
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado, Denver, CO 80045, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Yin
authors.forename: Linling
authors.initials: L
authors.lastname: Cheng
authors.forename: Michael
authors.initials: M
authors.lastname: Holt
authors.forename: Numsen
authors.initials: N
authors.lastname: Hail
authors.forename: Robert
authors.initials: R
authors.lastname: Maclaren
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ju
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D007781:Lactoferrin / Q000627:therapeutic use*; D008099:Liver / Q000098:blood supply / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008833:Microcirculation
chemical_list: D000082:Acetaminophen; D007781:Lactoferrin