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Lactoferrin protects against acetaminophen-induced liver injury in mice†
Article first published online: 30 NOV 2009
Copyright © 2009 American Association for the Study of Liver Diseases
Volume 51, Issue 3, pages 1007–1016, March 2010
How to Cite
Yin, H., Cheng, L., Holt, M., Hail, N., MacLaren, R. and Ju, C. (2010), Lactoferrin protects against acetaminophen-induced liver injury in mice. Hepatology, 51: 1007–1016. doi: 10.1002/hep.23476
Potential conflict of interest: Nothing to report.
- Issue published online: 2 MAR 2010
- Article first published online: 30 NOV 2009
- Accepted manuscript online: 30 NOV 2009 12:00AM EST
- Manuscript Accepted: 23 OCT 2009
- Manuscript Received: 12 MAY 2009
- U.S. National Institutes of Health. Grant Number: RO1 ES012914
- American College of Clinical Pharmacy Frontiers Career Development Research Award
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]). Conclusion: 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. (HEPATOLOGY 2010.)