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First published online September 1, 2009

Lactoferrin decreases LPS-induced mitochondrial dysfunction in cultured cells and in animal endotoxemia model

Marian L. Kruzel, Jeffrey K. Actor, Zsolt Radak, Attila Bacsi, Alfredo Saavedra-Molina, and Istvan BoldoghView all authors and affiliations
Volume 16, Issue 2
https://doi.org/10.1177/1753425909105317

Abstract

Lactoferrin is a non-heme iron-binding glycoprotein, produced by mucosal epithelial cells and granulocytes in most mammalian species. It is involved in regulation of immune responses, possesses anti-oxidant, anti-carcinogenic, anti-inflammatory properties, and provides protection against various microbial infections. In addition, lactoferrin has been implicated in protection against the development of insult-induced systemic inflammatory response syndrome (SIRS) and its progression into septic conditions in vivo. Here we show a potential mechanism by which lactoferrin lessens oxidative insult at the cellular and tissue levels after lipopolysaccharide (LPS) exposure. Lactoferrin pretreatment of cells decreased LPS-mediated oxidative insults in a dose-dependent manner. Lipopolysaccharide-induced oxidative burst was found to be of mitochondrial origin, and release of reactive oxygen species (ROS) was localized to the respiratory complex III. Importantly, lactoferrin nearly abolished LPS-induced increases in mitochondrial ROS generation and the accumulation of oxidative damage in the DNA. In vivo, pretreatment of experimental animals with lactoferrin significantly (P<0.05) lowered LPS-induced mitochondrial dysfunction as shown by both decreased release of H2O2 and DNA damage in the mitochondria. In contrast, deferoxamine, an iron chelating compound, provided only partial protection in LPS-treated animals. Together, these data suggest that lactoferrin protects against oxidative insult at the mitochondrial level, and indicate a potential utility of lactoferrin in prevention and treatment of SIRS.

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Published In

Volume 16, Issue 2
Pages: 67 - 79
Article first published online: September 1, 2009
Issue published: April 2010

Keywords

  1. Lactoferrin
  2. oxidative stress
  3. mitochondria
  4. DNA damage

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© SAGE Publications 2010.
PubMed: 19723832

Authors

Affiliations

Marian L. Kruzel
Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center at Houston Medical School, Texas, USA
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Jeffrey K. Actor
Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center at Houston Medical School, Texas, USA
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Zsolt Radak
Institute of Sport Science, Faculty of Physical Education and Sport Science, Semmelweis University, Budapest, Hungary
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Attila Bacsi
Institute of Immunology, University of Debrecen, Debrecen, Hungary
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Alfredo Saavedra-Molina
Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, México
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Istvan Boldogh
Department of Microbiology and Immunology, and University of Texas Medical Branch at Galveston, Texas, USA, [email protected]
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