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, Istvan Boldogh

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

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. Lipopolysaccharideinduced 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.

Original languageEnglish
Pages (from-to)67-79
Number of pages13
JournalInnate Immunity
Volume16
Issue number2
DOIs
Publication statusPublished - 2010 Apr
Externally publishedYes

Keywords

  • DNA damage
  • Lactoferrin
  • Mitochondria
  • Oxidative stress

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

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