Lactoferrin decreases LPS-induced mitochondrial dysfunction in cultured cells and in animal endotoxemia model
Open accessAbstract
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 H 2 O 2 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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In an endotoxemic mouse model, lactoferrin decreased LPS-induced oxidative burst and reactive oxygen species in cultured cells and attenuated mitochondrial dysfunction in liver of endotoxemic mice.
“In an endotoxemic mouse model, lactoferrin, a nonheme iron-binding glycoprotein, decreased LPS-induced oxidative burst and reactive oxygen species in cultured cells and attenuated mitochondrial dysfunction in liver of endotoxemic mice [86].”
From The utility of iron chelators in the management of inflammatory disorders (2015) · cites this paper as [86]
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Cites
Yakes, F. M., & Van Houten, B. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.2.514 · Cited by 1,854 · see citing works
Human Cells Lacking mtDNA: Repopulation with Exogenous Mitochondria by Complementation
King, M. P., & Attardi, G. M. (1989) · Science · doi:10.1126/science.2814477 · Cited by 1,659 · see citing works
Production of Reactive Oxygen Species by Mitochondria
Chen, Q., Vazquez, E. J., Moghaddas, S., Hoppel, C. L., & Lesnefsky, E. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304854200 · Cited by 1,616 · see citing works
Zhou, M., Diwu, Z. J., Panchuk-Voloshina, N., & Haugland, R. P. (1997) · Analytical Biochemistry · doi:10.1006/abio.1997.2391 · Cited by 1,400 · see citing works
Identification of the bactericidal domain of lactoferrin
Bellamy, W., Takase, M., Yamauchi, K., Wakabayashi, H., Kawase, K., & TOMITA, M. (1992) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/0167-4838(92)90346-f · Cited by 890 · see citing works
Brittenham, G. M., Griffith, P. M., Nienhuis, A. W., McLaren, C. E., Young, N. S., Tucker, E. E., Allen, C. J., Farrell, D. E., & Harris, J. W. (1994) · New England Journal of Medicine · doi:10.1056/nejm199409013310902 · Cited by 822 · see citing works
Zhao, H., Kalivendi, S., Zhang, H., Joseph, J., Nithipatikom, K., Vásquez-Vivar, J., & Kalyanaraman, B. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00142-4 · Cited by 803 · see citing works
Antiviral activities of lactoferrin
van der Strate, B. W. A., Beljaars, L., Molema, G., Harmsen, M. C., & Meijer, D. K. F. (2001) · Antiviral Research · doi:10.1016/s0166-3542(01)00195-4 · Cited by 468 · see citing works
Oxidative Innate Immune Defenses by Nox/Duox Family NADPH Oxidases
Rada, B., & Leto, T. L. (2008) · KARGER eBooks · doi:10.1159/000136357 · Cited by 449 · see citing works
Lactoferrin: A Multifunctional Glycoprotein Involved in the Modulation of the Inflammatory Process
Baveye, S., Elass, E., Mazurier, J., Spik, G., & Legrand, D. (1999) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.1999.049 · Cited by 340 · see citing works
Mitochondrial dysfunction in septic shock and multiple organ dysfunction syndrome
Crouser, E. D. (2004) · Mitochondrion · doi:10.1016/j.mito.2004.07.023 · Cited by 322 · see citing works
Inactivation of succinate dehydrogenase by 3-nitropropionate.
Coles, C. J., Edmondson, D. E., & Singer, T. P. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50574-3 · Cited by 307 · see citing works
Nuclear and mitochondrial DNA repair: similar pathways?
Larsen, N. B., Rasmussen, M., & Rasmussen, L. J. (2005) · Mitochondrion · doi:10.1016/j.mito.2005.02.002 · Cited by 289 · see citing works
Endotoxin-induced mitochondrial damage correlates with impaired respiratory activity
Crouser, E. D., JULIAN, M. W., Blaho, D. V., & Pfeiffer, D. R. (2002) · Critical Care Medicine · doi:10.1097/00003246-200202000-00002 · Cited by 277 · see citing works
Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis
Suliman, H. M. B., Welty‐Wolf, K. E., Carraway, M. S., Tatro, L. G., & Piantadosi, C. A. (2004) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.07.005 · Cited by 269 · see citing works
Analysis of Gene-Specific DNA Damage and Repair Using Quantitative Polymerase Chain Reaction
Ayala‐Torres, S., Chen, Y., Svoboda, T., Rosenblatt, J. I., & Houten, B. V. (2000) · Methods · doi:10.1006/meth.2000.1054 · Cited by 263 · see citing works
Pang, Z., & Geddes, J. W. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-09-03064.1997 · Cited by 248 · see citing works
Buchet, K., & Godinot, C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.36.22983 · Cited by 231 · see citing works
N-acetylcysteine and neurodegenerative diseases: Basic and clinical pharmacology
Arakawa, M., & Ito, Y. (2007) · The Cerebellum · doi:10.1080/14734220601142878 · Cited by 206 · see citing works
Antiinflammatory activities of lactoferrin
Conneely, O. M. (2001) · Journal of the American College of Nutrition · doi:10.1080/07315724.2001.10719173 · Cited by 205 · see citing works
Classical Inhibitors of NOX NAD(P)H Oxidases Are Not Specific
Aldieri, E., Riganti, C., Polimeni, M., Gazzano, E., Lussiana, C., Campia, I., & Ghigo, D. (2008) · Current Drug Metabolism · doi:10.2174/138920008786049285 · Cited by 201 · see citing works
Cells depleted of mitochondrial DNA (p0) yield insight into physiological mechanisms
Chandel, N. S., & Schumacker, P. T. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00783-8 · Cited by 198 · see citing works
Seo, B. B., Kitajima‐Ihara, T., Chan, E. K. L., Scheffler, I. E., Matsuno‐Yagi, A., & Yagi, T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9167 · Cited by 187 · see citing works
Bhakat, K. K., Mokkapati, S. K., Boldogh, I. R., Hazra, T. K., & MITRA, S. P. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.5.1654-1665.2006 · Cited by 176 · see citing works
Self-citationMitochondria contribute to LPS-induced MAPK activation via uncoupling protein UCP2 in macrophages
Emre, Y., Hurtaud, C., Nübel, T., Criscuolo, F., Ricquier, D., & Cassard, A. (2007) · Biochemical Journal · doi:10.1042/bj20061430 · Cited by 172 · see citing works
von JAGOW, G., & Ohnishi, T. (1985) · FEBS Letters · doi:10.1016/0014-5793(85)80929-7 · Cited by 170 · see citing works
Mitochondrial Respiratory Complex I Regulates Neutrophil Activation and Severity of Lung Injury
Żmijewski, J. W., Lorne, E., Zhao, X., Tsuruta, Y., Sha, Y., Liu, G., Siegal, G. P., & Abraham, E. H. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200710-1602oc · Cited by 167 · see citing works
A comparative study of oxidative DNA damage in mammalian spermatozoa
Bennetts, L. E., & Aitken, R. J. (2005) · Molecular Reproduction and Development · doi:10.1002/mrd.20285 · Cited by 163 · see citing works
Measuring Oxidative mtDNA Damage and Repair Using Quantitative PCR
Santos, J. H., Mandavilli, B. S., & Houten, B. V. (2003) · Humana Press eBooks · doi:10.1385/1-59259-284-8:159 · Cited by 158 · see citing works
Postlipopolysaccharide Oxidative Damage of Mitochondrial DNA
Suliman, H. B., Carraway, M. S., & Piantadosi, C. A. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200206-518oc · Cited by 153 · see citing works
Lactoferrin Content of Peripheral Blood Cells
Bennett, R. M., & Kokocinski, T. (1978) · British Journal of Haematology · doi:10.1111/j.1365-2141.1978.tb03620.x · Cited by 139 · see citing works
Kruzel, M. L., Harari, Y., Mailman, D. S., Actor, J. K., & Zimecki, M. (2002) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2002.01956.x · Cited by 138 · see citing works
Self-citationSchanbacher, F. L., Goodman, R. E., & Talhouk, R. (1993) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(93)77725-5 · Cited by 134 · see citing works
Mitochondrial mechanisms of sepsis-induced organ failure.
Exline, M. C., & Crouser, E. D. (2008) · PubMed · doi:10.2741/3061 · Cited by 133 · see citing works
Zagulski, T., Lipiński, P., Zagulska, A., Broniek, S., & Jarzabek, Z. (1989) · PubMed Central · Cited by 131 · see citing works
Miller, S. W., Trimmer, P. A., Parker, W. D., & Davis, R. E. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.67051897.x · Cited by 127 · see citing works
Molecular Events in the Cardiomyopathy of Sepsis
Flierl, M. A., Rittirsch, D., Huber-Lang, M. S., Sarma, J. V., & Ward, P. A. (2008) · Molecular Medicine · doi:10.2119/2007-00130.flierl · Cited by 127 · see citing works
Caccavo, D., Pellegrino, N. M., Altamura, M., Rigon, A., Amati, L., Amoroso, A., & Jirillo, E. (2002) · Journal of Endotoxin Research · doi:10.1179/096805102125001000 · Cited by 124 · see citing works
Yamada, H., Arai, T., Endo, N., et al. (2005) · Life Sciences · doi:10.1016/j.lfs.2005.05.106 · Cited by 121 · see citing works
Kruzel, M. L., Bácsi, A., Choudhury, B. K., Sur, S. A., & Boldogh, I. R. (2006) · Immunology · doi:10.1111/j.1365-2567.2006.02417.x · Cited by 114 · see citing works
Self-citationBiomarkers of oxidative damage to DNA and repair
Loft, S. H., Danielsen, P. H., Mikkelsen, L., Risom, L., Forchhammer, L., & Möller, P. (2008) · Biochemical Society Transactions · doi:10.1042/bst0361071 · Cited by 109 · see citing works
Lactoferrin Protects Gut Mucosal Integrity During Endotoxemia Induced by Lipopolysaccharide in Mice
Kruzel, M. L., Harari, Y., Chen, C.-Y., & Castro, G. A. (2000) · Inflammation · doi:10.1023/a:1006935908960 · Cited by 106 · see citing works
Self-citationLactoferrin and the Inflammatory Response
Baynes, R. D., & Bezwoda, W. R. (1994) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-2548-6_13 · Cited by 89 · see citing works
Dobson, A. W., Grishko, V. I., LeDoux, S. P., Kelley, M. R., Wilson, G. L., & Gillespie, M. N. (2002) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00443.2001 · Cited by 87 · see citing works
Depletion of excessive liver iron stores with desferrioxamine
Cohen, A. R., Martin, M., & Schwartz, E. (1984) · British Journal of Haematology · doi:10.1111/j.1365-2141.1984.tb06096.x · Cited by 82 · see citing works
Mandavilli, B. S., Boldogh, I. R., & Houten, B. V. (2005) · Molecular Brain Research · doi:10.1016/j.molbrainres.2004.10.033 · Cited by 77 · see citing works
Self-citationInduction of the Human Oxidized Base-specific DNA Glycosylase NEIL1 by Reactive Oxygen Species
Das, A., Hazra, T. K., Boldogh, I. R., MITRA, S. P., & Bhakat, K. K. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505526200 · Cited by 73 · see citing works
Self-citationLactoferrin in health and disease.
Kruzel, M. L., Actor, J. K., Boldogh, I. R., & Zimecki, M. (2007) · PubMed · Cited by 72 · see citing works
Self-citationBoldogh, I. R., Roy, G., Lee, M. S., Bácsi, A., Hazra, T. K., Bhakat, K. K., Das, G. C., & MITRA, S. P. (2003) · Toxicology · doi:10.1016/j.tox.2003.08.013 · Cited by 62 · see citing works
Self-citationMitochondrial Dysfunction in Sepsis: Evidence from Bacteraemic Baboons and Endotoxaemic Rabbits
Gellerich, F. N., Trumbeckaitė, S., Opalka, J. R., et al. (2002) · Bioscience Reports · doi:10.1023/a:1016017224003 · Cited by 46 · see citing works
Iron Release from Recombinant N-lobe and Mutants of Human Transferrin
Zak, O., Aisen, P., Crawley, J. B., et al. (1995) · Biochemistry · doi:10.1021/bi00044a020 · Cited by 46 · see citing works
Bácsi, A., Woodberry, M. W., Widger, W. R., Papaconstantinou, J., MITRA, S. P., Peterson, J. W., & Boldogh, I. R. (2006) · Mitochondrion · doi:10.1016/j.mito.2006.07.008 · Cited by 40 · see citing works
Self-citationIncreased ROS generation in subsets of OGG1 knockout fibroblast cells
Bácsi, A., Chodaczek, G., Hazra, T. K., Konkel, D. A., & Boldogh, I. R. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.09.005 · Cited by 38 · see citing works
Self-citationRodgers, S. J., & Raymond, K. N. (1983) · Journal of Medicinal Chemistry · doi:10.1021/jm00357a022 · Cited by 37 · see citing works
Ebselen: A thioredoxin reductase-dependent catalyst for α-tocopherol quinone reduction
FANG, J., Zhong, L., Zhao, R., et al. (2005) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2005.02.022 · Cited by 34 · see citing works
Lactoferrin and immunologic dissonance: clinical implications.
Kruzel, M. L., & Zimecki, M. (2002) · PubMed · Cited by 31 · see citing works
Self-citation
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Research works printed but not linked: 2
- [23]Bespalov IA Bond JP Purmal AA Wallace SS Melamede RJ FAbs specific for 8-oxoguanine: control of DNA binding J Mol Biol 1999 293 1085 1095 10547287
- [49]Kluepfel D Sehgal SN Vezina C Antimycin A components. I. Isolation and biological activity J Antibiot (Tokyo) 1970 23 75 80 5416654
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Legrand, D. (2012) · Biochemistry and Cell Biology · doi:10.1139/o11-056 · Cited by 193 · see citing works
The utility of iron chelators in the management of inflammatory disorders
Lehmann, C., Islam, S., Jarosch, S., Zhou, J., Hoskin, D., Greenshields, A., Al-Banna, N., Sharawy, N., Sczcesniak, A., Kelly, M., et al. (2015) · Mediators of Inflammation · doi:10.1155/2015/516740 · Cited by 54 · see citing works
“In an endotoxemic mouse model, lactoferrin, a nonheme iron-binding glycoprotein, decreased LPS-induced oxidative burst and reactive oxygen species in cultured cells and attenuated mitochondrial dysfunction in liver of endotoxemic mice [86].”
Background
- Authors
- Kruzel, M. L., Actor, J. K., Radak, Z., Bacsi, A., Saavedra-Molina, A., & Boldogh, I.
- Affiliations
- The University of Texas Health Science Center at Houston (US)
- Semmelweis University (HU)
- Institute of Immunology, University of Debrecen, Debrecen, Hungary
- Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, México
- The University of Texas Medical Branch at Galveston (US)
- Venue
- Innate Immunity
- Publisher
- SAGE Publications
- Published
- 2009-09-01
- Volume
- 16
- Issue
- 2
- Pages
- 67-79
- ISSN
- 1753-4259 (ISSN-L)
- 1753-4267
- PMC
- PMC3030479
- OpenAlex
- W1978667507
- Cited by
- 69
- References
- 56
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 1 · 2015: 6 · 2014: 3 · 2013: 3 · 2012: 7
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Innate Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion)
- Funders
- U.S. Public Health Service (EOS 0 06677)
- National Institute on Aging (P01AG021830)
- National Institute of General Medical Sciences (R41GM079810)
- National Institute of Allergy and Infectious Diseases (AI062885-01, P01AI062885)
- National Institute of Environmental Health Sciences (P30ES006676)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- lactoferrin, lipopolysaccharide, mitochondrial dysfunction, oxidative stress, reactive oxygen species, respiratory complex III, DNA damage, endotoxemia, systemic inflammatory response syndrome, sepsis, deferoxamine, iron chelation, respiratory burst
- MeSH terms
- Animals, Deferoxamine, Disease Models, Animal, DNA Damage, Dose-Response Relationship, Immunologic, Epithelial Cells, Humans, Hydrogen Peroxide, Lactoferrin, Lipopolysaccharides, Mice, Inbred BALB C, Mitochondria, Monocytes, Electron Transport Complex III, Siderophores, Reactive Oxygen Species, Oxidative Stress, Endotoxemia, U937 Cells, Mice
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