Dietary lactoferrin alleviates age-related lacrimal gland dysfunction in mice

PLoS One. 2012;7(3):e33148. doi: 10.1371/journal.pone.0033148. Epub 2012 Mar 27.

Abstract

Background: Decrease in lacrimal gland secretory function is related to age-induced dry eye disease. Lactoferrin, the main glycoprotein component of tears, has multiple functions, including anti-inflammatory effects and the promotion of cell growth. We investigated how oral administration of lactoferrin affects age-related lacrimal dysfunction.

Methods and findings: Twelve-month-old male C57BL/6Cr Slc mice were randomly divided into a control fed group and an oral lactoferrin treatment group. Tear function was measured at a 6-month time-point. After euthanasia, the lacrimal glands were subjected to histological examination with 8-hydroxy-2'-deoxyguanosine (8-OHdG) antibodies, and serum concentrations of 8-OHdG and hexanoyl-lysine adduct (HEL) were evaluated. Additionally, monocyte chemotactic protein-1(MCP-1) and tumor necrosis factor-α (TNF-α) gene expression levels were determined by real-time PCR. The volume of tear secretion was significantly larger in the treated group than in the control. Lactoferrin administration reduced inflammatory cell infiltration and the MCP-1 and TNF-α expression levels. Serum concentrations of 8-OHdG and HEL in the lactoferrin group were lower than those in the control group and were associated with attenuated 8-OHdG immunostaining of the lacrimal glands.

Conclusion: Oral lactoferrin administration preserves lacrimal gland function in aged mice by attenuating oxidative damage and suppressing subsequent gland inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Administration, Oral
  • Aging*
  • Animals
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / pharmacology
  • Chemokine CCL2 / genetics
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / blood
  • Deoxyguanosine / metabolism
  • Dietary Supplements
  • Gene Expression / drug effects
  • Immunohistochemistry
  • Lacrimal Apparatus / drug effects*
  • Lacrimal Apparatus / metabolism
  • Lacrimal Apparatus / ultrastructure
  • Lacrimal Apparatus Diseases / pathology
  • Lacrimal Apparatus Diseases / physiopathology
  • Lacrimal Apparatus Diseases / prevention & control*
  • Lactoferrin / administration & dosage
  • Lactoferrin / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission
  • Random Allocation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tears / drug effects
  • Tears / metabolism
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Anti-Infective Agents
  • Chemokine CCL2
  • Tumor Necrosis Factor-alpha
  • 8-Hydroxy-2'-Deoxyguanosine
  • Lactoferrin
  • Deoxyguanosine