Recombinant human lactoferrin enhances the efficacy of triple therapy in mice infected with Helicobacter pylori

Int J Mol Med. 2015 Aug;36(2):363-8. doi: 10.3892/ijmm.2015.2251. Epub 2015 Jun 17.

Abstract

Helicobacter pylori (H. pylori) is a life-threatening pathogen which causes chronic gastritis, gastric ulcers and even stomach cancer. Treatment normally involves bacterial eradication; however, this type of treatment only has a rate of effectiveness of <80%. Thus, it is a matter of some urgency to develop new therapeutic strategies. Lactoferrin, a member of the transferrin family of iron-binding proteins, has been proven to be effective in removing a vast range of pathogens, including H. pylori. In the present study, we examined the effectiveness of recombinant human lactoferrin (rhLf) isolated from transgenic goats as a treatment for H. pylori in vitro and in vivo. For the in vivo experiments, BALB/c mice received an intragastric administration of 0.1 ml of a suspension of H. pylori. The mice were then divided into 4 groups: group A, treated with saline; group B, treated with 1.5 g of rhLF; group C, treated with the standard triple therapy regimen; and group D, treated with the standard triple therapy regimen plus.5 g of rhLF. Following sacrifice, the stomach tissues of the mice were histologically examined for the presence of bacteria. For the in vitro experiments, the bacteria were cultured in BHI broth and RT-qPCR and western blot analysis were carried out to determine the mRNA and protein levels of virulence factors (CagA and VacA) in the cultures. Our results revealed that rhLf not only inhibited the growth of H. pylori, but also suppressed the expression of two major virulence factors. Moreover, rhLf markedly increased bacterial eradication and effectively reduced the inflammatory response when combined with the standard triple therapy regimen. These results provide evidence supporting the use of rhLF as an adjuvant to traditional therapeutic strategies in the treatment of H. pylori.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Drug Synergism
  • Gene Expression Regulation, Bacterial / drug effects
  • Goats
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / immunology
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology
  • Helicobacter pylori / drug effects*
  • Helicobacter pylori / growth & development
  • Humans
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / microbiology
  • Inflammation / pathology
  • Lactoferrin / pharmacology
  • Lactoferrin / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Stomach / immunology
  • Stomach / microbiology
  • Stomach / pathology

Substances

  • Anti-Bacterial Agents
  • LTF protein, human
  • Recombinant Proteins
  • Lactoferrin