HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Redox-active protein thioredoxin-1 administration ameliorates influenza A virus (H1N1)-induced acute lung injury in mice.

AbstractOBJECTIVES:
Influenza virus infections can cause severe acute lung injury leading to significant morbidity and mortality. Thioredoxin-1 is a redox-active defensive protein induced in response to stress conditions. Animal experiments have revealed that thioredoxin-1 has protective effects against various severe disorders. This study was undertaken to evaluate the protective effects of recombinant human thioredoxin-1 administration on influenza A virus (H1N1)-induced acute lung injury in mice.
DESIGN:
Prospective animal trial.
SETTING:
Research laboratory.
SUBJECTS:
Nine-week-old male C57BL/6 mice inoculated with H1N1.
INTERVENTION:
The mice were divided into a vehicle-treated group and recombinant human thioredoxin-1-treated group. For survival rate analysis, the vehicle or recombinant human thioredoxin-1 was administered intraperitoneally every second day from day -1 to day 13. For lung lavage and pathological analyses, vehicle or recombinant human thioredoxin-1 was administered intraperitoneally on days -1, 1, and 3.
MEASUREMENTS AND MAIN RESULTS:
Lung lavage and pathological analyses were performed at 24, 72, and 120 hrs after inoculation. The recombinant human thioredoxin-1 treatment significantly improved the survival rate of H1N1-inoculated mice, although the treatment did not affect virus propagation in the lung. The treatment significantly attenuated the histological changes and neutrophil infiltration in the lung of H1N1-inoculated mice. The treatment significantly attenuated the production of tumor necrosis factor-α and chemokine (C-X-C motif) ligand 1 in the lung and oxidative stress enhancement, which were observed in H1N1-inoculated mice. H1N1 induced expressions of tumor necrosis factor-α and chemokine (C-X-C motif) ligand 1 in murine lung epithelial cells MLE-12, which were inhibited by the addition of recombinant human thioredoxin-1. The recombinant human thioredoxin-1 treatment started 30 mins after H1N1 inoculation also significantly improved the survival of the mice.
CONCLUSIONS:
Exogenous administration of recombinant human thioredoxin-1 significantly improved the survival rate and attenuated lung histological changes in the murine model of influenza pneumonia. The protective mechanism of thioredoxin-1 might be explained by its potent antioxidative and anti-inflammatory actions. Consequently, recombinant human thioredoxin-1 might be a possible pharmacological strategy for severe influenza virus infection in humans.
AuthorsMasato Yashiro, Hirokazu Tsukahara, Akihiro Matsukawa, Mutsuko Yamada, Yosuke Fujii, Yoshiharu Nagaoka, Mitsuru Tsuge, Nobuko Yamashita, Toshihiro Ito, Masao Yamada, Hiroshi Masutani, Junji Yodoi, Tsuneo Morishima
JournalCritical care medicine (Crit Care Med) Vol. 41 Issue 1 Pg. 171-81 (Jan 2013) ISSN: 1530-0293 [Electronic] United States
PMID23222257 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antioxidants
  • Chemokine CXCL1
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Thioredoxins
Topics
  • Acute Lung Injury (drug therapy, immunology, pathology, virology)
  • Animals
  • Antioxidants (pharmacology, therapeutic use)
  • Chemokine CXCL1 (drug effects, metabolism)
  • Humans
  • Influenza A Virus, H1N1 Subtype
  • Influenza, Human (drug therapy)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophil Infiltration (drug effects)
  • Pneumonia, Viral (drug therapy)
  • Prospective Studies
  • Recombinant Proteins (pharmacology, therapeutic use)
  • Survival Analysis
  • Thioredoxins (pharmacology, therapeutic use)
  • Tumor Necrosis Factor-alpha (drug effects, metabolism)
  • Viral Load (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: