Hesperetin attenuates ventilator-induced acute lung injury through inhibition of NF-κB-mediated inflammation.

Abstract

Hesperetin, a major bioflavonoid in sweet oranges and lemons, has been reported to have anti-inflammatory properties. However, the effect of hesperetin on ventilator-induced acute lung injury has not been studied. In present study, we investigated the protective effect of hesperetin on ventilator-induced acute lung injury in rats. Rats were orally administered hesperetin (10, 20, or 40mg/kg) two hour before acute lung injury was induced by mechanical ventilation. Rats were then randomly divided into six groups: the lung protective ventilation group (n=20, LV group), injurious ventilation group (n=20, HV group), vehicle-treated injurious ventilation group (n=20, LV+vehicle group), hesperetin (10mg/kg)-treated acute lung injury group (n=20, HV+Hsp (10mg)), hesperetin (20mg/kg)-treated acute lung injury group (n=20, HV+Hsp (20mg)), and hesperetin (40mg/kg)-treated acute lung injury group (n=20, HV+Hsp (40mg)). The lung tissues and bronchoalveolar lavage fluid were isolated for subsequent measurements. Treatment with hesperetin dramatically improved the histology of lung tissue, and reduced the wet/dry ratio, myeloperoxidase activity, protein concentration, and production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and MIP-2 in the bronchoalveolar lavage fluid of rats with ventilator-induced acute lung injury. Additionally, our study indicated that this protective effect of hesperetin results from its ability to increase the expression of peroxisome proliferator-activated receptor (PPAR)-γ and inhibit the activation of the nuclear factor (NF)-κB pathway. These results suggest that hesperetin may be a potential novel therapeutic candidate for protection against ventilator-induced acute lung injury.

• Authors: Hongzhong Ma, Xiaoli Feng, Suchun Ding
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 769 Pg. 333-41 (Dec 15 2015) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 26610718 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• PPAR gamma
• Transcription Factor RelA
• Hesperidin
• Peroxidase
• hesperetin

Topics

• Animals
• Bronchoalveolar Lavage Fluid
• Cell Survival (drug effects)
• Cytokines (biosynthesis, metabolism)
• Gene Expression Regulation (drug effects)
• Hesperidin (pharmacology, therapeutic use)
• Inflammation (metabolism)
• Lung (drug effects, immunology, metabolism, pathology)
• Macrophages (drug effects)
• Male
• PPAR gamma (metabolism)
• Peroxidase (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Transcription Factor RelA (metabolism)
• Ventilator-Induced Lung Injury (drug therapy, immunology, metabolism, pathology)