title: 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.affiliation: Department of Anesthesia, YanTai Yu Huang Ding Hospital, YanTai city, ShanDong Province 264000, China. Electronic address: hzhongma520@yeah.net.
authors.forename: Hongzhong
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Pathology, YanTai Yu Huang Ding Hospital, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Anesthesia, YanTai Yu Huang Ding Hospital, YanTai city, ShanDong Province 264000, China.
authors.forename: Suchun
authors.initials: S
authors.lastname: Ding
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006569:Hesperidin / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D047495:PPAR gamma / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism*; D055397:Ventilator-Induced Lung Injury / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D016207:Cytokines; D047495:PPAR gamma; D051996:Transcription Factor RelA; D006569:Hesperidin; D009195:Peroxidase; C013015:hesperetin
keywords: Hesperetin; Inflammation; NF-κB pathway; PPAR-γ; Ventilator-induced ALI