title: Endotoxin-induced acute lung injury in mice is protected by 5,7-dihydroxy-8-methoxyflavone via inhibition of oxidative stress and HIF-1α.
abstract: Up to date, the morbidity and mortality rates of acute lung injury (ALI) still rank high among clinical illnesses. Endotoxin, also called lipopolysaccharide (LPS), induced sepsis is the major cause for ALI. Beneficial biological effects, such as antioxidation, anti-inflammation, and neuroprotection was found to express by 5,7-dihydroxy-8-methoxyflavone (DHMF). The purpose of present study was to investigate the potential protective effects of DHMF and the possibile mechanisms involved in LPS-induced ALI. In our experimental model, ALI was induced in mice by intratracheal injection of LPS, and DHMF at various concentrations was injected intraperitoneally for 30 min prior to LPS administration. Pretreatment with DHMF inhibited not only the histolopatholgical changes occurred in lungs but also leukocytes infiltration in LPS-induced ALI. Decreased activity of antioxidative enzymes (AOE) such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) caused by LPS was reversed by DHMF. LPS-induced lipid peroxidation HIF-1α accumulation, NF-κB phosphorylation, and IκBα degradation were all inhibited by DHMF. In addition, LPS-induced expression of proinflammatory mediators such as TNF-α and IL-1β were also inhibited by 5,7-dihydroxy-8-methoxyflavone. These results suggested that the protective mechanisms of DHMF on endotoxin-induced ALI might be via up-regulation of antioxidative enzymes, inhibition of NFκB phosphorylation, and HIF-1α accumulation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1700-1709, 2016.
authors.affiliation: Department of Pediatric, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Hai-Lun
authors.initials: HL
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, School of Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Peng
authors.affiliation: School of Public Health, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shiuan-Shinn
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Department of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Department of Anatomy, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Kuan
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D044950:Flavanones; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C085514:wogonin
keywords: 5,7-dihydroxy-8-methoxyflavone (DHMF); HIF-1α; acute lung injury; antioxidative enzymes; endotoxin