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 neuropr...

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Published in:Environmental toxicology 2016-12, Vol.31 (12), p.1700-1709
Main Authors: Sun, Hai-Lun, Peng, Mei-Ling, Lee, Shiuan-Shinn, Chen, Chun-Jung, Chen, Wen-Ying, Yang, Ming-Ling, Kuan, Yu-Hsiang
Format: Article
Language:English
Subjects:
5,7‐dihydroxy‐8‐methoxyflavone (DHMF)
7-dihydroxy-8-methoxyflavone (DHMF)
acute lung injury
Acute Lung Injury - metabolism
Acute Lung Injury - prevention & control
Animals
antioxidative enzymes
Catalase - metabolism
endotoxin
Flavanones - pharmacology
Flavanones - therapeutic use
Glutathione Peroxidase - metabolism
HIF-1α
Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Interleukin-1beta - metabolism
Lipid Peroxidation
Lipopolysaccharides - pharmacology
Lung - drug effects
Lung - pathology
Male
Mice, Inbred ICR
Neuroprotective Agents - pharmacology
Neuroprotective Agents - therapeutic use
NF-kappa B - metabolism
Oxidative Stress - drug effects
Superoxide Dismutase - metabolism
Tumor Necrosis Factor-alpha - metabolism
Up-Regulation
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Summary: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.
ISSN:1520-4081
1522-7278
DOI:10.1002/tox.22172