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: Hai-Lun Sun, Mei-Ling Peng, Shiuan-Shinn Lee, Chun-Jung Chen, Wen-Ying Chen, Ming-Ling Yang, Yu-Hsiang Kuan
• Journal: Environmental toxicology (Environ Toxicol) Vol. 31 Issue 12 Pg. 1700-1709 (Dec 2016) ISSN: 1522-7278 [Electronic] United States
• PMID: 26213241 (Publication Type: Journal Article)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• Flavanones
• Hypoxia-Inducible Factor 1, alpha Subunit
• Interleukin-1beta
• Lipopolysaccharides
• NF-kappa B
• Neuroprotective Agents
• Tumor Necrosis Factor-alpha
• Catalase
• Glutathione Peroxidase
• Superoxide Dismutase
• wogonin

Topics

• Acute Lung Injury (metabolism, prevention & control)
• Animals
• Catalase (metabolism)
• Flavanones (pharmacology, therapeutic use)
• Glutathione Peroxidase (metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors, metabolism)
• Interleukin-1beta (metabolism)
• Lipid Peroxidation
• Lipopolysaccharides (pharmacology)
• Lung (drug effects, pathology)
• Male
• Mice, Inbred ICR
• NF-kappa B (metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Oxidative Stress (drug effects)
• Superoxide Dismutase (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation