Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 69, Issue -, Pages 249-257Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2014.01.028
Keywords
Rutin; Acute lung injury; Lipopolysaccharide; SOD; CAT; GPx; HO-1; NF-kappa B; MAPK; Free radicals
Funding
- National Science Council of the Republic of China, Taiwan [NSC102-2320-B-040-009]
- Show Chwan Health Care System of the Republic of China, Taiwan [RD101060]
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Acute lung injury (ALI) is a serious disease with unacceptably high mortality and morbidity rates. Up to now, no effective therapeutic strategy for ALI has been established. Rutin, quercetin-3-rhamnosyl glucoside, expresses a wide range of biological activities and pharmacological effects, such as anti-inflammatory, antihypertensive, anticarcinogenic, vasoprotective, and cardioprotective activities. Pretreatment with rutin inhibited not only histopathological changes in lung tissues but also infiltration of polymorphonuclear granulocytes into bronchoalveolar lavage fluid in lipopolysaccharide (LPS)-induced ALI. In addition, LPS-induced inflammatory responses, including increased secretion of proinflammatory cytokines and lipid peroxidation, were inhibited by rutin in a concentration-dependent manner. Furthermore, rutin suppressed phosphorylation of NF-kappa B and MAPK and degradation of I kappa B, an NF-kappa B inhibitor. Decreased activities of antioxidative enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase-1 caused by LPS were reversed by rutin. At the same time, we found that ALI amelioration by chelation of extracellular metal ions with rutin is more efficacious than with deferoxamine. These results indicate that the protective mechanism of rutin is through inhibition of MAPK-NF-kappa B activation and upregulation of antioxidative enzymes. (c) 2014 Elsevier Inc. All rights reserved.
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