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Niacin and Selenium Attenuate Sepsis-Induced Lung Injury by Up-Regulating Nuclear Factor Erythroid 2-Related Factor 2 Signaling. : 26646455

Cited 18 time in Web of Science Cited 19 time in Scopus
Authors

Kwon, Woon Yong; Suh, Gil Joon; Kim, Kyung Su; Jung, Yoon Sun; Kim, Sung Hee; Kim, Jae Seong; You, Kyoung Min

Issue Date
2016-06
Publisher
LIPPINCOTT WILLIAMS & WILKINS
Citation
Critical Care Medicine, Vol.44 No.6, pp. 370-382
Keywords
Niacin and Selenium Attenuate Sepsis-Induced Lung Injury by Up-Regulating Nuclear Factor Erythroid 2-Related Factor 2 Signaling.의약학glutathionelung injurynuclear factor erythroid 2–related factor 2nuclear factor κBreactive oxygen speciessepsis
Abstract
OBJECTIVES:To determine whether the combination therapy of niacin and selenium attenuates lung injury and improves survival during sepsis in rats and whether its benefits are associated with the activation of the glutathione redox cycle and up-regulation of nuclear factor erythroid 2-related factor 2.DESIGN:Prospective laboratory study.SETTING:University laboratory.SUBJECTS:Human lung microvascular endothelial cells and male Sprague-Dawley rats (n = 291).INTERVENTION:In lipopolysaccharide-exposed cells, the dose-related effects of niacin and selenium were assessed, and the therapeutic effects of the combination therapy of niacin (0.9 mM) and selenium (1.5 μM) were evaluated. The role of nuclear factor erythroid 2-related factor 2 was determined using nuclear factor erythroid 2-related factor 2 knockdown cells. In endotoxemic and cecal ligation and puncture with antibiotics rats, the therapeutic effects of the posttreatments of clinically relevant doses of niacin (360 mg/kg) and selenium (60 μg/kg) were evaluated.MEASUREMENTS AND MAIN RESULTS:Combination therapy reduced the hydrogen peroxide level via the synergistic activation of the glutathione redox cycle, which involves niacin-induced increases in glutathione reductase activity, and reduced the glutathione level and a selenium-induced increase in glutathione peroxidase activity. Combination therapy contributed to the up-regulation of nuclear factor erythroid 2-related factor 2, enhancement of glutathione synthesis, and down-regulation of nuclear factor κB signaling, but nuclear factor erythroid 2-related factor 2 knockdown inhibited the enhancement of glutathione synthesis and down-regulation of the nuclear factor κB pathway. The therapeutic effects of combination therapy on endotoxemic rats were consistent with those on lipopolysaccharide-exposed cells. In addition, the posttreatment of combination therapy attenuated lung injury and improved survival in endotoxemic and cecal ligation and puncture with antibiotics rats. However, individual therapies of niacin or selenium failed to achieve these benefits.CONCLUSIONS:The combination therapy of niacin and selenium attenuated lung injury and improved survival during sepsis. Its therapeutic benefits were associated with the synergistic activation of the glutathione redox cycle, reduction of hydrogen peroxide level, and up-regulation of nuclear factor erythroid 2-related factor 2.
ISSN
0090-3493
Language
English
URI
https://hdl.handle.net/10371/116988
DOI
https://doi.org/10.1097/CCM.0000000000001422
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College of Medicine/School of Medicine (의과대학/대학원)Emergency Medicine (응급의학전공)Journal Papers (저널논문_응급의학전공)
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