标题:S-allylmercaptocysteine ameliorates lipopolysaccharide-induced acute lung injury in mice by inhibiting inflammation and oxidative stress via nuclear factor kappa B and Keap1/Nrf2 pathways
作者:Mo M.; Li S.; Dong Z.; Li C.; Sun Y.; Li A.; Zhao Z.
作者机构:[Mo, M] School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, China, Shandong Key University Laborator 更多
通讯作者:Zhao, Z(zxzhao@sdu.edu.cn)
通讯作者地址:[Zhao, Z] School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, China;
来源:International Immunopharmacology
出版年:2020
卷:81
DOI:10.1016/j.intimp.2020.106273
关键词:Acute lung injury; Inflammation; Keap1/Nrf2; nuclear factor-κB (NF-κB); Oxidative stress; S-allylmercaptocysteine
摘要:The garlic-derived organosulfur compound S-allylmercaptocysteine (SAMC) has been reported to exhibit anti-inflammatory and anti-oxidative activities, whereas its potential therapeutic effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) is unknown. In this study, we focused on exploring the therapeutic effects of SAMC on LPS-induced ALI mice and the involvement of underlying molecular mechanisms. BalB/c mice were treated with SAMC (10, 30 and 60 mg/kg) or positive control N-acetylcysteine (NAC, 500 mg/kg) by gavage after intratracheal instillation of LPS for 30 min and were sacrificed 24 h after LPS administration. Our results indicate that the treatment with SAMC not only ameliorated the histological changes but also decreased LPS-triggered lung edema. Moreover, SAMC displayed an anti-inflammatory effect through reducing inflammatory cells infiltration, myeloperoxidase (MPO) formation and inhibiting pro-inflammatory cytokines/mediator production including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) via suppressing the activation of nuclear factor-kappaB (NF-κB) signaling pathway. Furthermore, SAMC attenuated oxidative stress evoked by LPS via diminishing malondialdehyde (MDA) formation and reversing glutathione (GSH) and superoxide dismutase (SOD) depletion. Meanwhile, SAMC up-regulated expressions of endogenous antioxidant/detoxifying proteins including heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1(NQO1) through reversing the suppression of Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway. Our results demonstrate that SAMC effectively attenuated LPS-induced ALI which was largely dependent upon inhibition of inflammation and oxidative stress via NF-κB and Keap1/Nrf2 signaling pathways. © 2020 Elsevier B.V.
收录类别:SCOPUS
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079417569&doi=10.1016%2fj.intimp.2020.106273&partnerID=40&md5=d38bc769231705f6c9eb264c1a6c46d5
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