Dexmedetomidine alleviates hepatic injury via the inhibition of oxidative stress and activation of the Nrf2/HO-1 signaling pathway

被引:44
作者
Zhao, Yuan [1 ]
Kong, Gao-Yin [1 ]
Pei, Wan-Min [1 ]
Zhou, Bo [1 ]
Zhang, Qin-Qin [1 ]
Pan, Bing-Bing [1 ]
机构
[1] Hunan Normal Univ, Hunan Prov Peoples Hosp, Clin Res Ctr Anesthesiol ERAS Hunan Prov, Dept Anesthesia,Affiliated Hosp 1, 61 West Jiefang Rd, Changsha 410005, Hunan, Peoples R China
关键词
Dexmedetomidine; hepatic injury; inflammation; oxidative stress; Nrf2; HO-1 signaling pathway; ISCHEMIA-REPERFUSION INJURY; ACUTE LUNG INJURY; LIVER-INJURY; RAT MODEL; PROTECTS; MANAGEMENT;
D O I
10.1684/ecn.2019.0431
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Dexmedetomidine (Dex), frequently used as an effective sedative, was reported to play a critical role in the protection of multiple organs. However, its underlying mechanism of a putative protective effect on ischemia/reperfusion (I/R)-induced liver injury is still unclear. Methods: A hepatocyte injury model was established by treating WRL-68 cells with oxygen and glucose deprivation/reoxygenation (OGD/R). Enzyme Linked Immunosorbent Assay (ELISA) kits were used to determine the level of inflammatory factors (IL-6, IL-1 beta, and TNF-alpha), and oxidative stress indicators (ROS, MDA, GSH-Px, and SOD). MTT assay and flow cytometry analysis were used to determine the influence of Dex on cell viability and cell apoptosis. Expression of nuclear factor erythroid-derived 2- like 2 (Nrf2), HO-1, and apoptosis-related proteins (Bax, Bcl-2, caspase3, and caspase9) were detected by qRT-PCR and western blotting. Results: Dex promoted cell viability and suppressed cell apoptosis in OGD/R-treated WRL-68 cells. Dex reduced TNF-alpha, IL-6, IL-1 beta, ROS, and MDA production, whereas it increased that of SOD and GSH-Px in OGD/R-treated WRL-68 cells. Moreover, Nrf2, HO-1, and Bcl-2 expression was upregulated, whereas, in contrast, transcripts for Bax, caspase3, and caspase9 were downregulated following Dex treatment under OGD/R. Knockdown of Nrf2 reversed the Dex effects on cell proliferation, apoptosis, and expression of TNF-alpha, IL-6, IL-1 beta, ROS, MDA, SOD, and GSH-Px. Conclusion: Dex protects WRL-68 cells against OGD/R-induced injury by inhibiting inflammation, oxidative stress, and cell apoptosis via the activation of Nrf2/HO-1 signaling pathway, suggesting that Dex may be a potential protector against hepatic injury.
引用
收藏
页码:88 / 97
页数:10
相关论文
共 32 条
  • [1] Different doses of dexmedetomidine reduce plasma cytokine production, brain oxidative injury, PARP and caspase expression levels but increase liver oxidative toxicity in cerebral ischemia-induced rats
    Akpinar, Orhan
    Naziroglu, Mustafa
    Akpinar, Hatice
    [J]. BRAIN RESEARCH BULLETIN, 2017, 130 : 1 - 9
  • [2] [Anonymous], 2018, PHARMACOTHERAPY, V38, pe29, DOI 10. 1002/phar. 2101
  • [3] [Anonymous], 2018, LANCET ONCOL, V19, pe581
  • [4] [Anonymous], 2018, PHARMACEUTICALS BASE, V11
  • [5] Dexmedetomidine (DEX) protects against hepatic ischemia/reperfusion (I/R) injury by suppressing inflammation and oxidative stress in NLRC5 deficient mice
    Chen, Zong
    Ding, Tao
    Ma, Chuan-Gen
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2017, 493 (02) : 1143 - 1150
  • [6] National trends in pediatric blunt spleen and liver injury management and potential benefits of an abbreviated bed rest protocol
    Dodgion, Christopher M.
    Gosain, Ankush
    Rogers, Andrew
    St Peter, Shawn D.
    Nichol, Peter F.
    Ostlie, Daniel J.
    [J]. JOURNAL OF PEDIATRIC SURGERY, 2014, 49 (06) : 1004 - 1008
  • [7] Protective effect of Anwulignan against D-galactose-induced hepatic injury through activating p38 MAPK-Nrf2-HO-I pathway in mice
    Gao, Jiaqi
    Yu, Zepeng
    Jing, Shu
    Jiang, Weihai
    Liu, Cong
    Yu, Chunyan
    Sun, Jinghui
    Wang, Chunmei
    Chen, Jianguang
    Li, He
    [J]. CLINICAL INTERVENTIONS IN AGING, 2018, 13 : 1859 - 1869
  • [8] Dexmedetomidine
    Gerresheim, G.
    Schwemmer, U.
    [J]. ANAESTHESIST, 2013, 62 (08): : 661 - 672
  • [9] Protective effect of dexmedetomidine in a rat model of α-naphthylthioureae-induced acute lung injury
    Hanci, Volkan
    Yurdakan, Gamze
    Yurtlu, Serhan
    Turan, Isil Ozkocak
    Sipahi, Emine Yilmaz
    [J]. JOURNAL OF SURGICAL RESEARCH, 2012, 178 (01) : 424 - 430
  • [10] Huang Jinglan, 2017, Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi, V31, P751, DOI 10.7507/1002-1892.201701104