Nrf2/ARE信号通路在槲皮素抑制异烟肼诱导的肝细胞线粒体氧化损伤中的作用

doi:10.3969/j.issn.1004-616x.2021.03.009

Abstract

Abstract: OBJECTIVE： To investigate the role of the Nrf2/ARE signaling pathway on inhibitory effect of quercetin on mitochondrial oxidative damage which was induced by isoniazid (INH) in L- 02 hepatocytes. METHODS： L- 02 cells in cultures were randomly divided into several groups： negative control， INH (10 mmol/L)，quercetin alone (50 μmol/L) and combined (10 mmol/L INH+50 μmol/L quercetin). After cells were treated for 24 hours，cell viability was measured using the MTT method； levels of the mitochondrial reactive oxygen species (ROS) was detected by fluorescence probe DCFH-DA； contents of malondialdehyde (MDA)， glutathione (GSH) and the activity of superoxide dismutase (SOD) were measured using colorimetry to evaluate the oxidative damage status of mitochondria. In addition， the protein expressions of Nrf2 and HO-1 were detected using western blot analysis to assess changes in the Nrf2/ARE signaling pathway. RESULTS： Compared with the negative control group，cells from the INH group showed the followings：cell vitality was significantly decreased (P < 0.01)， mitochondrial ROS level and MDA content were significantly increased (P< 0.01)，GSH content and SOD activity were remarkable reduced (P < 0.01). Compared with the INH group，the other treated cells showed the followings： cell vitality was markedly increased (P < 0.01)， the level of mitochondrial ROS and the content of MDA were remarkable declined (P < 0.01)，the content of GSH and the activity of SOD were significantly elevated of the combined treatment group (P < 0.05 or P < 0.01). In addition， expressions of HO-1 protein in cytoplasm and Nrf2 protein in nucleus of the INH group were significantly higher than those in the negative control group (P < 0.01). Expressions of HO- 1 and Nrf2 proteins of the combined treatment group were markedly elevated compared with those of the INH group (P < 0.01). CONCLUSION： Quercetin inhibited mitochondrial oxidative damage which was induced by INH， and the mechanism might be mediated by quercetin-regulation of the Nrf2/ARE signaling pathway.

Key words: quercetin, isoniazid, Nrf2/ARE signaling pathway, mitochondrial, oxidative damage

CLC Number:

R965

CHEN Tingyu, CHEN Dayin, XIE Jinlu, GAO Xiren, LU Chunfeng. Role of the Nrf2/ARE signaling pathway on quercetin-inhibition of INH-induced mitochondrial oxidative damage in hepatocytes[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(3): 208-212,217.

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Role of the Nrf2/ARE signaling pathway on quercetin-inhibition of INH-induced mitochondrial oxidative damage in hepatocytes

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