title: Curcumin attenuates quinocetone induced apoptosis and inflammation via the opposite modulation of Nrf2/HO-1 and NF-kB pathway in human hepatocyte L02 cells.
abstract: The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 μM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress, mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor -kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX, a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway.
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, PR China.
authors.forename: Chongshan
authors.initials: C
authors.lastname: Dai
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, PR China.
authors.forename: Daowen
authors.initials: D
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, PR China.
authors.forename: Shen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, PR China. Electronic address: xiaoxl@cau.edu.cn.
authors.forename: Xilong
authors.initials: X
authors.lastname: Xiao
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, PR China. Electronic address: tssfj@163.com.
authors.forename: Shusheng
authors.initials: S
authors.lastname: Tang
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011810:Quinoxalines / Q000009:adverse effects*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D011810:Quinoxalines; D012333:RNA, Messenger; C502851:quinocetone; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D003474:Curcumin
keywords: Apoptosis; Curcumin; Inflammatory response; NF-kB pathway; Nrf2/HO-1 pathway; Quinocetone