Curcumin attenuates quinocetone induced apoptosis and inflammation via the opposite modulation of Nrf2/HO-1 and NF-kB pathway in human hepatocyte L02 cells. (September 2016)

• Record Type: Journal Article
• Authors: Dai, Chongshan; Li, Bin; Zhou, Yan; Li, Daowen; Zhang, Shen; Li, Hui; Xiao, Xilong; Tang, Shusheng
• Is Part Of: Food and chemical toxicology. Volume 95(2016)
• Page Start: 52
• Page End: 63
• Publication Date: 2016-09
• Subjects: Curcumin -- Quinocetone -- Apoptosis -- Inflammatory response -- Nrf2/HO-1 pathway -- NF-kB pathway; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2016.06.025
• Languages: English
• ISSNs: 0278-6915

Abstract

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. Graphical abstract: Highlights: Mitochondrial apoptotic pathway and inflammatory response particulate in QCT induced cell death in L02 cell. Curcumin could effectively inhibit QCT induced iNOS/NO mediated inflammation via the inhibition of NF-kB pathway. Curcumin could effectively inhibit QCT induced mitochondrial apoptotic pathway via the activation of Nrf2/HO-1pathway. These foundings provide the important information for preventing QdNOs family members-induced cytotoxicity and apoptosis.