title: Oligomeric proanthocyanidins alleviate hexabromocyclododecane-induced cytotoxicity in HepG2 cells through regulation on ROS formation and mitochondrial pathway.
abstract: Hexabromocyclododecane (HBCD), a type of brominated flame retardants (BFR), has become ubiquitous organic contaminants in recent years. However, studies on HBCD toxicity and the related molecular mechanisms are so far limited. The objective of the present study was to investigate the effects of oligomeric proanthocyanidins (OPCs) on cytotoxicity induced by HBCD and the underlying molecular mechanisms. HepG2 cells were treated with HBCD and/or OPCs at different concentrations, and cell viability, cell apoptosis, reactive oxygen species (ROS) production, cellular Ca(2+) level, mitochondrial membrane potential (ΔΨ), cytochrome C (Cyt-c) release, and nuclear factor-erythroid 2-related factor 2 (Nrf2) proteins expression were evaluated. Results showed that HBCD induced toxic effects in HepG2 cells in a concentration-dependent manner. HBCD at high concentrations (40 and 60μM) caused a significant decrease of cell viability and led to elevated cell apoptosis ratio, intracellular Ca(2+) level, cytoplasmic Cyt-c level, and ROS production, together with a loss of ΔΨ and mobilization of Nrf2. Pretreatment with OPCs effectively attenuated the cytotoxic effects and ROS production, as well as mitochondrial responses induced by HBCD. Thus, OPCs could alleviate cytotoxicity in HepG2 cells induced by HBCD through regulation on intracellular Ca(2+) level and ROS formation in a mitochondrial pathway.
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China. Electronic address: peace74839@shu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: An
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.
authors.forename: Cen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, PR China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism; D005411:Flame Retardants / Q000633:toxicity*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000037:antagonists & inhibitors / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis; D044945:Proanthocyanidins / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D027843:Vitis / Q000737:chemistry
chemical_list: D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; C089796:hexabromocyclododecane; D045304:Cytochromes c; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D002118:Calcium
keywords: Cyt-c; HBCD; Mitochondrial membrane potential; Nrf2; OPCs; ROS