title: Polychlorinated biphenyl quinone metabolites lead to oxidative stress in HepG2 cells and the protective role of dihydrolipoic acid.
abstract: Parent polychlorinated biphenyls (PCBs) have been shown to induce cellular oxidative stress. However, the effects of PCB active metabolites have not been extensively investigated. Parent PCBs are first converted to hydroquinone metabolites via cytochrome P-450-catalyzed hydroxylation, and the hydroquinone metabolites are then further oxidized into the corresponding quinone metabolites. Quinones are responsible for a wide range of toxic effects because of their high reactivity. Previous studies have suggested that reactive oxygen species (ROS) play important roles in multiple toxic mechanisms. In this context, the present study was undertaken to investigate oxidative stress resulting from treatment with PCB quinones in HepG2 cells. The protective effects resulting from co-administration of dihydrolipoic acid (DH-LA) were also investigated. We have found that exposure to PCB quinones leads to: (1) a decrease in cell viability; (2) an increase in both the total ROS production and superoxide production; (3) only 3Cl-PCBQ caused significant increase in the thiobarbituric acid reactive substances (TBARS) level; (4) an increase in SOD activity and a decrease in catalase activity; and (5) a decrease in GST activity and GSH level. We have also found that quinones possessing a higher number of chlorine atoms on the quinone ring display a greater activity and that DH-LA is an effective protective agent as it diminishes PCB quinone-induced cellular oxidative stress.
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analysis, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Erqun
authors.initials: E
authors.lastname: Song
authors.forename: Lichao
authors.initials: L
authors.lastname: Liu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ma
authors.forename: Xingguo
authors.initials: X
authors.lastname: Tian
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D054879:Halogenation; D056945:Hep G2 Cells; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D011809:Quinones / Q000378:metabolism / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004785:Environmental Pollutants; D011809:Quinones; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D011078:Polychlorinated Biphenyls; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione