title: α-Lipoic acid protects against the oxidative stress and cytotoxicity induced by cadmium in HepG2 cells through regenerating glutathione regulated by glutamate-cysteine ligase.
abstract: Alpha-lipoic acid (α-LA) is an important antioxidant that is capable of regenerating other antioxidants, such as glutathione (GSH). In the present study, we examined the protective effects of α-LA against the oxidative stress and cytotoxicity induced by cadmium in human hepatoma cell lines (HepG2) and investigated if the process was mediated through regenerating GSH. Our results showed that after exposure to 25 μM cadmium for 16 h, there was a significant decrease in the cell viability and glutathione levels and a significant increase in lipid peroxidation (p<0.01) compared with untreated cells. The presence of α-LA significantly attenuated cadmium-induced cytotoxicity and lipid peroxidation, and reversed cellular GSH levels compared with cadmium-treated cells (p<0.05). Compared with the cells treated with cadmium, co-treatment with α-LA and cadmium significantly increased the activities of γ-glutamylcysteine ligase (γ-GCL), the rate limiting enzyme in GSH biosynthesis and the mRNA and the protein levels of γ-GCL catalytic subunit (GCLC) and a modifier subunit (GCLM). In conclusion, our results indicated that α-LA is an effective agent to reduce the oxidative stress and cytotoxicity induced by cadmium by regenerating GSH levels through increasing the activities and the expressions of γ-GCL.
authors.affiliation: a Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubating), Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: a Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubating), Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.affiliation: a Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubating), Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , PR China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Shi
authors.affiliation: a Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubating), Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , PR China.
authors.forename: Jiachun
authors.initials: J
authors.lastname: Wang
authors.affiliation: a Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubating), Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , PR China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000975:Antioxidants / Q000378:metabolism* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002104:Cadmium / Q000737:chemistry / Q000633:toxicity*; D002105:Cadmium Poisoning / Q000178:diet therapy / Q000201:enzymology / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D019587:Dietary Supplements; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D008063:Thioctic Acid / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D012333:RNA, Messenger; D002104:Cadmium; D008063:Thioctic Acid; C000609392:GCLC protein, human; C546365:GCLM protein, human; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione
keywords: Alpha-lipoic acid; antioxidant; cadmium; glutathione; oxidative stress; γ-glutamylcysteine ligase