title: The role of GSH in microcystin-induced apoptosis in rat liver: Involvement of oxidative stress and NF-κB.
abstract: Microcystins (MCs) are potent and specific hepatotoxins produced by cyanobacteria in eutrophic waters, representing a health hazard to animals and humans. The objectives of this study are to determine the relationship between oxidative stress and NF-κB activity in MC-induced apoptosis in rat liver and the role of glutathione (GSH). Sprague-Dawley rats were intraperitoneally (i.p.) injected with microcystin-LR (MC-LR) at 0.25 and 0.5 LD50 with or without pretreatment of buthionine-(S,R)-sulfoximine (BSO), a specific GSH synthesis inhibitor. MC-LR induced time-dependent alterations of GSH levels in rat liver. Increased malondialdehyde (MDA) and significant changes of antioxidant enzymes including GSH peroxidase (GPX) and GSH reductase (GR) were also observed, particularly at 24 h post-exposure. The results indicated that acute exposure to MC-LR induced oxidative stress, and GSH depletion (BSO pretreatment) enhanced the level of oxidative stress. Furthermore, the modulation of pro-apoptotic gene p53 and Bax and anti-apoptotic gene Bcl-2 was observed in 0.5 LD50 group at 24 h, and the alteration was more pronounced by BSO injection before MC-LR treatment, suggesting that GSH played a protective role against MC-induced toxicity. Additionally, electrophoretic mobility shift assay (EMSA) showed that NF-κB was induced at 0.25 LD50 but inhibited at 0.5 LD50 . The above results indicated that the possible crosstalk of oxidative stress and NF-κB activity was associated with MC-LR-induced hepatocytes apoptosis in vivo. Our data will provide a new perspective for understanding the mechanisms of MC-induced liver injury.
authors.affiliation: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Shangchun
authors.initials: S
authors.lastname: Li
authors.affiliation: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.|College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Guo
authors.affiliation: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.affiliation: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D000458:Cyanobacteria / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D052998:Microcystins / Q000633:toxicity*; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D052998:Microcystins; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; C078588:microcystin; D004247:DNA; D005982:Glutathione Transferase; D005978:Glutathione
keywords: NF-κB; apoptosis; glutathione; liver; microcystin-LR; oxidative stress