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The role of GSH in microcystin‐induced apoptosis in rat liver: Involvement of oxidative stress and NF ‐κ B
Author(s) -
Chen Liang,
Li Shangchun,
Guo Xiaochun,
Xie Ping,
Chen Jun
Publication year - 2016
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22068
Subject(s) - oxidative stress , glutathione , buthionine sulfoximine , malondialdehyde , apoptosis , chemistry , glutathione reductase , glutathione peroxidase , microcystin lr , biochemistry , microbiology and biotechnology , pharmacology , catalase , biology , enzyme , cyanobacteria , bacteria , genetics
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 LD 50 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 LD 50 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 LD 50 but inhibited at 0.5 LD 50 . 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. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 552–560, 2016.