title: The role of glutathione detoxification pathway in MCLR-induced hepatotoxicity in SD rats.
abstract: In the present study, we investigated the role of glutathione (GSH) and its related enzymes in Sprague Dawley (SD) rats subjected to microcystin-leucine-arginine (MCLR)-induced hepatotoxicity. SD rats were intraperitoneally (i.p.) injected with MCLR after pretreating with or without buthionine-(S,R)-sulfoximine (BSO), an inhibitor of GSH synthesis. The depletion of GSH with BSO enhanced MCLR-induced oxidative stress, resulting in more severe liver damage and higher MCLR accumulation. Similarly, the contents of malondialdehyde (MDA), total GSH (T-GSH), oxidized GSH (GSSG) and GSH were significantly enhanced in BSO pretreated rats following MCLR treatment. The study showed that the transcription of GSH-related enzymes such as glutathione-S-transferase (GST), γ-glutamylcysteine synthetase (γ-GCS), glutathione reductase (GR) varied in different ways (expect for glutathione peroxidase (GPx), whose gene expression was induced in all treated groups) with or without BSO pretreatment before MCLR exposure, suggesting an adaptative response of GSH-related enzymes at transcription level to combat enhancement of oxidative stress induced by MCLR when pretreated with BSO. These data suggested the tissues with low GSH concentration are highly vulnerable to MCLR toxicity and GSH was critical for the detoxification in MCLR-induced hepatotoxicity in vivo.
authors: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China.|University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
authors: Shangchun
authors: S
authors: Li
authors: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China.
authors: Jun
authors: J
authors: Chen
authors: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China.
authors: Ping
authors: P
authors: Xie
authors: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China.|Fisheries College, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
authors: Xiaochun
authors: X
authors: Guo
authors: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China.|Fisheries College, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
authors: Huihui
authors: H
authors: Fan
authors: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China.|University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
authors: Dezhao
authors: D
authors: Yu
authors: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China.|Fisheries College, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
authors: Cheng
authors: C
authors: Zeng
authors: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China.|University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
authors: Liang
authors: L
authors: Chen
mesh_terms: D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008387:Marine Toxins; D052998:Microcystins / Q000737:chemistry / Q000633:toxicity*; D008854:Microscopy, Electron; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D012333:RNA, Messenger; D008315:Malondialdehyde; D019328:Buthionine Sulfoximine; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; C057862:cyanoginosin LR; D005978:Glutathione
keywords: BSO; SD rat; glutathione; liver; microcystin-LR; oxidative stress