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Environ Sci Pollut Res Int. 2015 Dec;22(23):19273-84. doi: 10.1007/s11356-015-5531-2. Epub 2015 Oct 21.

Quantitatively evaluating detoxification of the hepatotoxic microcystin-LR through the glutathione (GSH) pathway in SD rats.

Guo X1,2, Chen L2,3, Chen J4, Xie P5,6, Li S2,3, He J2, Li W2,3, Fan H1,2, Yu D2,3, Zeng C1,2.

Author information

1
College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.
2
Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, Hubei, China.
3
University of Chinese Academy of Sciences, Beijing, 100049, China.
4
Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, Hubei, China. chenjun@ihb.ac.cn.
5
College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, Hubei, China. xieping@ihb.ac.cn.
6
Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, Hubei, China. xieping@ihb.ac.cn.

Abstract

Glutathione (GSH) plays crucial roles in antioxidant defense and detoxification metabolism of microcystin-LR (MC-LR). However, the detoxification process of MC-LR in mammals remains largely unknown. This paper, for the first time, quantitatively analyzes MC-LR and its GSH pathway metabolites (MC-LR-GSH and MC-LR-Cys) in the liver of Sprague-Dawley (SD) rat after MC-LR exposure. Rats received intraperitoneal (i.p.) injection of 0.25 and 0.5 lethal dose 50 (LD50) of MC-LR with or without pretreatment of buthionine-(S,R)-sulfoximine (BSO), an inhibitor of GSH synthesis. The contents of MC-LR-GSH were relatively low during the experiment; however, the ratio of MC-LR-Cys to MC-LR reached as high as 6.65 in 0.5 LD50 group. These results demonstrated that MC-LR-GSH could be converted to MC-LR-Cys efficiently, and this metabolic rule was in agreement with the data of aquatic animals previously reported. MC-LR contents were much higher in BSO + MC-LR-treated groups than in the single MC-LR-treated groups. Moreover, the ratio of MC-LR-Cys to MC-LR decreased significantly after BSO pretreatment, suggesting that the depletion of GSH induced by BSO reduced the detoxification of MCs. Moreover, MC-LR remarkably induced liver damage, and the effects were more pronounced in BSO pretreatment groups. In conclusion, this study verifies the role of GSH in the detoxification of MC-LR and furthers our understanding of the biochemical mechanism for SD rats to counteract toxic cyanobacteria.

KEYWORDS:

Detoxification; GSH pathway; Liver; Microcystin-LR-GSH/Cys; Rat

PMID:
26490924
DOI:
10.1007/s11356-015-5531-2
[Indexed for MEDLINE]

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