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

Guo, Xiaochun, Chen, Liang, Chen, Jun, Xie, Ping, Li, Shangchun, He, Jun, Li, Wei, Fan, Huihui, Yu, Dezhao, Zeng, Cheng
Environmental science and pollution research international 2015 v.22 no.23 pp. 19273-19284
Cyanobacteria, antioxidants, glutathione, hepatotoxicity, lethal dose 50, liver, metabolism, metabolites, microcystin-LR, rats
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.