Quantitatively evaluating detoxification of the hepatotoxic microcystin-LR through the glutathione (GSH) pathway in SD 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.
College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.|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.
Xiaochun
X
Guo
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.|University of Chinese Academy of Sciences, Beijing, 100049, China.
Liang
L
Chen
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.
Jun
J
Chen
College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, Hubei, China. xieping@ihb.ac.cn.|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.
Ping
P
Xie
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.|University of Chinese Academy of Sciences, Beijing, 100049, China.
Shangchun
S
Li
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.
Jun
J
He
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.|University of Chinese Academy of Sciences, Beijing, 100049, China.
Wei
W
Li
College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.|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.
Huihui
H
Fan
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.|University of Chinese Academy of Sciences, Beijing, 100049, China.
Dezhao
D
Yu
College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.|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.
Cheng
C
Zeng
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism*; D008658:Inactivation, Metabolic; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008387:Marine Toxins; D052998:Microcystins / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014874:Water Pollutants, Chemical / Q000493:pharmacokinetics* / Q000633:toxicity
D008387:Marine Toxins; D052998:Microcystins; D014874:Water Pollutants, Chemical; C057862:cyanoginosin LR; D005978:Glutathione
Detoxification; GSH pathway; Liver; Microcystin-LR-GSH/Cys; Rat