title: Effects of realgar on GSH synthesis in the mouse hippocampus: Involvement of system XAG(-), system XC(-), MRP-1 and Nrf2.
abstract: Realgar is a type of mineral drug that contains arsenic and has neurotoxicity. Glutathione (GSH), which is the main antioxidant in the central nervous system, plays a key role in antioxidant defenses and the detoxification of arsenic. However, whether realgar interferes with the synthesis of GSH in the brain and the molecular mechanisms underlying its effects are largely unknown. Here, we used mouse models of exposure to realgar to show that realgar affects the synthesis of GSH in the hippocampus, leading to ultrastructural changes in hippocampal neurons and synapses and deficiencies in cognitive abilities, and that the mechanisms that cause this effect may be associated with alterations in the expression of system XAG(-), system XC(-), multidrug resistance-associated protein 1(MRP-1), nuclear factor E2-related factor 2 (Nrf2), γ-glutamylcysteine synthetase (γ-GCS), and the levels of glutamate (Glu) and cysteine (Cys) in the extracellular fluid. These findings provide a theoretical basis for preventing the drug-induced chronic arsenic poisoning in the nervous system that is triggered by realgar.
authors.affiliation: Department of Health Laboratory Technology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, People's Republic of China; School of Basic Medical Sciences, North China University of Science and Technology, 46 Xinhua Road, Tangshan, Hebei 063009, People's Republic of China.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Health Laboratory Technology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, People's Republic of China.
authors.forename: Mo
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Health Laboratory Technology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, People's Republic of China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Health Laboratory Technology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, People's Republic of China.
authors.forename: Taoguang
authors.initials: T
authors.lastname: Huo
authors.affiliation: Department of Health Laboratory Technology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, People's Republic of China; School of Pharmacy, Liaoning University of Traditional Chinese Medicine, No. 77 Shenning1 Road, Double D Port, Dalian, Liaoning 116600, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Health Laboratory Technology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, People's Republic of China.
authors.forename: Xuexin
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Department of Health Laboratory Technology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, People's Republic of China; School of Pharmacy, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, People's Republic of China.
authors.forename: Mingmei
authors.initials: M
authors.lastname: Yuan
authors.affiliation: Department of Health Laboratory Technology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, People's Republic of China. Electronic address: jianghong@mail.cmu.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001152:Arsenicals; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000096:biosynthesis*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013440:Sulfides / Q000633:toxicity*
chemical_list: D001152:Arsenicals; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D051267:NF-E2-Related Factor 2; D012333:RNA, Messenger; D013440:Sulfides; C495636:Nfe2l2 protein, mouse; C058317:arsenic disulfide; C421109:multidrug resistance-associated protein 1
keywords: Glutathione; MRP-1; Nrf2; Realgar; System X(AG)(−); System X(C)(−)