期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 308, 期 -, 页码 91-101出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2016.07.006
关键词
Realgar; Glutathione; System X-AG(-); System X-C(-); MRP-1; Nrf2
资金
- National Natural Science Foundation of China [81473417]
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 X-AG(-), system X-C(-), multidrug resistance-associated protein 1 (MRP-1), nuclear factor E2-related factor 2 (Nrf2), gamma-glutamylcysteinesynthetase (gamma-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. (C) 2016 Elsevier Inc. All rights reserved.
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