title: Prevention of hypoglycemia-induced hippocampal neuronal death by N-acetyl-L-cysteine (NAC).
abstract: Type 1 and type 2 diabetic patients who are treated with insulin or other blood glucose reducing agents for tight control of blood glucose levels are frequently at risk of experiencing severe hypoglycemia which can lead to seizures, loss of consciousness and death. Hypoglycemic neuronal cell death is not a simple result of low glucose supply to the brain, but, instead, results from a cell death signaling pathway that is started by the re-administration of glucose after glucose deprivation. Zinc is a biologically important element for physiological function of central nervous system. However, excessive zinc release from the presynaptic terminals and subsequent translocation into the postsynaptic neurons may contribute to neuronal death following hypoglycemia. N-acetyl-L-cysteine (NAC) acts as a zinc chelator that alleviates zinc-induced neuronal death processes. In addition, NAC restores levels of neuronal glutathione (GSH), a potent antioxidant, by providing a cell-permeable source of cysteine. Thus, we hypothesized that NAC treatment can reduce neuronal cell death, not only by increasing GSH concentration but also by zinc chelation. As a result, we found that NAC decreased the oxidative stress, zinc release and translocation, and improved the level of glutathione. Therefore, NAC administration alleviated hippocampal neuron death in hypoglycemia-induced rats.
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Korea.
authors.forename: A Ra
authors.initials: AR
authors.lastname: Kho
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Korea.
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Choi
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Korea.
authors.forename: Song Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Korea.
authors.forename: Dae Ki
authors.initials: DK
authors.lastname: Hong
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Korea.
authors.forename: Sang Hwon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Neurology, College of Medicine, Hallym University, Chuncheon, Korea.
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Nursing, Inha University, Incheon, Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Sohn
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Korea. swsuh@hallym.ac.kr.
authors.forename: Sang Won
authors.identifier: http://orcid.org/0000-0002-7492-579X
authors.initials: SW
authors.lastname: Suh
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D007003:Hypoglycemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D017628:Microglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000378:metabolism
chemical_list: D005978:Glutathione; D015032:Zinc; D000111:Acetylcysteine
keywords: Glutathione; Hippocampus; Hypoglycemia; N-acetyl-L-cysteine; Neuron death; Zinc