title: The protective role of 5-hydroxymethyl-2-furfural (5-HMF) against acute hypobaric hypoxia.
abstract: Our previous study showed that pretreatment with 5-hydroxymethyl-2-furfural (5-HMF) led to protection against hypoxic injury via a p-ERK-mediated pathway in vitro. Whether the protection of 5-HMF against hypoxia is effective in vivo is unknown. The present study is aimed to verify the role of 5-HMF in acute hypobaric hypoxia using Kunming mice as an in vivo model and further investigate the underlying mechanisms. Mice pretreated with or without 5-HMF for 1 h were exposed to acute hypobaric hypoxic condition for 6 h and then the survival time, the survival rate, the permeability of blood-brain barrier (BBB), the histological analysis in hippocampus and cortex, and the phosphorylation level of mitogen-activated protein kinases (ERK, JNK, and p38) were investigated. The results showed that 5-HMF significantly increased the survival time and the survival rate of mice. Accordingly, pretreatment with 5-HMF markedly attenuated acute hypobaric hypoxia-induced permeability of BBB (P < 0.01). In addition, the cellular damage extent of the hippocampus and the cortex induced by hypoxia for 6 h was also attenuated by pretreatment with 5-HMF, especially in the hippocampus CA1 region. Furthermore, the activation of ERK rather than JNK and p38 was involved in the protection of 5-HMF against acute hypobaric hypoxia. In summary, 5-HMF enhanced the survival capability of mice and decreased acute hypoxic damage to the brain, which may be associated with the effects on BBB and p-ERK.
authors.affiliation: Department of Neurobiology, Beijing Institute for Neuro-Science, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, People's Republic of China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Li
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Wu
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.forename: Kui-Wu
authors.initials: KW
authors.lastname: Wu
authors.forename: Lei
authors.initials: L
authors.lastname: Xiong
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Zhu
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
mesh_terms: D000531:Altitude; D000818:Animals; D001274:Atmospheric Pressure; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D015996:Survival Rate; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C008046:5-hydroxymethylfurfural; D005662:Furaldehyde; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases