5-HMF attenuates striatum oxidative damage via Nrf2/ARE signaling pathway following transient global cerebral ischemia.
Recent studies have shown 5-hydroxymethyl-2-furfural (5-HMF) has favorable biological effects, and its neuroprotection in a variety of neurological diseases has been noted. Our previous study showed that treatment of 5-HMF led to protection against permanent global cerebral ischemia. However, the underlying mechanisms in cerebral ischemic injury are not fully understood. This study was conducted to investigate the neuroprotective effect of 5-HMF and elucidate the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway mechanism in the striatum after transient global cerebral ischemia. C57BL/6 mice were subjected to bilateral common carotid artery occlusion for 20 min and sacrificed 24 h after reperfusion. 5-HMF (12 mg/kg) or an equal volume of vehicle was intraperitoneally injected 30 min before ischemia and 5 min after the onset of reperfusion. At 24 h after reperfusion, neurological function was evaluated by neurological disability status scale, locomotor activity test and inclined beam walking test. Histological injury of the striatum was observed by cresyl violet staining and terminal deoxynucleotidyl transferase (TdT)-mediated dNTP nick end labeling (TUNEL) staining. Oxidative stress was evaluated by the carbonyl groups introduced into proteins, and malondialdehyde (MDA) levels. An enzyme-linked immunosorbent assay (ELISA)-based measurement was used to detect Nrf2 DNA binding activity. Nrf2 and its downstream ARE pathway protein expression such as heme oxygenase-1, NAD (P)H:quinone oxidoreductase 1, glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modulatory subunit were detected by western blot. Our results showed that 5-HMF treatment significantly ameliorated neurological deficits, reduced brain water content, attenuated striatum neuronal damage, decreased the carbonyl groups and MDA levels, and activated Nrf2/ARE signaling pathway. Taken together, these results demonstrated that 5-HMF exerted significant antioxidant and neuroprotective effects following transient cerebral ischemia, possibly through the activation of the Nrf2/ARE signaling pathway.
Department of Physiology, Jining Medical University, 16 He-hua Street, Bei-hu District, Jining, Shandong, 272067, People's Republic of China.
Bai-Liu
BL
Ya
Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272129, People's Republic of China.
Hong-Fang
HF
Li
Department of Physiology, Jining Medical University, 16 He-hua Street, Bei-hu District, Jining, Shandong, 272067, People's Republic of China.
Hai-Ying
HY
Wang
Department of Physiology, Jining Medical University, 16 He-hua Street, Bei-hu District, Jining, Shandong, 272067, People's Republic of China.
Fei
F
Wu
Department of Physiology, Jining Medical University, 16 He-hua Street, Bei-hu District, Jining, Shandong, 272067, People's Republic of China.
Qing
Q
Xin
Department of Physiology, Jining Medical University, 16 He-hua Street, Bei-hu District, Jining, Shandong, 272067, People's Republic of China.
Hong-Ju
HJ
Cheng
School of Forensic and Laboratory Medicine, Jining Medical University, Jining, Shandong, 272067, People's Republic of China.
Wen-Juan
WJ
Li
Department of Physiology, Jining Medical University, 16 He-hua Street, Bei-hu District, Jining, Shandong, 272067, People's Republic of China.
Na
N
Lin
Department of Physiology, Jining Medical University, 16 He-hua Street, Bei-hu District, Jining, Shandong, 272067, People's Republic of China.
Zai-Hua
ZH
Ba
Jining First People's Hospital, Jining, Shandong, 272011, People's Republic of China.
Ru-Juan
RJ
Zhang
School of Clinical Medicine, Jining Medical University, Jining, Shandong, 272067, People's Republic of China.
Qian
Q
Liu
School of Clinical Medicine, Jining Medical University, Jining, Shandong, 272067, People's Republic of China.
Ya-Nan
YN
Li
Department of Physiology, Jining Medical University, 16 He-hua Street, Bei-hu District, Jining, Shandong, 272067, People's Republic of China.
Bo
B
Bai
Department of Physiology, Jining Medical University, 16 He-hua Street, Bei-hu District, Jining, Shandong, 272067, People's Republic of China. Fenggejnmu@sina.com.
Feng
F
Ge
D000818:Animals; D061745:Antioxidant Response Elements / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*
D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D008315:Malondialdehyde; C008046:5-hydroxymethylfurfural; D005662:Furaldehyde; D051547:Heme Oxygenase-1; D005721:Glutamate-Cysteine Ligase
5-hydroxymethyl-2-furfural; Neuroprotection; Nrf2; Oxidative stress; Transient global cerebral ischemia