title: Effects of N-butylphthalide on the activation of Keap1/Nrf-2 signal pathway in rats after carbon monoxide poisoning.
abstract: Carbon monoxide (CO) is the leading cause of death by poisoning all over the world and may result in neuropathologic changes and cognitive and neurologic sequelae, yet little is known regarding its outcomes. The present study aimed to evaluate the neuroprotective effects of N-butylphthalide (NBP) against brain damage after acute CO poisoning. The animal model of CO poisoning was established by exposed to 1000 ppm CO in air for 40 min and then to 3000 ppm for another 20 min. RT-PCR was used to assess the expressions of apoptosis-associated genes Bcl-2 mRNA and Bax mRNA. Mitochondrial membrane potential (MMP) was detected by fluorescent probe JC-1. Immunohistochemistry stain and Western blot assay were used to evaluate the expression levels of Kelch-like ECH-associated protein 1 (Keapl), nuclear factor erythroid 2-related factor 2 (Nrf-2) and
  quinone oxidoreductase 1(NQO-1). CO poisoning could increase the levels of Bcl-2 mRNA and Bax mRNA expressions, and obviously decrease the MMP of cells. NBP treatment could maintain the high MMP, significantly up-regulate Bcl-2 mRNA and down-regulate Bax mRNA expression, and the ratio of Bcl-2 mRNA/Bax mRNA expressions was higher than that in the CO poisoning group (P<0.05). CO poisoning could start oxidative stress response. The expressions of Keap1, Nrf-2 and NQO-1 proteins significantly increased at 1, 3 and 7 day after NBP administration as compared with the CO poisoning group (P<0.01). These findings suggest that N-butylphthalide may protect mitochondrial function, balance the expressions of anti-apoptosis genes and pro-apoptosis genes, be in part associated with activation of Keap1-Nrf-2/antioxidant response element (ARE) signaling pathway, and play a neuroprotective role in brain damage after acute CO poisoning.
authors.affiliation: Emergency Centre, Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University Medical College, Yantai Yudong 20 Road, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Emergency Centre, Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University Medical College, Yantai Yudong 20 Road, PR China. Electronic address: chengym1967@163.com.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Emergency Centre, Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University Medical College, Yantai Yudong 20 Road, PR China. Electronic address: bimingjun00@163.com.
authors.forename: MingJun
authors.initials: M
authors.lastname: Bi
authors.affiliation: Emergency Centre, Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University Medical College, Yantai Yudong 20 Road, PR China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Lin
authors.affiliation: Emergency Centre, Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University Medical College, Yantai Yudong 20 Road, PR China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Clinical Medicine, Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University Medical College, Yantai Yudong 20 Road, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Emergency Centre, Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University Medical College, Yantai Yudong 20 Road, PR China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Emergency Centre, Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University Medical College, Yantai Yudong 20 Road, PR China.
authors.forename: Hai
authors.initials: H
authors.lastname: Kang
authors.affiliation: Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University Medical College, Qingdao Jiangsu 16 Road, PR China.
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000818:Animals; D017209:Apoptosis; D001572:Benzofurans / Q000633:toxicity*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002249:Carbon Monoxide Poisoning / Q000378:metabolism* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1; D053078:Membrane Potential, Mitochondrial; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001572:Benzofurans; D047908:Intracellular Signaling Peptides and Proteins; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; C027125:3-n-butylphthalide
keywords: Apoptosis-associated gene; CO poisoning; Keapl; MMP; N-Butylphthalide; NQO-1; Nrf-2