title: Impacts of Blast-Induced Traumatic Brain Injury on Expressions of Hepatic Cytochrome P450 1A2, 2B1, 2D1, and 3A2 in Rats.
abstract: The hepatic cytochrome P450 (CYP450) enzyme superfamily is one of the most important drug-metabolizing enzyme systems, which is responsible for the metabolism of a large number of clinically relevant medications used in traumatic brain injury (TBI) therapy. Modification of CYP450 expression may have important influences on drug metabolism and lead to untoward effects on those with narrow therapeutic windows. However, the impact of blast-induced TBI (bTBI) on the expression of CYP450 has received little attention. The subfamilies of CYP1A, 2B, 2D, and 3A account for about 85 % of all human drug metabolism of clinical significance. Therefore, in this study, we investigated the expressions of hepatic CYP1A2, CYP2B1, CYP2D1, and CYP3A2 in rats suffering bTBI. Meanwhile, we also measured some important cytokines in serum after injury, and calculated the correlation between these cytokines and the expressions of CYP1A2, CYP2B1, CYP2D1, and CYP3A2. The results showed that bTBI could significantly reduce mRNA expressions of CYP1A2, CYP2D1, and CYP3A2 at the early stage and induce the expressions from 48 h to 1 week after injury. The protein expressions of these CYP450s had all been downregulated from 24 to 48 h post- injury, and then began to elevate at 48 h after bTBI. The cytokines, IL-1β, IL-2, IL-6, and TNF-α, increased significantly in the early phase, and began to reduce at the delayed phase of bTBI. The serum levels of IL-1β, IL-6, and TNF-α but not IL-2 were significantly negative correlated with the mRNA expressions of CYP2B1 and CYP2D1 and the proteins expressions of CYP1A2, CYP2B1, CYP2D1, and CYP3A2. In conclusion, our work has, for the first time, indicated that bTBI has significant impact on the expressions of CYP1A2, CYP2B1, CYP2D1, and CYP3A2, which may be related to the cytokines induced by the injury.
authors.affiliation: Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, Chengdu Second People's Hospital, Chengdu, Sichuan, People's Republic of China.
authors.forename: Junrui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, People's Republic of China.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, People's Republic of China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, People's Republic of China.
authors.forename: Kaihua
authors.initials: K
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, People's Republic of China. gujianwen5000@sina.com.|Department of Neurosurgery, The 306th Hospital of PLA, NO.9, Anxiang Beili, Deshengmen, Chaoyang District, Beijing, 100101, People's Republic of China. gujianwen5000@sina.com.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, People's Republic of China. botao_yu@sina.com.
authors.forename: Botao
authors.initials: B
authors.lastname: Yu
authors.affiliation: College of Materials Science and Engineering, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Yin
authors.affiliation: Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, People's Republic of China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, People's Republic of China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Jin
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000201:enzymology* / Q000473:pathology; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis* / Q000235:genetics; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis* / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis* / Q000235:genetics; D000072467:Cytochrome P450 Family 2 / Q000096:biosynthesis* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C017170:Cyp1a2 protein, rat; C504568:Cyp2d1 protein, rat; C465260:Cyp3a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D019362:Cytochrome P-450 CYP2B1; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2
keywords: Blast traumatic brain injury; Cytochrome 450; Cytokine; Inflammation