title: The activity, protein, and mRNA expression of CYP2E1 and CYP3A1 in rats after exposure to acute and chronic high altitude hypoxia.
abstract: The effects of exposure to acute and chronic high altitude hypoxia on the activity and expression of CYP2E1 and CYP3A1 were examined in rats. Rats were divided into low altitude (LA, 400 m), acute moderate altitude hypoxia (AMH, 2800 m), chronic moderate altitude hypoxia (CMH, 2800 m), acute high altitude hypoxia (AHH, 4300 m), and chronic high altitude hypoxia groups (CHH, 4300 m). Probe drugs were administrated orally to all five groups. Then the serum concentration of probe drug and its metabolite was determined by RP-HPLC. The activity of CYP2E1 and CYP3A1 was evaluated using the ratio of the metabolite to chlorzoxazone and testosterone, respectively. ELISA and real-time PCR were used to analyze the protein and mRNA expression of CYP2E1 and CYP3A1 in liver microsomes, respectively. Chronic high altitude hypoxia caused significant decreases in the activity and protein and mRNA expression of rat CYP2E1 and CYP3A1 in vivo. Acute high altitude hypoxia was not found to change the activity, protein or mRNA expression of rat CYP2E1 or CYP3A1. This study showed significant changes in the activity and protein and mRNA expression of CYP2E1 or CYP3A1 in rats after exposure to chronic high altitude hypoxia.
authors.affiliation: 1 Department of Pharmacy, Qinghai University Medical College , Xining, China .
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Li
authors.forename: Xuejun
authors.initials: X
authors.lastname: Wang
authors.forename: Yongping
authors.initials: Y
authors.lastname: Li
authors.forename: Junbo
authors.initials: J
authors.lastname: Zhu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Su
authors.forename: Xingchen
authors.initials: X
authors.lastname: Yao
authors.forename: Xueru
authors.initials: X
authors.lastname: Fan
authors.forename: Yabin
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000208:Acute Disease; D000531:Altitude; D000532:Altitude Sickness / Q000201:enzymology*; D000818:Animals; D002753:Chlorzoxazone / Q000097:blood; D002908:Chronic Disease; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood
chemical_list: D012333:RNA, Messenger; D013739:Testosterone; D019392:Cytochrome P-450 CYP2E1; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A; D002753:Chlorzoxazone
keywords: CYP2E1; CYP3A1; activity; expression; high altitude; hypoxia