title: [Effects of acute exposure to high altitude on hepatic function and CYP1A2 and CYP3A4 activities in rats].
abstract: OBJECTIVE
  To investigate the changes in hepatic functions and activities of CYP1A2 and CYP3A4 in rats after acute exposure to high altitude.
  
  
  METHODS
  Twelve healthy male Wistar rats were randomly divided into control group and exposure group for acute exposure to normal and high altitude (4010 m) environment. Blood samples were collected from the vena orbitalis posterior for detection of the hepatic function. Hepatic pathologies of the rats were examined microscopically with HE staining. Liver microsomes were extracted by differential centrifugation to assess the activities of CYP1A2 and 3A4 using P450-GloTM kit.
  
  
  RESULTS
  In rats with acute exposure to high altitude, AST, ALT, and ALP all increased significantly by 48.50%, 47.90%, and 103.02%, respectively, and TP decreased significantly by 17.80% as compared with those in rats maintained in normal altitude environment (P<0.05). Pathological examination of the liver revealed edema of the central vein of the liver and hepatocyte karyopyknosis in rats after acute exposure to high altitude, which also resulted in significantly lowered activities of CYP1A2 and 3A4 in the liver (by 96.56% and 43.53%, respectively).
  
  
  CONCLUSIONS
  Acute exposure to high altitude can cause obvious liver injuries and lowered activities of CYP1A2 and 3A4 in rats to severely affect drug metabolism in the liver and result in increased concentration, prolonged half-life and reduced clearance of drugs.
authors.affiliation: Key Laboratory of Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou 730050, China.E-mail: yfcs2002@163.com.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Li
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Jia
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.forename: Juanhong
authors.initials: J
authors.lastname: Zhang
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Hao
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
mesh_terms: D000531:Altitude; D000818:Animals; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism*; D008099:Liver / Q000473:pathology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003580:Cytochromes; C017170:Cyp1a2 protein, rat; C465260:Cyp3a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A