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). Conclusion 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.