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1. Yao Xue Xue Bao. 2012 Feb;47(2):188-93.

[Effect of high altitude hypoxia on the activity and protein expression of CYP2C9
and CYP2C19].

[Article in Chinese]

Li XY, Liu YN, Yuan M, Li YP, Yang YZ, Zhu JB.

Department of Pharmacy, Medical College of Qinghai University, Xining 810001,
China. qhmclxy@163.com

This study is to investigate the effect of high altitude hypoxia on the activity
and protein expression of CYP2C9 and CYP2C19. Rats from plain (P) and rats with
acute middle altitude hypoxia (AMH), chronic middle altitude hypoxia (CMH), acute
high altitude hypoxia (AHH) and chronic high altitude hypoxia (CHH) were
administered orally phenytoin sodium (PHT) and omeprazole (OMZ) to evaluate the
activity of CYP2C9 and CYP2C19, separately. The serum concentrations of PHT and
metabolite 4'-hydroxyphenytoin (HPPH) at 12 h after treatment and the serum
concentrations of OMZ and metabolite 5-hydroxy omeprazole (5-OHOMZ) at 3 h after
treatment were determined by RP-HPLC. The activity of CYP2C9 and CYP2C19 was
evaluated by the ratio of HPPH to PHT and the ratio of 5-OHOMZ to OMZ,
respectively. The protein expressions of CYP2C9 and CYP2C19 were determined by
ELISA method. The activities of CYP2C9 (HPPH/PHT) in P, AMH, CMH, AHH and CHH
were 0.67 +/- 0.31, 0.75 +/- 0.29, 0.76 +/- 0.23, 0.79 +/- 0.31 and 0.75 +/-
0.18, respectively, and the activities of CYP2C19 (5-OHOMZ/OMZ) in P, AMH, CMH,
AHH and CHH were 0.17 +/- 0.06, 0.20 +/- 0.10, 0.11 +/- 0.05, 0.37 +/- 0.13 and
0.19 +/- 0.05, respectively. The protein expressions of CYP2C9 in P, AMH, CMH,
AHH and CHH were 4.20 +/- 1.27, 3.95 +/- 0.81, 3.93 +/- 1.11, 4.32 +/- 1.03 and
4.12 +/- 0.86 ng x g(-1), respectively, and the protein expressions of CYP2C19 in
P, AMH, CMH, AHH and CHH were 3.91 +/- 1.82, 3.63 +/- 2.07, 2.55 +/- 0.85, 4.78
+/- 2.37 and 3.51 +/- 1.03 ng x g(-1), respectively. The activities and protein
expressions of CYP2C9 in AMH, CMH, AHH and CHH were not significantly different
with those of P. The protein expressions of CYP2C19 in AMH, CMH, AHH and CHH were
not significantly different with those of P, but the activity of CYP2C19 in AHH
was significantly higher than that of P. This study found significant changes in
the activity of CYP2C19 under the special environment of acute high altitude
hypoxia.

PMID: 22512029 [PubMed - in process]