title: The effects of metronidazole on Cytochrome P450 Activity and Expression in rats after acute exposure to high altitude of 4300m.
abstract: BACKGROUND
  The purpose is to observe the changes of CYP450 enzyme activity expression as well as the physiological and pathological states of Wistar rats given metronidazole drug intervention after acute exposure to high altitude of 4300m.
  
  
  RESULTS
  Thirty healthy adult male Wistar rats of average weight 200 ± 20 g were randomly assigned into three groups of 10 rats per group as follows: Group A (55m), Group B (4300m) and Group C (metronidazole intervention, 4300m). After three days, the main blood gas levels were detected and the liver tissue pathological slices were observed. The enzymatic activity of CYP1A2 and 3A1 as well as the total protein, total CYP450, cytochrome b5 and the protein expression of CYP450 isoforms CYP1A2 and 3A1 were detected. Compared with Group A and Group B, the expression of total CYP450 and CYP1A2 was significantly reduced (P<0.01or P<0.05), the enzymatic activity of CYP1A2 and CYP3A1 were significantly reduced (P<0.05, P<0.01), respectively and CYP3A1 had no significant changes (P>0.05). Compared with Group B and Group C the enzymatic activity of CYP1A2 had no significant changes (P>0.050), the enzymatic activity of CYP3A1 was significantly reduced (P<0.01). The total cytochrome p450, CYP1A2 and cytochrome b5were significantly reduced (P<0.01 and P<0.05), respectively and CYP3A1 had no significant changes (P>0.05). Pathological observation showed that rats in Group A were normal with no significant pathological changes in their livers; rats in Group B suffered from liver injuries and edema with a few of them caught inflammatory cell infiltration; rats in Group C caught liver cell edema, inflammatory diseases and lobular vena cava expansion.
  
  
  CONCLUSIONS
  Acute exposure to high altitude CYP450 isoform expression and the enzymatic activity were significantly reduced, both the physiology and pathology of rats were substantially impaired, and which maybe resulted from the hypoxia and drug intervention interrelated effected in plateau filed test.
authors.affiliation: Key Laboratory of the plateau of environmental damage control, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, 730050, China; College of pharmacy, University of Lanzhou, Lanzhou, 730000, China. Electronic address: wangrong-69@163.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Key Laboratory of the plateau of environmental damage control, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, 730050, China; College of pharmacy, University of Lanzhou, Lanzhou, 730000, China.
authors.forename: Yuhuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory of the plateau of environmental damage control, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, 730050, China; College of pharmacy, University of Lanzhou, Lanzhou, 730000, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Key Laboratory of the plateau of environmental damage control, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, 730050, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.affiliation: Key Laboratory of the plateau of environmental damage control, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, 730050, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of the plateau of environmental damage control, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, 730050, China; College of pharmacy, University of Lanzhou, Lanzhou, 730000, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of the plateau of environmental damage control, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, 730050, China.
authors.forename: Jiankui
authors.initials: J
authors.lastname: Guo
authors.affiliation: Key Laboratory of the plateau of environmental damage control, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, 730050, China; College of pharmacy, University of Lanzhou, Lanzhou, 730000, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Key Laboratory of the plateau of environmental damage control, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, 730050, China; College of pharmacy, University of Lanzhou, Lanzhou, 730000, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Tao
authors.affiliation: Key Laboratory of the plateau of environmental damage control, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, 730050, China; College of pharmacy, University of Lanzhou, Lanzhou, 730000, China.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Jia
mesh_terms: D000064:Acclimatization; D000531:Altitude; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000633:toxicity; D001784:Blood Gas Analysis; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D015786:Cytochromes b5 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D004347:Drug Interactions; D000860:Hypoxia / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008795:Metronidazole / Q000494:pharmacology* / Q000633:toxicity; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D018836:Inflammation Mediators; D008795:Metronidazole; D015786:Cytochromes b5; C017170:Cyp1a2 protein, rat; C465138:Cyp3a23-3a1 protein, rat; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A
keywords: Activity and expression; Acute exposure; Cytochrome P450; High altitude; Metronidazole