Rong Wang1, Yuhuan Sun2, Qiang Yin2, Hua Xie3, Wenbin Li3, Chang Wang2, Jiankui Guo3, Ying Hao2, Rui Tao2, Zhengping Jia2. 1. 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. 2. 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. 3. Key Laboratory of the plateau of environmental damage control, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, 730050, China.
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. METHODS AND 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 b5 were 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.
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. METHODS AND 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 b5 were 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: Rong Chang; Jinchun Wu; Xiaofei Zhang; Yi Ye; Wenqin Zhou; Yanmin Liu Journal: Evid Based Complement Alternat Med Date: 2021-10-31 Impact factor: 2.629