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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 4300 m. 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 (55 m), Group B (4300 m) and Group C (metronidazole intervention, 4300 m). 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 b 5 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. [ABSTRACT FROM AUTHOR]

Large tumor suppressor 2 (LATS2), an important mediator of the cell apoptotic response pathway, has been linked to the progression of several cancers. Here, we described the molecular feature of LATS2 as a novel antitumor factor in liver cancer cells in vitro. Western blotting was used to detect the expression of LATS2 and its downstream factors. ELISA, immunofluorescence, and flow cytometry were used to evaluate the alterations of mitochondrial function in response to LATS2 overexpression. Adenovirus-loaded LATS2 and siRNA against DRP1 were transfected into liver cancer cells to overexpress LATS2 and knockdown DRP1 expression, respectively. The results of the present study demonstrated that overexpression of LATS2 was closely associated with more liver cancer cell death. Mechanistically, LATS2 overexpression increased the expression of DRP1, and DRP1 elevated mitochondrial division, an effect that was accompanied by mitochondrial dysfunction, including mitochondrial membrane potential reduction, mitochondrial respiratory complex downregulation, mitochondrial cyt-c release into the nucleus and mitochondrial oxidative injury. Moreover, LATS2 overexpression also initiated mitochondrial apoptosis, and this process was highly dependent on DRP1-related mitochondrial division. Molecular investigations demonstrated that LATS2 modulated DRP1 expression via the Wnt/β-catenin pathway. Inhibition of the Wnt/β-catenin pathway pregented LATS2-mediated DRP1 upregulation, ultimately sustaining mitochondrial function and cell viability in the presence of LATS2 overexpression. Altogether, the above data identify LATS2-Wnt/β-catenin/DRP1/mitochondrial division as a novel anticancer signaling pathway promoting cancer cell death, which might be an attractive therapeutic target for the treatment of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]