ABSTRACT
<p><b>OBJECTIVE</b>To observe the protective effect and mechanism of intermittent hypobaric hypoxia (IHH) on cardiomyocytes induced by hydrogen dioxide.</p><p><b>METHODS</b>Male guinea pigs were divided randomly into two groups (n = 10): intermittent hypoxia group (IHH), and control group (non-IHH). The IHH guinea pigs were exposed to a simulated 5,000 m high altitude and hypoxia in hypobaric chamber for 28 d, 6 h/d. The control guinea pigs were kept in the same environment as IHH except hypoxia exposure. Cardiomyocytes were enzymatically isolated from left ventricle of non-CIHH or CIHH guinea pigs. The contractile was assessed in guinea pigs by a video-based motion edge-detection system. The contents and activities of malondialdehyde(MDA), lactate hydrogenase(LDH) and antioxidant enzymes were evaluated by using biochemical methods.</p><p><b>RESULTS</b>1. Hydrogen peroxide could induce contractile and diastole dysfunction, the latent period was longer in IHH cardiac myocytes. 2. After hydrogen peroxide(300 micromol/L, 10 min) perfusion, LDH and MDA contents in supernatant increased significantly in non-IHH and CIHH cardiomyocytes (P < 0.01), Whereas the contents of MDA and LDH in IHH cardiomyocytes were lower than those in non-IHH cardiomyocytes (P < 0.01). 3. The activities of superoxide dismutase (SOD) and catalase (CAT) were significantly increased in the myocardium of IHH guinea pigs, after hydrogen peroxide (300 micromol/L, 10 min) perfusion, SOD and CAT activities decreased significantly in non-IHH and CIHH cardiomyocytes (P < 0.01), whereas the activities of SOD and CAT in CIHH cardiomyocytes were still higher than those in non-IHH cardiomyocytes.</p><p><b>CONCLUSION</b>IHH had a protective effect on cardiomyocytes injury induced by hydrogen peroxide, which might relate with its antioxidation effects.</p>
Subject(s)
Animals , Male , Altitude , Catalase , Metabolism , Cells, Cultured , Guinea Pigs , Hydrogen Peroxide , Pharmacology , Hypoxia , Metabolism , L-Lactate Dehydrogenase , Metabolism , Malondialdehyde , Metabolism , Myocytes, Cardiac , Metabolism , Superoxide Dismutase , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of the cadmium chloride on the DNA damage and the expression of the gadd153 and gadd45beta promoter and mRNA in HepG2 cells.</p><p><b>METHODS</b>DNA damage induced by cadmium chloride was detected by comet assay. The plasmids (pGADD153-Luc and pG45-Luc) containing DNA damage and repair inducible gene 153 and 45 (gadd153 and gadd45beta) promoter and luciferase and gadd45beta reporter gene were constructed. The activity of gadd153 and gadd45beta promoter were represented by the luciferase activity, the inducible luciferase activities was detected by bioluminescence. The expression of gadd153 and gadd45beta mRNA was detected by RT-PCR.</p><p><b>RESULTS</b>The results of comet assay indicated that Olive Tail Moment induced by the cadmium chloride increased significantly at the dose of 100, 300 micromol/L, compared with the control (P < 0.05). The luciferase activity analysis showed that the expression levels of gadd153 promoter increased significantly in 1, 5, 10 micromol/L treatment group, compared with the control (P < 0.05). The expression levels of gadd45beta promoter in 5, 10 micromol/L treatment group were significantly higher than that in control group (P < 0.05). The expression levels of gadd153 mRNA induced by cadmium chloride at the doses of 1, 5, 10 micromol/L and the expression levels of gadd45beta mRNA induced at the doses of 5, 10 micromol/L were significantly higher than thoae in control group (P < 0.05).</p><p><b>CONCLUSION</b>The cadmium chloride can induce the DNA damage and increase the expression levels of the gadd153 and gadd45beta promoters in HepG2 cells.</p>