Studies on relative hypoxia in the liver cell caused by environmental chemical agents

1. 在实际环境中评估化学制剂对人体健康的影响时，必须考虑其相互作用。在这项研究中，我们利用灌注大鼠肝脏技术评估了我们日常生活中消耗的化学物质对肝细胞的相对缺氧影响。此外，还研究了不同营养条件对化学制剂相互作用的影响。2. 研究氟芬那酸（FA）对乙醇代谢的影响；(1)摄入乙醇后，经FA预处理的大鼠血液中乙醇和乙醛浓度明显高于对照大鼠；(2)代谢的改变不是由于FA对肝脏线粒体的解偶联作用；(3)而是由于FA对肝脏中乙醛脱氢酶的抑制作用。3. 亚硝酸盐与过氧化氢酶化合物I相互作用，化合物I在灌注的大鼠肝脏中分解为游离态并氧化为硝酸盐，表明在10mM血乙醇浓度时产生最大的抑制作用。4. 研究了乙醇对苯乙烯代谢的影响。在进料条件下，乙醇降低了苯乙烯的代谢速率，而在禁食条件下，乙醇提高了苯乙烯的代谢速率。5. 观察了急性乙醇给药对大鼠运动活动节律的时间依赖性影响。这表明这种时间依赖性是由肝细胞中需氧量（相对缺氧）的生理昼夜节律变化介导的。6. 总之，所有这些结果表明，肝细胞中的相对缺氧通过摄入或暴露于我们日常生活中消耗的实际浓度的化学制剂对生物体产生实质性影响。

1. When assessing the effect of chemical agents on our health in actual environment, interactions of their effects must be considered. In this study, we have assessed effects of relative hypoxia on liver cells caused by chemical agents consumed everyday in our life by using perfused rat liver technique. Furthermore the effect of different nutritional conditions on interactions of chemical agents were also studied. 2. Effect of flufenamic acid (FA) on ethanol metabolism was studied; (1) After ethanol ingestion, blood ethanol and acetaldehyde concentrations were significantly higher in rats pretreated with FA as compared to control rats, (2) the altered metabolism was not due to the uncoupling effect of FA on mitochondria in the liver (3) but rather to a suppressive effect of FA on acetaldehyde dehydrogenase in the liver. 3. Nitrite interacted with catalase compound I followed by the decomposition of compound I to free form and the its oxidation to nitrate in the perfused rat liver, suggesting that the maximal inhibitory action was produced by 10mM blood ethanol concentration. 4. Effect of ethanol on styrene metabolism was studied. Ethanol decreased the rate of styrene metabolism under the fed condition, while ethanol increased the rate of styrene metabolism under the fasted condition. 5. Time-dependent effect of acute ethanol administration on rat locomotor acturity rhythm was observed. It was suggested that this time-dependency was mediated by physiological circadian rhythm change in oxygen demand (relative hypoxia) in the liver cell. 6. In conclusion, all these results suggested that the relative hypoxia in the liver cell produced substantial effects on living organism through ingestion or exposure of actual concentrations of chemical agents consumed in our everyday life.