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

1.在评估实际环境中化学制剂对人体健康的影响时，必须考虑它们之间的相互作用。在本研究中，我们利用大鼠肝脏灌流技术评估了日常生活中化学物质消耗对肝细胞相对低氧的影响。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.研究了氟苯那酸(FA)对乙醇代谢的影响：(1)摄入乙醇后，FA组大鼠血液中乙醇和乙醛浓度显著高于对照组；(2)这种代谢改变不是由于FA对肝脏线粒体的解偶联作用(3)，而是由于FA对肝脏乙醛脱氢酶的抑制作用。3.在灌流的大鼠肝脏中，亚硝酸盐与过氧化氢酶化合物I相互作用，随后化合物I分解为游离态并氧化为硝酸盐，提示10 mM血液乙醇浓度时抑制作用最强。4.研究了乙醇对苯乙烯代谢的影响。乙醇降低了进食条件下的苯乙烯代谢率，而乙醇提高了禁食条件下的苯乙烯代谢率。5.观察急性乙醇给药对大鼠运动节律的时间依赖性影响。有人认为这种时间依赖性是由肝细胞中氧需求(相对低氧)的生理昼夜节律变化所调节的。6.综上所述，所有这些结果都表明，肝细胞中的相对低氧通过摄入或暴露于日常生活中消耗的实际浓度的化学试剂而对生物产生实质性影响。

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.