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

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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.