Development of an Experimental System by Using Perfused Organs to Study the Combined Effects of Environmental Factors

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1. When we assess the effect of chemical agents on our health in actual environment, we must consider interractions of their effects. In addition to the interactions between chemical agents, the interactions of chemical agents with some environmental factors including stress and nutrition are also taken into the consideration. We have developed a system consisting of scanning reflectance spectrophotometry and surface fluorometry at the organ level for this purpose. This experimental system enables us to observe the real-time intracellular biochemical changes in perfused rat organs like liver and kidney. 2. Contribution of substrates on eneygy production in perfused rat kidney was studied. L-lactate and alpha-ketoglutarate were efficient substrates for rat kidney to maintain energy metabolism. 3. In the study of effect of stress on trichloroethylene metabolism, it was obtained that 10nM epinephrine increased trichloroethlene metabolism rate in rat liver. 4. Effect of ethanol on styrene metabolism was assessed in the perfused rat liver. Ethanol decreased the rate of styrene uptake in rat liver. And it was suggested that the rate was modified due to changes in nutritional condition.5. Interactions of flufenamic acid (FA), an anti-inflammatory drug, and ethanol on their metabolisms were studied in the perfused liver from rats under fed and fasted conditions. FA suppressed ethanol oxidation at the concentrations of 0.1mM (2mM of ethanol) that could occur in the actual situation. It was also observed that the effect of FA on the ethanol oxidation was modified by the nutritional condition. An uncoupling effect of FA on renal intracellular energy metabolism was studied in the perfused rat kidney. FA decreased the reduced PN level, the fractional reabsorption of Na, and the fractional reabsorption of Ca. It was suggested that function of energy dependent ion transport systems was influenced because of uncoupling effect of FA surpressing ATP production.