Interaction of flufenamic acid on ethanol metabolism in rat

Flufenamic acid (FA) is a widely used non-steroidal anti-inflammatory drug. It is also known to be an uncoupling agent of oxidative phosphorylation in mitochondria. The interaction of FA and ethanol has been of concern in the occupational health field, since alcohol consumption is a common habit among members of the working population. Thus, we investigated the effects of FA on ethanol metabolism in the rat. In the first experiment, FA and ethanol were administered intragastrically to male Wistar rats. Ethanol and acetaldehyde were measured in blood samples collected from the tail vein by head-space gas chromatography. In the second experiment, the interaction of FA and ethanol was observed in the perfused rat liver. The following items were monitored in perfused livers from both fed and fastd rats: uptake rate of ethanol, production rate of acetaldehyde, level of reduced pyridine nucleotides, and oxygen consumption rate. In the first experiment, the rats with FA showed significantly higher concentrations of both ethanol and acetaldehyde in blood after ethanol intake than the rats without FA. In the perfused liver, FA suppressed ethanol uptake, and increased acetaldehyde concentration in the effluent. FA decreased the level of intracellular reduced pyridine nucleotides which had been elevated by ethanol. FA caused an increase in the oxygen consumption rate, which was not altered by the coexistence of ethanol. It was concluded that FA suppressed ethanol metabolism due to suppression of acetaldehyde oxidation in the liver, despite its uncoupling effect on oxidative phosphorylation in mitochondria.