Mode of action of aspirin. Effect of dietary aspirin on mitochondrial pyruvate metabolism in normal and thiamine-deficient rats.

Diets containing 0.2% acetylsalicylic acid were fed to control and thiamine-deficient rats. Acetylsalicylic acid caused a significant decrease in body weight and adipose tissue weight in thiamine-deficient acetylsalicylic acidtreated but not in normal acetylsalicylic acid-treated rats. A large decrease in the total blood ketone bodies in thiaminedeficient acetylsalicylic acid-treated rats was observed. A significant decrease in the blood /3-hydroxybutyrate to acetoacetate ratio in both control and thiamine-deficient rats treated with aspirin was noted. Rat liver mitochondria from both control, thiamine-deficient, and acetylsalicylic acid fed rats were incubated in the presence of ATP, Mg+2, Pi, pyruvate, and radioactive bicarbonate, and synthesis of dicarboxylic acids was examined. It was found that in acetylsalicylic acid-treated rats, the pyruvate utilization and 14C02 incorporation and organic acids formation were greatly decreased. Addition of octanoylcarnitine greatly stimulated 14C02 incorporation into organic acids in thiamine-deficient and acetylsalicylic acid-treated rats. The percentage of pyruvate carboxylated in the presence of octanoylcarnitine was significantly increased in mitochondria from all animals.