Inhibitory effect of the antioxidant ethoxyquin on electron transport in the mitochondrial respiratory chain

Ethoxyquin (6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline, EQ) is an antioxidant used as a preservative in animal and human foods. In a previous work, we demonstrated that EQ induces an inhibition of renal secretory mechanisms that are dependent on metabolic energy; EQ inhibits renal ATPases. In the present study, we analyzed the effects of EQ on the metabolic pathways of renal and hepatic rat cells, as well as on mitochondria and submitochondrial particles isolated from bovine heart and kidney. EQ induced a mild inhibition of oxygen uptake when it was added to whole homogenates of rat renal cortex in the presence of glucose. In contrast, a strong concentration-dependent inhibition was produced when EQ was added to preparations of intact liver mitochondria or to submitochondrial particles isolated from renal cortex. In the presence of NADH, 90% inhibition was attained at a final concentration of 1 mM EQ. The direct inhibitory effect of EQ on NADH dehydrogenase was a most relevant finding, since no inhibitor for the partial reaction of NADH-ferricyanide on this complex has been reported previously.