The in vitro effects of tannic acid on rat liver mitochondrial respiration and oxidative phosphorylation.

Abstract

The in vitro effects of tannic acid on the membrane structure and function of rat liver mitochondria were investigated. The respiratory control ratio (RCR) decreased by about 50% on addition of 50 μg/ml tannic acid to highly coupled mitochondria, but the adenosine -5'- diphosphate/oxygen (ADP/O) ratio was constant. The uncoupler-induced respiration was also inhibited in the same manner as the RCR. Moreover, the respiratory control disappeared and the ADP/O ratio could not be measured at concentrations of tannic acid above 100 μg/ml. On the other hand, the oxygen consumption rate of succinate-dependent respiration decreased on addition of more than 100 μg/ml tannic acid (50% inhibitory concentration (IC50) = 150 μg/ml tannic acid) to mitochondria. These findings suggest that tannic acid at lower concentrations inhibits the electron transport system to decrease the RCR, but does not impair the membrane, retaining the coupled reaction, while at higher concentrations it impairs the structural integrity of mitochondrial membranes, and directly inhibits the electron transport system.Tannic acid inhibited the succinate oxidase, reduced nicotinamide adenine dinucleotide (NADH) oxidase, succinate dehydrogenase, and NADH dehydrogenase activities of submitochondrial particles (SMP). The IC50 values of tannic acid toward these enzyme systems were estimated to be 35, 45, 30, and 15 μg/ml, respectively. Tannic acid competitively inhibited succinate dehydrogenase and NADH dehydrogenase. However, it did not show significant inhibition of the cytochrome oxidase activity of SMP. It is thus concluded that tannic acid exerts its effect on mitochondrial respiration and oxidative phosphorylation through action on the membrane and on both succinate dehydrogenase and NADH dehydrogenase of mitochondria.