Identification of targets of the noxious action of 2,2’,5,5’-tetra-chlorbiphenyl in the respiratory chain of rat liver mitochondria

Abstract

The effect of 2,2’,5,5’-tetrachlorinated biphenil (TCB) on the activity of the respiratory chain modules of rat liver mitochondria oxidizing succinate (+ rotenone) in state 3 was studied using a modular kinetic approach. The kinetic dependencies of CoQ and cytochrome c reducing and oxidizing modules on the reduction state of common intermediates (CoQ and citochrome c, respectively) were determined in the control and in the presence of 20 μM TCB. Analysis around cytochrome c revealed that TCB inhibited components of both modules. The same type of analysis around CoQ revealed that TCB had no effect on the kinetics of the CoQ-reducing module, however, it inhibited the CoQ-oxidizing module. In conclusion, our results showed that TCB inhibited cytochrome bc1 but did not affect succinate dehydrogenase. However, this study did not provide evidence whether or not TCB has a direct effect on cytochrome oxidase. Keywords: 2,2’,5,5’- tetrachlorbiphenyl, liver mitochondria, respiratory chain, kinetic analysis