Comparative study of the effects of biphenyl and Kanechlor-400 on the respiratory and energy linked activities of rat liver mitochondria.

A comparative study of the effects of biphenyl and Kanechlor-400 (KC-400) on the respiratory and energy linked activities of rat liver mitochondria was made, and some differences in effects caused by the chlorination of biphenyl were clarified. The inhibition of state 3 respiration with succinate by biphenyl was less than that observed with alpha-ketoglutarate/malate. By contrast, KC-400 exhibited the opposite trend; state 3 respiration with succinate was more sensitive to inhibition than that observed with alpha-ketoglutarate/malate. Thus the inhibition of state 3 respiration with NAD+-linked substrate was decreased, whereas the inhibition of state 3 respiration with succinate was increased by the chlorination of aromatic rings. Biphenyl also instantaneously stimulated state 4 respiration. The extent of stimulation with succinate by biphenyl was larger than with alpha-ketoglutarate-malate. On the other hand, there was about a 1-2 minute lag period before stimulation of state 4 respiration by KC-400 became obvious. Furthermore, state 4 respiration in the presence of alpha-ketoglutarate/malate was more intensely stimulated by KC-400 than by succinate. Biphenyl and KC-400 dissipated the membrane potential across the mitochondrial membranes. The dissipation of membrane potential by biphenyl was instantaneous whereas that caused by KC-400 was preceded by a lag period (1-2 min). Biphenyl and KC-400 altered the permeability properties of mitochondrial membranes as evidenced by the release of endogenous K+. The release of K+ due to biphenyl was instantaneous but KC-400 induced K+-release was preceded by a lag period (1-2 min). Thus membrane perturbation by biphenyl was faster than that induced by KC-400. Therefore, it is clear that the chlorination of aromatic rings delays the perturbation in the state of membrane lipids.