Toxic effects of indocyanine green on rat liver mitochondria

Indocyanine green (ICG) (68 to 171 nmol/mg of protein) inhibited the oxygen consumption of rat liver mitochondria in vitro. In state IV respiration, an acceleration of oxygen consumption occurred prior to this inhibition. ICG induced mitochondrial swelling in an isotonic KCl and K ⁺ acetate medium but not in a 0.27 m sucrose medium. The increase in the ⁴²K diffusion space of isolated mitochondria was significantly larger than that of the [ ¹⁴C]sucrose diffusion space, indicating that ICG renders the mitochondrial membrane permeable to K ⁺ ions. At the same time, an efflux of H ⁺ ions from mitochondria was observed. It is concluded that the inhibition of mitochondrial oxygen consumption could be the result of a decrease in substrate penetration, as suggested by the diminution in NAD reduction by glutamate or isocitrate in the presence of ICG, without change in the activity of the corresponding dehydrogenases. A nigericin-like-mediated K ⁺ for H ⁺ antiport is proposed to account for the effects of ICG upon mitochondrial membrane permeability.