Enhancing effect of lonidamine on the inhibition of mitochondrial respiration by adriamycin.

Pretreatment of rat liver mitochondria with lonidamine (LND), 1-(2,4 dichlorobenzyl)-1 H-indazol-3-carboxylic acid, increases their susceptibility to respiratory inhibition by adriamycin (ADM). Because LND does not inhibit the rate of oxygen consumption at the concentrations used, its potentiating effect may be exerted by favoring the interaction of ADM molecules with their sites in the inner mitochondrial membrane. LND does not modify the permeability on the inner membrane for large molecules. However, its enhancing effect can be ascribed to a modified permeability of the outer mitochondrial membrane which may represent a barrier for ADM entry.