In vitro modulation of heavy metal-induced rat liver mitochondria dysfunction: A comparison of copper and mercury with cadmium.

Abstract: Cadmium (Cd), mercury (Hg) and copper (Cu) are very toxic environmental pollutants that exert their cytotoxic effects as cations by targeting mitochondria. To further underscore molecular mechanism(s) underlying the heavy metal-induced mitochondrial dysfunction we continued to compare the action of Cd, Hg and Cu using a simple and convenient in vitro model, namely isolated rat liver mitochondria incubated in assay media of different ionic contents and energized by respiratory substrates, glutamate plus malate for complex I, succinate plus rotenone for complex II, and ascorbate plus tetramethylphenylenediamine for complex IV. With the help of various selective electrodes, fluorescent probes, isotope and spectrophotofluorometric techniques, significant differences were found in the modulating action of various substances affecting the activity of these respiratory chain complexes and mitochondrial Ca²⁺ uniporter or permeability transition pore effectors on the mitochondrial function disturbed by the heavy metals, including clear-cut substrate specificity of many effects of these cations. Sequence of events manifested in the mitochondrial dysfunction produced by the metals under test was elucidated. [Copyright &y& Elsevier]