Spectroscopic and Microscopic Studies on the Mechanisms of Mitochondrial Toxicity Induced by Different Concentrations of Cadmium

The deleterious action of cd(2+) on rat liver mitochondria was investigated in this work using spectroscopic and microscopic methods. The concentration dependence of cd(2+) on mitochondrial swelling, membrane potential and membrane fluidity was studied. Our aim was to detect the active sites of cd(2+) in the mitochondrial membrane treatments with cyclosporin A (CsA) and EGTA on the mitochondrial permeability transition (MPT) induced by low and high concentrations of cd(2+). The protective effects of dithiothreitol, human serum albumin and monobromobimane + on cd(2+)- induced MPT were also monitored. All of these investigations indicated that cd(2+) can directly affect MPT at two separate localization sites at different concentrations: the classic Ca2+ triggering site and the thiol (-SH) groups of membrane proteins matched by MPT pore opening (defined as S site). At the high concentration of cd(2+), other free -SH groups in the mitochondrial matrix may be involved in this process. These findings were supported by transmission electron microscopy and shed light on the toxic mechanism of cd(2+) on mitochondria.