Mechanistic approach of Thallium (I): Involvement of Mitochondrial toxicity

Introduction: Thallium (I) is a highly toxic heavy metal; however, up to now, its mechanisms are poorly understood. Previous studies showed that this compound could induce reactive oxygen species (ROS) formation and membrane lipid peroxidation in isolated rat hepatocyte. Since, the liver is the main storage site of thallium, it seems that the liver mitochondria are one of the important targets for hepatotoxicity. In this investigation, the effects of thallium on mitochondria were studied to investigate its mechanisms of toxicityMaterial and Methods: Mitochondria were isolated from rat liver and incubated with thallium (25–200 mM) for one hour. Then, we planned to determine the role of oxidative stress on isolated rat liver mitochondria by measuring multi-parametric oxidative stress assay.Results: Our data showed that thallium (25–200 mM) induced a significant rise in mitochondrial ROS formation, ATP depletion, glutathione (GSH) oxidation, mitochondrial outer membrane rupture, mitochondrial swelling, MMP collapse, and cytochrome c release (P < 0.05).Discussion: Present data strongly supported that thallium (I)-induced liver toxicity is a result of the disruptive effect of this metal on the mitochondrial respiratory complexes (I, II, and IV), which are the obvious causes of metal-induced ROS formation and ATP depletion. The latter two events, in turn, trigger cell death signaling via opening of mitochondrial permeability transition pore and cytochrome c expulsion.

کلیدواژه ها:

Thallium (I) ، isolated mitochondria ، oxidative stress ، cytochrome c ، mitochondrial permeability transition