Toxicity of thallium on isolated rat liver mitochondria: The role of oxidative stress and MPT pore opening
Article first published online: 30 AUG 2013
© 2013 Wiley Periodicals, Inc.
Volume 30, Issue 2, pages 232–241, February 2015
How to Cite
Eskandari, M. R., Mashayekhi, V., Aslani, M. and Hosseini, M.-J. (2015), Toxicity of thallium on isolated rat liver mitochondria: The role of oxidative stress and MPT pore opening. Environ. Toxicol., 30: 232–241. doi: 10.1002/tox.21900
- Issue published online: 25 JAN 2015
- Article first published online: 30 AUG 2013
- Manuscript Accepted: 29 JUL 2013
- Manuscript Revised: 21 JUL 2013
- Manuscript Received: 5 MAR 2013
- isolated mitochondria;
- oxidative stress;
- cytochrome c;
- mitochondrial permeability transition
Thallium(I) is a highly toxic heavy metal; however, up to now, its mechanisms are poorly understood. The authors' previous studies showed that this compound could induce reactive oxygen species (ROS) formation, reduced glutathione (GSH) oxidation, membrane lipid peroxidation, and mitochondrial membrane potential (MMP) collapse in isolated rat hepatocyte. Because the liver is the 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 toxicity. Mitochondria were isolated from rat liver and incubated with different concentrations of thallium (25–200 µM). Thallium(I)-treated mitochondria showed a marked elevation in oxidative stress parameters accompanied by MMP collapse when compared with the control group. These results showed that different concentrations of thallium (25–200 µM) induced a significant (P < 0.05) increase in mitochondrial ROS formation, ATP depletion, GSH oxidation, mitochondrial outer membrane rupture, mitochondrial swelling, MMP collapse, and cytochrome c release. In general, these data strongly supported that the 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. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 232–241, 2015.