Mitochondria as an important target in heavy metal toxicity in rat hepatoma AS-30D cells
- Laboratory of Comparative Biochemistry of Inorganic Ions, Sechenov Institute of Evolutionary Physiology and Biochemistry, Thorez pr. 44, 194223, St.-Petersburg (Russian Federation)
- Nencki Institute of Experimental Biology, Pasteura 3, 02-093 Warsaw (Poland)
The mechanisms of toxic effects of divalent cations of three heavy metals Hg, Cd and Cu in rat ascites hepatoma AS-30D cells cultivated in vitro were compared. It was found that the toxicity of these ions, applied in the micromolar range (10-500 {mu}M), decreased from Hg{sup 2+} (most toxic) to Cu{sup 2+} (least toxic). Hg{sup 2+} and Cd{sup 2+} produced a high percentage of cell death by both necrosis and apoptosis, whereas Cu{sup 2+} at concentrations up to 500 {mu}M was weakly effective. Hg{sup 2+} at concentration of 10 {mu}M appeared slightly uncoupling (i.e., stimulated resting state respiration and decreased the mitochondrial transmembrane potential), whereas it exerted a strong inhibitory effect on the respiratory chain and rapid dissipation of the membrane potential at higher concentrations. Cu{sup 2+} had inhibitory effect on cell respiration only at 500 {mu}M concentration and after incubation of 48 h but produced a significant uncoupling effect at lower concentrations. Cu{sup 2+} induced an early and sharp increase of intracellular production of reactive oxygen species (ROS). The action of Hg{sup 2+} and Cd{sup 2+} on ROS generation was biphasic. They stimulated ROS generation within the cells at low concentrations and at short incubation times but decreased ROS generation at higher concentrations and at longer incubation. It is concluded that mitochondria are an important target for toxic effects of Hg{sup 2+}, Cd{sup 2+} and Cu{sup 2+} in AS-30D rat hepatoma cells.
- OSTI ID:
- 21140924
- Journal Information:
- Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 231; ISSN TXAPA9; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Oxidative stress, mitochondrial permeability transition, and cell death in Cu-exposed trout hepatocytes
The effects of cadmium on coronary blood flow