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Mitochondria as an important target in heavy metal toxicity in rat hepatoma AS-30D cells
Elena A Belyaeva1, Dorota Dymkowska, Mariusz R Wieckowski
1Laboratory of Comparative Biochemistry of Inorganic Ions, Sechenov Institute of Evolutionary Physiology and Biochemistry, Thorez pr. 44, 194223, St. Petersburg, Russia. alenab61@mail.ru
Abstract:
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 microM), decreased from Hg(2+) (most toxic) to Cu(2+) (least toxic). Hg(2+) and Cd(2+) produced a high percentage of cell death by both necrosis and apoptosis, whereas Cu(2+) at concentrations up to 500 microM was weakly effective. Hg(2+) at concentration of 10 microM 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(2+) had inhibitory effect on cell respiration only at 500 microM concentration and after incubation of 48 h but produced a significant uncoupling effect at lower concentrations. Cu(2+) induced an early and sharp increase of intracellular production of reactive oxygen species (ROS). The action of Hg(2+) and Cd(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(2+), Cd(2+) and Cu(2+) in AS-30D rat hepatoma cells.
Insights
Heavy metals mercury (Hg2+), cadmium (Cd2+), and copper (Cu2+) exhibit varying toxicity in rat hepatoma cells. Mitochondria are a key target, with Hg2+ and Cd2+ inducing cell death and altering reactive oxygen species (ROS) production.
Area of Science:
- Biochemistry
- Cell Biology
- Toxicology
Background:
- Divalent cations of heavy metals like mercury (Hg2+), cadmium (Cd2+), and copper (Cu2+) are known environmental toxins.
- Understanding their specific mechanisms of toxicity in cellular models is crucial for risk assessment.
Purpose of the Study:
- To compare the toxic effects of Hg2+, Cd2+, and Cu2+ on rat ascites hepatoma AS-30D cells in vitro.
- To elucidate the role of mitochondria and reactive oxygen species (ROS) in the toxicity of these heavy metals.
Main Methods:
- Cultured AS-30D rat hepatoma cells were exposed to varying concentrations (10-500 microM) of Hg2+, Cd2+, and Cu2+.
- Cell death (necrosis and apoptosis), mitochondrial transmembrane potential, cellular respiration, and intracellular ROS production were measured.
Main Results:
- Toxicity decreased in the order Hg2+ > Cd2+ > Cu2+.
- Hg2+ and Cd2+ induced significant cell death and had biphasic effects on ROS generation.
- Cu2+ primarily caused mitochondrial uncoupling and increased ROS at higher concentrations and longer incubation times.
Conclusions:
- Mitochondria are a significant target for the toxic actions of Hg2+, Cd2+, and Cu2+ in AS-30D rat hepatoma cells.
- Differential effects on cell death, mitochondrial function, and ROS production characterize the toxicity of these heavy metal ions.
