Abstract
This study evaluated the kinetic signature of toxicity of four heavy metals known to cause severe health and environmental issues—cadmium (Cd), mercury (Hg) lead (Pb) arsenic (As)—and the mixture of all four metals (Mix) on MCF7 cancer cells, in the presence and absence of the antioxidant glutathione (GSH). The study was carried out using real time cell electronic sensing (RT-CES). RT-CES monitors in real time the electrical impedance changes at the electrode/culture medium interface due to the number of adhered cells, which is used as an index of cell viability. Cells were seeded for 24 h before exposure to the metals and their mixtures. The results showed that in the presence and absence of cellular glutathione, arsenic was the most cytotoxic of all five treatments, inducing cell death after 5 h of exposure. Lead was the least cytotoxic in both scenarios. In the presence of cellular GSH, the cytotoxic trend was As > Cd > MIX > Hg > Pb, while in the absence of GSH, the cytotoxic trend was As > Hg > MIX > Cd > Pb. The findings from this study indicate the significance of glutathione-mediated toxicity of the metals examined—particularly for mercury—and may be clinically relevant for disorders such as autism spectrum disorder where decreased glutathione-based detoxification capacity is associated with increased mercury intoxication.
Highlights
Among heavy metals, cadmium (Cd), mercury (Hg), lead (Pb) and arsenic (As) are some of the most toxic elements due to their persistence in the environment
To characterize the kinetic signature of each of the four chemicals (Cd, Hg, Pb and As) and the mixture of all four (Mix), MCF7 cells were exposed to different concentrations of each chemical and dynamically monitored over 96 h using real time cell electronic sensing (RT-CES)
Exposure of cells to heavy metals may immediately lead to necrosis or apoptosis, but sometimes, cells may undergo series of events like the synthesis of more glutathione molecules that could lead to their survival
Summary
Cadmium (Cd), mercury (Hg), lead (Pb) and arsenic (As) are some of the most toxic elements due to their persistence in the environment. They cause oxidative and nitrosative stress [1,2,3] and damage macromolecules in cells which lead to cell death by apoptosis or necrosis [4]. Metal mixtures substantially complicate the risk assessment process for these elements and very few researchers have studied the environmental effects of mixtures of heavy metals. It is imperative to study heavy metals individually, and in mixtures Information on potential adverse health effects associated with intake of mixture of most frequently found metals contaminant is not known.
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