Abstract
The mechanisms of cytotoxic effect of uranyl nitrate were studied. It was shown that uranyl nitrate induced HEp-2 cell death, mainly by necrotic way. In the experiments in vitro, uranyl nitrate caused an appearance of 8-oxoguanine in DNA, indicating the induction of oxidative stress. The experiments with isolated rat liver mitochondria revealed that 1 mM uranyl nitrate decreased the respiration rates of mitochondria in state 3 and DNP-induced respiration. At the same time, uranyl nitrate had no influence on the opening of the mitochondrial permeability transition pore and decreased the rate of formation of H2O2 by mitochondria. Possible molecular mechanisms of uranyl-induced necrosis are discussed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2,4-Dinitrophenol / pharmacology
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Animals
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Cell Death / drug effects
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Cell Line, Tumor
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Cell Respiration / drug effects*
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Dose-Response Relationship, Drug
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Guanine / analogs & derivatives
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Guanine / metabolism
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Humans
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Hydrogen Peroxide / antagonists & inhibitors
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Hydrogen Peroxide / metabolism
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Liver / cytology
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Liver / drug effects
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Liver / metabolism
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Male
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Mitochondria, Liver / drug effects*
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Mitochondria, Liver / metabolism
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Mitochondrial Membrane Transport Proteins / metabolism
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Mitochondrial Permeability Transition Pore
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Oxidative Stress / drug effects
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Rats
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Reactive Oxygen Species / metabolism
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Uranyl Nitrate / pharmacology*
Substances
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Mitochondrial Membrane Transport Proteins
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Mitochondrial Permeability Transition Pore
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Reactive Oxygen Species
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Uranyl Nitrate
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8-hydroxyguanine
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Guanine
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Hydrogen Peroxide
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2,4-Dinitrophenol