RESUMO
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.
Assuntos
Respiração Celular/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Nitrato de Uranil/farmacologia , 2,4-Dinitrofenol/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Guanina/análogos & derivados , Guanina/metabolismo , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/metabolismo , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Mitocôndrias Hepáticas/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
It is found that in bidistilled water saturated with oxygen hydrogen peroxide and hydroxyl radicals are formed under the influence of visible and infrared radiation in the absorption bands of molecular oxygen. Formation of reactive oxygen species (ROS) occurs under the influence of both solar and artificial light sourses, including the coherent laser irradiation. The oxygen effect, i.e. the impact of dissolved oxygen concentration on production of hydrogen peroxide induced by light, is detected. It is shown that the visible and infrared radiation in the absorption bands of molecular oxygen leads to the formation of 8-oxoguanine in DNA in vitro. Physicochemical mechanisms of ROS formation in water when exposed to visible and infrared light are studied, and the involvement of singlet oxygen and superoxide anion radicals in this process is shown.
Assuntos
DNA/química , Guanina/análogos & derivados , Radical Hidroxila/química , Oxigênio/química , Superóxidos/química , Água/química , Dano ao DNA , Guanina/química , Peróxido de Hidrogênio/química , Raios Infravermelhos , Cinética , Lasers , Oxigênio Singlete/química , Energia Solar , Soluções/química , Raios UltravioletaRESUMO
The formation of long-lived radicals in the solutions of casein and its hydrolysate with an equimolar mixture of amino acids was compared by measuring the X-ray-induced chemiluminescence. It was shown that free amino acids constituting the protein produce long-lived radicals. It was demonstrated that some amino acids (Leu, Ile, Val, Ser, Trp, Met, Pro, Arg, Gly, Phe) emit light of visible spectrum over a long period of time after the irradiation, which indicates the generation of long-lived radicals of these amino acids. The half-life times of these radicals are several hours. Dissolving irradiated dry amino acids capable of luminescing over a long time gives rise to the formation of hydrogen peroxide in aqueous medium.
Assuntos
Aminoácidos/efeitos da radiação , Peróxido de Hidrogênio/química , Água/química , Aminoácidos/química , Caseínas/química , Caseínas/efeitos da radiação , Radicais Livres/química , Hidrólise , Medições Luminescentes , Conformação ProteicaRESUMO
It is demonstrated that hydroxyl radicals and hydrogen peroxide are formed under the action of uranyl ions in aqueous solutions containing no reducing agents. In the presence of uranyl ions, formation of 8-oxoguanine in DNA and long-lived protein radicals are observed in vitro. It is shown that the pro-oxidant properties of uranyl at micromolar concentrations mostly result from the physico-chemical nature of the compound rather than its radioactive decay. Uranyl ions lead to damage in DNA and proteins causing death of HEp-2 cells by necrotic pathway. It is revealed that the uranyl ions enhance radiation-induced oxidative stress and significantly increase a death rate of mice exposed to sublethal doses of X-rays.