RESUMO
The cytotoxicity of citrinin was evaluated in an established cell line of baby hamster kidney cells. The primary effect of the mycotoxin was on the adherence of the cells to the culture bottles. Microscopic evaluation of morphological alterations indicated that the cells which were originally elongated and flattened, became swollen and round. Electron microscopic examination showed that citrinin (0.1, 0.5 and 1.0 mM) incubated for 10 hours with cultured cells, promoted drastic alterations of normal mitochondria, with swelling and cell death. Transplasma membrane redox system is inhibited by citrinin (81%). This effect is dependent not only on the toxin concentration, but also on the time of exposure to the cells.
Assuntos
Citrinina/farmacologia , Rim/citologia , Animais , Adesão Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/fisiologia , Membrana Celular/ultraestrutura , Células Cultivadas , Cricetinae , Relação Dose-Resposta a Droga , Rim/efeitos dos fármacos , Rim/ultraestrutura , Microscopia Eletrônica , Mitocôndrias/metabolismo , Mitocôndrias/fisiologia , Mitocôndrias/ultraestrutura , Oxirredução , Fatores de TempoRESUMO
Effect of methotrexate (MTX) on mitochondrial oxygen uptake, oxidative phosphorylation and on the activity of several enzymes linked to respiratory chain was studied. MTX was able to inhibit state III respiration activated by ADP and to decrease the respiratory coefficient with the substrates alpha-ketoglutarate and glutamate; these effects became pronounced when mitochondria were pre-incubated with MTX for 10 min. No effect was observed on ATPase activity of undamaged or broken mitochondria; the same was true for NADH-oxidase, NADH-dehydrogenase, NADH-cytochrome c reductase, succinate oxidase, and cytochrome c oxidase activity. The effect on the steady-state of cytochrome b, as well as, the inhibitory effect on state III of respiration with NAD+-linked substrates, offers a reasonable possibility to suggesting that the inhibition site of MTX could be in a place anterior to cytochrome b region, and not linked to respiratory chain.