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Adapted response of the antioxidant defense system to oxidative stress induced by deoxynivalenol in Hek-293 cells

Dinu, Diana, Bodea, Gabriela Oana, Ceapa, Corina Diana, Munteanu, Maria Cristina, Roming, Florentina Israel, Serban, Andreea Iren, Hermenean, Anca, Costache, Marieta, Zarnescu, Otilia, Dinischiotu, Anca
Toxicon 2011 v.57 no.7-8 pp. 1023-1032
antioxidants, caspase-3, catalase, cell death, cell viability, cytotoxicity, deoxynivalenol, feeds, foods, genotoxicity, glutathione peroxidase, glutathione transferase, glutathione-disulfide reductase, humans, inhibitory concentration 50, isocitrate dehydrogenase, kidneys, lipid peroxidation, oxidative stress, reactive oxygen species, superoxide dismutase
The mycotoxin deoxynivalenol (DON), a contaminant of certain foods and feeds, is cytotoxic and genotoxic to mammalians cells. Exposure of human embryonic kidney (Hek-293) cells to DON led to a dose- and time-dependent decrease in cell viability, with an IC₅₀ about 7.6 μM. The DON effects on Hek-293 morphology, reactive oxygen species, lipid peroxidation and antioxidative system and caspase 3 and bcl-2 expression were studied. Cells became round and in some are progressive loss of cell attachment appeared. These biochemical parameters were assessed after 6, 12 and 24 h of treatment with 2.5 and 5 μM DON. An increase in superoxide dismutase activity within the interval 6–12 h and almost complete recovery by the end of experiment for both concentrations was observed, whereas the profile of catalase activity was the same with the superoxide dismutase one for 2.5 μM and decreased in a time-dependent manner for 5 μM. A temporary activation of glutathione peroxidase and glutathione reductase was recorded at 12 h post-exposure, while the glutathione-S-transferase activity was unchanged for both concentrations. The NADP⁺-dependent isocitrate dehydrogenase activity showed a transient increase at the 12 h post-exposure. The caspase 3 expression remained unchanged and the bcl-2 one decreased after 24 h of exposure for the two concentrations. Our results showed the dose- and time specific changes in the antioxidants system of Hek-293 cells, which could not counteract efficiently the effects DON exposure. The different types of cell death which could be activated by this DON induced changes are mentioned.