| Summary: | 碩士 === 亞洲大學 === 生物科技學系碩士班 === 99 === Arsenic (As) is a human carcinogen and endothelial toxin. Exposures
to arsenic cause various health effects in humans and animals, such as Blackfoot disease and cancers. Selenium (Se) is an essential trace element for growth and reproduction in animals and humans. Selenium affect in arsenic-induced endothelial toxicity through antioxidative protection, and modulation of cell proliferation, and cell cycle progression. Although Se can inhibit the growth of drug-resistant cancer cells, the function of Se on multidrug resistance transporter is still unclear. The objective of this study was to investigate the effect and the possible mechanisms of selenocompounds and selenium-enriched broccoli extract (H-SeB) on
As-induced toxicity in porcine aortic endothelial cells (PECs). The PECs were pretreated with 1 μM of selenite, selenate, selenomethionine, selenomethylselenocysteine or H-SeB for 24 hr, and then treated with 20 or 40 μM arsenic trioxide (As2O3) for investigation of cytotoxicity, cell cycle progression, apoptosis event, antioxidative enzyme activity and the gene expression of multidrug resistance associated-transpoters. The results showed that all selenopounds at 1 μM significantly protected PECs from 20 μM As2O3-induced cytotoxicity, but did not affect apoptosis. The cellular glutathione peroxidase (cGPX) activity, as well as
selenoprotein W (SeW) and glutathione-S-transferase A1 (GSTA1) mRNA expressions were increased by selenocompoumds, therefore, the possible mechanism for selenocompounds to protect PECs from 20 μM
As2O3-induced cytotoxicity may be due to the increase in antioxidative enzyme activity and related gene expression. The results in this study indicated that 1 μM H-SeB pretreated for 24 hr significantly protected PECs from 20 μM As2O3-induced cytotoxicity with reduced secondary necrosis due to apoptosis. In addition, the As-induced cGPX activities as well as gene expressions of SeW, GSTA1, MDR1 and MRP2 were increased by H-SeB pretreated. Thus, the possible mechanism for H-SeB to protect PECs in order to increase live cells, antioxidative ability and As exclusion from 20 μM As2O3-induced cytotoxicity may be through the modulations of apoptosis, antioxidative as well as the related gene expressions of antioxidative enzyme and multidrug resistance associated transporters.
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