Proanthocyanidins Antagonize Arsenic-Induced Oxidative Damage and Promote Arsenic Methylation through Activation of the Nrf2 Signaling Pathway.
Abstract
To investigate the effects of grape seed proanthocyanidin extract (GSPE) on oxidative damage and arsenic (As) methylation and to clarify the role of Nrf2 in the process. L-02 cells were treated with arsenic (25 μM) and GSPE (10, 25, and 50 mg/L) for 24 h. Cell viability was analyzed by MTT assay. Cell apoptosis and ROS fluorescence were detected by flow cytometry. Oxidative stress marker levels were measured using commercial kits. mRNA and protein expression were detected by qRT-PCR and western blotting. The cellular concentrations of methylation products were measured by HPLC-HGAFS. Arsenic methylation ability of cells was determined. Cell survival rate was significantly lower in the As group than in the control group (P < 0.05), while cell apoptosis increased and the number of apoptotic cells decreased gradually after GSPE intervention. Superoxide dismutase, glutathione, and sulfhydryl levels in the intervention group were significantly higher (P < 0.05), while MDA and ROS levels were significantly lower (P < 0.05) than those in the As group. The mRNA and protein expression of Nrf2, HO-1, NQO1, and glutathione-S-transferase increased in the As + GSPE group compared with that in the As group (P < 0.05). GSPE significantly incr...Continue Reading
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