Dataset Information

Proanthocyanidins Antagonize Arsenic-Induced Oxidative Damage and Promote Arsenic Methylation through Activation of the Nrf2 Signaling Pathway.

ABSTRACT:

Purpose

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.

Methods

L-02 cells were treated with arsenic (25??M) 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.

Results

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 increased methylated As level, primary methylation index, secondary methylation index, average growth rate of methylation, and average methylation speed compared with the GSPE untreated group (P < 0.05). After Nrf2 inhibition, the effect of GSPE decreased significantly.

Conclusion

GSPE activates the Nrf2 signaling pathway to antagonize As-induced oxidative damage and to promote As methylation metabolism. Therefore, GSPE may be a potential agent for relieving As-induced hepatotoxicity.

SUBMITTER: Xu M

PROVIDER: S-EPMC6360624 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proanthocyanidins Antagonize Arsenic-Induced Oxidative Damage and Promote Arsenic Methylation through Activation of the Nrf2 Signaling Pathway.

Xu Mengchuan M Niu Qiang Q Hu Yunhua Y Feng Gangling G Wang Haixia H Li Shugang S

Oxidative medicine and cellular longevity 20190120

<h4>Purpose</h4>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.<h4>Methods</h4>L-02 cells were treated with arsenic (25 <i>μ</i>M) 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 ...[more]

PMID: 30805085

Similar Datasets

Project description:Lead is harmful for human health and animals. Proanthocyanidins (PCs), a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect of PCs on the hepatotoxicity of male Kunming mice induced by chronic lead exposure. A total of 70 healthy male Kunming mice were averagely divided into four groups: control group, i.e., the group exposed to lead, the group treated with PCs, and the group co-treated with lead and PCs. The mice exposed to lead were given water containing 0.2% lead acetate. Mice treated in the PCs and PCs lead co-treated groups were given PC (100 mg/kg) in 0.9% saline by oral gavage. Lead exposure caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, and inhibition of antioxidant enzyme activities. The induction of oxidative stress and histological alterations in the liver were minimized by co-treatment with PCs. Meanwhile, the number of Transferase-Mediated Deoxyuridine Triphosphate-Biotin Nick End Labeling (TUNEL)-positive cells was significantly reduced in the PCs/lead co-treated group compared to the lead group. In addition, the lead group showed an increase in the expression level of Bax, while the expression of Bcl-2 was decreased. Furthermore, the lead group showed an increase in the expression level of endoplasmic reticulum (ER) stress-related genes and protein (GRP78 and CHOP). Co-treated with PCs significantly reversed these expressions in the liver. PCs were, therefore, demonstrated to have protective, antioxidant, and anti-ER stress and anti-apoptotic activities in liver damage caused by chronic lead exposure in the Kunming mouse. This may be due to the ability of PCs to enhance the ability of liver tissue to protect against oxidative stress via the Nrf2/ARE signaling pathway, resulting in decreasing ER stress and apoptosis of liver tissue.

Project description:BackgroundInorganic arsenic is an environmental carcinogen that may act through multiple mechanisms including formation of methylated derivatives in vivo. Sodium arsenite (up to 5.0 microM) renders arsenic methylation-competent TRL1215 rat liver epithelial cells tumorigenic in nude mice at 18 weeks of exposure and arsenic methylation-deficient RWPE-1 human prostate epithelial cells tumorigenic at 30 weeks of exposure. We assessed the role of arsenic biomethylation in oxidative DNA damage (ODD) using a recently developed immuno-spin trapping method.MethodsImmuno-spin trapping was used to measure ODD after chronic exposure of cultured TRL1215 vs RWPE-1 cells, or of methylation-competent UROtsa/F35 vs methylation-deficient UROtsa human urothelial cells, to sodium arsenite. Secreted matrix metalloproteinase (MMP)-2 and -9 activity, as analyzed by zymography, cellular invasiveness by using a transwell assay, and colony formation by using soft agar assay were compared in cells exposed to arsenite with and without selenite, an arsenic biomethylation inhibitor, to assess the role of ODD in the transition to an in vitro cancer phenotype.ResultsExposure of methylation-competent TRL1215 cells to up to 1.0 microM sodium arsenite was followed by a substantial increase in ODD at 5-18 weeks (eg, at 16 weeks with 1.0 microM arsenite, 1138% of control, 95% confidence interval [CI] = 797% to 1481%), whereas exposure of methylation-deficient RWPE-1 cells to up to 5.0 microM arsenite did not increase ODD for a 30-week period. Inhibition of arsenic biomethylation with sodium selenite abolished arsenic-induced ODD and invasiveness, colony formation, and MMP-2 and -9 hypersecretion in TRL1215 cells. Arsenic induced ODD in methylation-competent UROtsa/F35 cells (eg, at 16 weeks, with 1.0 microM arsenite 225% of control, 95% CI = 188% to 262%) but not in arsenic methylation-deficient UROtsa cells, and ODD levels corresponded to the levels of increased invasiveness, colony formation, and hypersecretion of active MMP-2 and -9 seen after transformation to an in vitro cancer phenotype.ConclusionArsenic biomethylation appears to be obligatory for arsenic-induced ODD and appears linked in some cells with the accelerated transition to an in vitro cancer phenotype.

Dataset Information

Proanthocyanidins Antagonize Arsenic-Induced Oxidative Damage and Promote Arsenic Methylation through Activation of the Nrf2 Signaling Pathway.

Purpose

Methods

Results

Conclusion

Publications

Proanthocyanidins Antagonize Arsenic-Induced Oxidative Damage and Promote Arsenic Methylation through Activation of the Nrf2 Signaling Pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets