Phenolic Acids Rescue Iron-Induced Damage in Murine Pancreatic Cells and Tissues
Iron is an essential element involved in a variety of physiological functions. However, excess iron catalyzes the generation of reactive oxygen species (ROS) via the Fenton reaction. Oxidative stress, caused by an increase in intracellular ROS production, can be a contributory factor to metabolic sy...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/10/4084 |
| _version_ | 1797598947817029632 |
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| author | Tugba Kose Paul A. Sharp Gladys O. Latunde-Dada |
| author_facet | Tugba Kose Paul A. Sharp Gladys O. Latunde-Dada |
| author_sort | Tugba Kose |
| collection | DOAJ |
| description | Iron is an essential element involved in a variety of physiological functions. However, excess iron catalyzes the generation of reactive oxygen species (ROS) via the Fenton reaction. Oxidative stress, caused by an increase in intracellular ROS production, can be a contributory factor to metabolic syndromes such as dyslipidemia, hypertension, and type 2 diabetes (T2D). Accordingly, interest has grown recently in the role and use of natural antioxidants to prevent iron-induced oxidative damage. This study investigated the protective effect of the phenolic acids; ferulic acid (FA) and its metabolite ferulic acid 4-O-sulfate disodium salt (FAS) against excess iron-related oxidative stress in murine MIN6 cells and the pancreas of BALB/c mice. Rapid iron overload was induced with 50 μmol/L ferric ammonium citrate (FAC) and 20 μmol/L 8-hydroxyquinoline (8HQ) in MIN6 cells, while iron dextran (ID) was used to facilitate iron overload in mice. Cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, ROS levels were determined by dihydrodichlorofluorescein (H2DCF) cell-permeant probe, iron levels were measured by inductively coupled plasma mass spectrometry (ICP-MS), glutathione, SOD (superoxide dismutase) and lipid peroxidation, and mRNA were assayed with commercially available kits. The phenolic acids enhanced cell viability in iron-overloaded MIN6 cells in a dose-dependent manner. Furthermore, MIN6 cells exposed to iron showed elevated levels of ROS, glutathione (GSH) depletion and lipid peroxidation (<i>p</i> < 0.05) compared to cells that were protected by treatment with FA or FAS. The treatment of BALB/c mice with FA or FAS following exposure to ID increased the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) gene levels in the pancreas. Consequently, levels of its downstream antioxidant genes, HO-1, NQO1, GCLC and GPX4, increased in the pancreas. In conclusion, this study shows that FA and FAS protect pancreatic cells and liver tissue from iron-induced damage via the Nrf2 antioxidant activation mechanism. |
| first_indexed | 2024-03-11T03:27:48Z |
| format | Article |
| id | doaj.art-da3d08cd9f7e4bc38230ffed899ed07c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T03:27:48Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-da3d08cd9f7e4bc38230ffed899ed07c2023-11-18T02:39:00ZengMDPI AGMolecules1420-30492023-05-012810408410.3390/molecules28104084Phenolic Acids Rescue Iron-Induced Damage in Murine Pancreatic Cells and TissuesTugba Kose0Paul A. Sharp1Gladys O. Latunde-Dada2Department of Nutritional Sciences, School of Life Course and Population Sciences, King’s College London, Franklin-Wilkins-Building, 150 Stamford Street, London SE1 9NH, UKDepartment of Nutritional Sciences, School of Life Course and Population Sciences, King’s College London, Franklin-Wilkins-Building, 150 Stamford Street, London SE1 9NH, UKDepartment of Nutritional Sciences, School of Life Course and Population Sciences, King’s College London, Franklin-Wilkins-Building, 150 Stamford Street, London SE1 9NH, UKIron is an essential element involved in a variety of physiological functions. However, excess iron catalyzes the generation of reactive oxygen species (ROS) via the Fenton reaction. Oxidative stress, caused by an increase in intracellular ROS production, can be a contributory factor to metabolic syndromes such as dyslipidemia, hypertension, and type 2 diabetes (T2D). Accordingly, interest has grown recently in the role and use of natural antioxidants to prevent iron-induced oxidative damage. This study investigated the protective effect of the phenolic acids; ferulic acid (FA) and its metabolite ferulic acid 4-O-sulfate disodium salt (FAS) against excess iron-related oxidative stress in murine MIN6 cells and the pancreas of BALB/c mice. Rapid iron overload was induced with 50 μmol/L ferric ammonium citrate (FAC) and 20 μmol/L 8-hydroxyquinoline (8HQ) in MIN6 cells, while iron dextran (ID) was used to facilitate iron overload in mice. Cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, ROS levels were determined by dihydrodichlorofluorescein (H2DCF) cell-permeant probe, iron levels were measured by inductively coupled plasma mass spectrometry (ICP-MS), glutathione, SOD (superoxide dismutase) and lipid peroxidation, and mRNA were assayed with commercially available kits. The phenolic acids enhanced cell viability in iron-overloaded MIN6 cells in a dose-dependent manner. Furthermore, MIN6 cells exposed to iron showed elevated levels of ROS, glutathione (GSH) depletion and lipid peroxidation (<i>p</i> < 0.05) compared to cells that were protected by treatment with FA or FAS. The treatment of BALB/c mice with FA or FAS following exposure to ID increased the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) gene levels in the pancreas. Consequently, levels of its downstream antioxidant genes, HO-1, NQO1, GCLC and GPX4, increased in the pancreas. In conclusion, this study shows that FA and FAS protect pancreatic cells and liver tissue from iron-induced damage via the Nrf2 antioxidant activation mechanism.https://www.mdpi.com/1420-3049/28/10/4084iron overloadpancreatic beta cellsROSantioxidant activity |
| spellingShingle | Tugba Kose Paul A. Sharp Gladys O. Latunde-Dada Phenolic Acids Rescue Iron-Induced Damage in Murine Pancreatic Cells and Tissues Molecules iron overload pancreatic beta cells ROS antioxidant activity |
| title | Phenolic Acids Rescue Iron-Induced Damage in Murine Pancreatic Cells and Tissues |
| title_full | Phenolic Acids Rescue Iron-Induced Damage in Murine Pancreatic Cells and Tissues |
| title_fullStr | Phenolic Acids Rescue Iron-Induced Damage in Murine Pancreatic Cells and Tissues |
| title_full_unstemmed | Phenolic Acids Rescue Iron-Induced Damage in Murine Pancreatic Cells and Tissues |
| title_short | Phenolic Acids Rescue Iron-Induced Damage in Murine Pancreatic Cells and Tissues |
| title_sort | phenolic acids rescue iron induced damage in murine pancreatic cells and tissues |
| topic | iron overload pancreatic beta cells ROS antioxidant activity |
| url | https://www.mdpi.com/1420-3049/28/10/4084 |
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