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Phenolic Acids Rescue Iron-Induced Damage in Murine Pancreatic Cells and Tissues
Tugba Kose1, Paul A Sharp1, Gladys O Latunde-Dada1
1Department of Nutritional Sciences, School of Life Course and Population Sciences, King's College London, Franklin-Wilkins-Building, 150 Stamford Street, London SE1 9NH, UK.
Ferulic acid (FA) and its metabolite (FAS) protect against iron-induced oxidative stress by enhancing cell viability and activating antioxidant pathways. These natural compounds offer a promising strategy for preventing metabolic disorders linked to excess iron.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Health
Background:
- Excess iron generates reactive oxygen species (ROS) via the Fenton reaction, leading to oxidative stress.
- Oxidative stress contributes to metabolic syndromes like dyslipidemia, hypertension, and type 2 diabetes (T2D).
- Natural antioxidants are being explored to mitigate iron-induced oxidative damage.
Purpose of the Study:
- To investigate the protective effects of ferulic acid (FA) and ferulic acid 4-O-sulfate disodium salt (FAS) against iron-induced oxidative stress.
- To examine the impact of FA and FAS on pancreatic cells (MIN6) and mouse pancreas.
- To elucidate the underlying antioxidant activation mechanism.
Main Methods:
- Iron overload induced in MIN6 cells using ferric ammonium citrate (FAC) and 8-hydroxyquinoline (8HQ).
- Iron overload induced in BALB/c mice using iron dextran (ID).
- Assays included MTT for cell viability, H2DCF for ROS, ICP-MS for iron, and kits for glutathione, SOD, lipid peroxidation, and mRNA expression.
Main Results:
- FA and FAS enhanced cell viability in iron-overloaded MIN6 cells dose-dependently.
- Treatment with FA or FAS reduced ROS levels, glutathione depletion, and lipid peroxidation in iron-exposed cells.
- FA and FAS treatment increased Nrf2 gene levels and downstream antioxidant genes (HO-1, NQO1, GCLC, GPX4) in the mouse pancreas.
Conclusions:
- Ferulic acid (FA) and its metabolite (FAS) demonstrate significant protective effects against iron-induced oxidative damage.
- These phenolic acids activate the Nrf2 antioxidant pathway, upregulating key antioxidant genes.
- FA and FAS show potential as therapeutic agents for conditions associated with iron overload and oxidative stress.
