ArticleBMC complementary and alternative medicine2011
Ascorbic acid partly antagonizes resveratrol mediated heme oxygenase-1 but not paraoxonase-1 induction in cultured hepatocytes - role of the redox-regulated transcription factor Nrf2.
Article in BMC complementary and alternative medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 219 citations in OpenAlex.
- The Search for Dietary Supplements to Elevate or Activate Circulating Paraoxonases.International journal of molecular sciences · 2017Pooled it
- PON1 and Mediterranean Diet.Nutrients · 2015Pooled it
- Oxidative stress and inflammation in neurodegenerative disorders.Archives of toxicology · 2026Review
- Modulating nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in liver-brain axis disorders.World journal of psychiatry · 2025Review
- Nrf2 Signaling Pathway as a Key to Treatment for Diabetic Dyslipidemia and Atherosclerosis.International journal of molecular sciences · 2024Review
- Expected and Unexpected Effects of Pharmacological Antioxidants.International journal of molecular sciences · 2023Review
- Natural Nrf2 Inhibitors: A Review of Their Potential for Cancer Treatment.International journal of biological sciences · 2023Review
- Antioxidative and Anti-Inflammatory Activity of Ascorbic Acid.Antioxidants (Basel, Switzerland) · 2022Review
- The Relationship between Cancer and Paraoxonase 1.Antioxidants (Basel, Switzerland) · 2022Review
- Perspectives on the Clinical Development of NRF2-Targeting Drugs.Handbook of experimental pharmacology · 2021Review
- Dysregulation of NRF2 in Cancer: from Molecular Mechanisms to Therapeutic Opportunities.Biomolecules & therapeutics · 2018Review
- The Role of the Nrf2/ARE Antioxidant System in Preventing Cardiovascular Diseases.Diseases (Basel, Switzerland) · 2016Review
- Vitamin C treatment attenuates hemorrhagic shock related multi-organ injuries through the induction of heme oxygenase-1.BMC complementary and alternative medicine · 2014Article
- Biomarkers of oxidative stress, antioxidant defence and inflammation are altered in the senescence-accelerated mouse prone 8.Age (Dordrecht, Netherlands) · 2013Article
- Dimethyl fumarate modulation of immune and antioxidant responses: application to HIV therapy.Critical reviews in immunology · 2013Review
- Osteopontin increases heme oxygenase-1 expression and subsequently induces cell migration and invasion in glioma cells.Neuro-oncology · 2012Article
- Do polyphenols enter the brain and does it matter? Some theoretical and practical considerations.Genes & nutrition · 2012Article
- Role of nuclear factor (erythroid-derived 2)-like 2 in metabolic homeostasis and insulin action: A novel opportunity for diabetes treatment?World journal of diabetes · 2012Article
- Dietary oxidized fat activates the oxidative stress-responsive transcription factors NF-κB and Nrf2 in intestinal mucosa of mice.European journal of nutrition · 2011Article
- Hormetics: dietary triggers of an adaptive stress response.Pharmaceutical research · 2011Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBoth resveratrol and vitamin C (ascorbic acid) are frequently used in complementary and alternative medicine. However, little is known about the underlying mechanisms for potential health benefits of resveratrol and its interactions with ascorbic acid.
methodsThe antioxidant enzymes heme oxygenase-1 and paraoxonase-1 were analysed for their mRNA and protein levels in HUH7 liver cells treated with 10 and 25 μmol/l resveratrol in the absence and presence of 100 and 1000 μmol/l ascorbic acid. Additionally the transactivation of the transcription factor Nrf2 and paraoxonase-1 were determined by reporter gene assays.
resultsHere, we demonstrate that resveratrol induces the antioxidant enzymes heme oxygenase-1 and paraoxonase-1 in cultured hepatocytes. Heme oxygenase-1 induction by resveratrol was accompanied by an increase in Nrf2 transactivation. Resveratrol mediated Nrf2 transactivation as well as heme oxygenase-1 induction were partly antagonized by 1000 μmol/l ascorbic acid.
conclusionsUnlike heme oxygenase-1 (which is highly regulated by Nrf2) paraoxonase-1 (which exhibits fewer ARE/Nrf2 binding sites in its promoter) induction by resveratrol was not counteracted by ascorbic acid. Addition of resveratrol to the cell culture medium produced relatively low levels of hydrogen peroxide which may be a positive hormetic redox-signal for Nrf2 dependent gene expression thereby driving heme oxygenase-1 induction. However, high concentrations of ascorbic acid manifold increased hydrogen peroxide production in the cell culture medium which may be a stress signal thereby disrupting the Nrf2 signalling pathway.
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