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

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.

Resveratrol affects the lipid profile but not antioxidant enzymes gene expression in rats fed hypercholesterolaemic diet

“…Rocha et al (2009) showed higher activity of SOD, catalase or superoxide dismutase in liver of rats fed a high fat diet in presence of RSV (1 mg · kg -1 body weight per day). It was also reported that RSV in human hepatoma cells (HUH7) and in rats induces the HO-1 enzyme (Wagner et al, 2011). This was not confirmed in our study.…”

Role of nuclear factor (erythroid-derived 2)-like 2 in metabolic homeostasis and insulin action: A novel opportunity for diabetes treatment?

“…However, this approach is questionable because of the experimental observation that exogenous supplement antioxidants, such as vitamin C, do not generate effective and consistent results for the control of glucose level and diabetic complications [81][82][83] . A potential problem of longterm vitamin C administration with its suppressing effect on the endogenous Nrf2 system [84] , therefore, is unable to produce sufficient antioxidant function. The utilization of Nrf2 activator may provide additional advantages compared with external antioxidant intake to treat oxidative stress and prove the effectiveness of this strategy [81] .…”

Controlled Release of Dexamethasone in PCL/Silk Fibroin/Ascorbic Acid Nanoparticles for the Initiation of Adipose Derived Stem Cells into Osteogenesis

“…In addition to extracellular matrix (ECM) synthesis, AA regulates the differentiation of multi-potent precursor cells into bone cells by stimulation of integrin signalling and supporting cell matrix interaction [20]. The use of AA as an inducer of osteoblast differentiation would be an advantage in the treatment of bone-related diseases [21]. Dexamethasone (DM) is a synthetic steroidal anti-inflammatory drug which has been shown to induce osteogenic differentiation of MSCs in combination with ascorbate-2-phosphate and β-glycerophosphate [22].…”