Betanin, a beetroot component, induces nuclear factor erythroid-2-related factor 2-mediated expression of detoxifying/antioxidant enzymes in human liver cell lines

Abstract

Our recent study has shown that beetroot juice protects against N-nitrosodimethylamine (NDEA)-induced liver injury and increases the activity of phase II enzymes, suggesting the activation of the nuclear factor erythroid-2-related factor 2 (Nrf2) -antioxidant response element (ARE) pathway. The aim of the present study was to further explore the mechanism of the activity of beetroot by evaluating the cytoprotective effects of its major component. The influence of betanin (BET) on the activation of Nrf2 and the expression of GSTA, GSTP, GSTM, GSTT, NQO1 and HO-1 was assessed in two hepatic cell lines: non-tumour THLE-2 and hepatoma-derived HepG2 cell lines. The level of the tumour suppressor p53 in both cell lines and the methylation of GSTP in HepG2 cells were also evaluated. Treatment of both cell lines with 2, 10 and 20 mM of BET resulted in the translocation of Nrf2 from the cytosol to the nucleus. The mRNA and nuclear protein levels of Nrf2 and the binding of Nrf2 to ARE sequences were increased only in the THLE-2 cells and were accompanied by the phosphorylation of serine/threonine kinase (AKT), c-Jun N-terminal kinase ( JNK) and extracellular signal-regulated kinase (ERK). BET also significantly increased the mRNA and protein levels of GSTP, GSTT, GSTM and NQO1 in these cells. Conversely, besides the translocation of Nrf2 from the cytosol to the nucleus, BET did not modulate any of the other parameters measured in the HepG2 cells. BET did not change the methylation of GSTP1 in these cells either. These results indicate that BET through the activation of Nrf2 and subsequent induction of the expression of genes controlled by this factor may exert its hepatoprotective and anticarcinogenic effects. Moreover, the activation of mitogen-activated protein kinases may be responsible for the activation of Nrf2 in the THLE-2 cells.

Beetroot (Beta vulgarisL.) Extract Ameliorates Gentamicin-Induced Nephrotoxicity Associated Oxidative Stress, Inflammation, and Apoptosis in Rodent Model

“…Our findings in in vitro antioxidant assay (DPPH) showed a potent antioxidant activity, which further supports its radical scavenging activity. The observed antioxidant and renal protective effect is considered to be related to the phytoconstituents of beetroot such as betalains, terpenoids, sugars, phenolics, and ascorbic acid [10, 53–55]. All these constituents are known to reduce lipid peroxidation and prevent necrosis which protected the kidney tissue against the oxidative damage and nephrotoxic effect caused by GM treatment [1, 56, 57].…”

Plant Betalains: Safety, Antioxidant Activity, Clinical Efficacy, and Bioavailability

“…Although the cytotoxic effect varies with cell type and duration of exposure (Table ), these reports should be taken into consideration while deciding on dosages for assays involving indicaxanthin. Betacyanins (upto 100 μmol/L) are generally nontoxic when proliferating cell cultures are exposed to it for 24 h or longer (Gentile and others ; Lin and others ; Khan and others ; Nowacki and others ), in case of non‐tumor cells (Krajka‐Kuźniak and others ), but recently cyctotoxicity of betanin concentrations above 25 μmol/L was observed against hepatoma and adenoma cells (Krajka‐Kuźniak and others ; Esatbeyoglu and others ). Furthermore, toxicity of betacyanin fraction from R. humilis berry (IC 50 31 μmol/L) (Khan and others ) or betanin from red beet (IC 50 360 μmol/L (Lee and others ) or 200 μmol/L (Krajka‐Kuźniak and others ) to HepG2 cell cultures has been observed after prolonged exposure.…”

Effects of Beetroot Juice on Recovery of Muscle Function and Performance between Bouts of Repeated Sprint Exercise

“…The most potent antioxidant molecules in BTJ are thought to be the betalain pigments, which are responsible for beetroot’s violet colour [28]. The betalains, and betanin in particular, are very effective electron donors that have been shown to not only attenuate ROS mediated injury but also to upregulate endogenous antioxidant enzymes and stimulate host defence [29,30,31,32]. In addition, BTJ is rich in nitrate, which, via its reduction to nitric oxide (NO) might have indirect antioxidant effects by supressing the accumulation of leukocytes [33], which are thought to be the main producers of ROS after muscle-damaging exercise [34].…”