Genoprotective Effects of the Green Tea-Derived Polyphenol/Epicatechin Gallate in C6 Astroglial Cells

Abstract

In vitro and in vivo studies have recently reported significant chemopreventive effects of green tea-derived polyphenols in different diseases. However, it remains unclear how such effects could be triggered. In order to elucidate the effects of epicatechin gallate (ECG) in C6 cells, both by itself and against H₂O₂-induced genotoxicity, measurements of DNA strand breaks and chromosome loss were performed. DNA damage was measured by comet and micronucleus assays. The present study shows for the first time how ECG, the major green tea-derived polyphenol, is able to exert dose-dependent genoprotective effects in an H₂O₂-induced toxicity model of C6 astroglial cells. We demonstrate that doses of ECG in a range from 0.1 to 1 μM were able to completely prevent H₂O₂-induced genotoxicity in vitro. In contrast, considerably higher concentrations of ECG (10 μM) were able to reverse previous positive effects in a dose- and time-dependent manner. The same results were confirmed by both comet (F(3,9) = 336,148; P < .001) and micronucleus (F(3,9) = 23,228; P < .001) methods. Together, our data show ECG as a dose-dependent genoprotective compound in C6 astroglial cells. This indicates that small doses of polyphenols included in our diet could have beneficial effects on neural cells, contributing to prevention of oxidative stress-associated brain pathologies. In addition, our data highlight the importance of strictly modulating doses and/or consumption of antioxidant-fortified foods or additional supplements containing such beneficial molecules.

Polyphenols and DNA Damage: A Mixed Blessing

“…Kumar et al [79] found that a combination of ellagic acid with curcumin (25 μM each) caused SBs while the separate compounds had no significant effect. A decrease in (background) SBs with epigallocatechin gallate or epicatechin gallate was reported by Durgo et al [36] at 48 but not 72 h. At more reasonable concentrations, the results are mixed: decreases in UV(B)-induced SBs [70] and cyclobutane pyrimidine dimers [72]; decreases in H 2 O 2 -induced SBs and MN [74]; a decrease in SBs induced by cumene hydroperoxide [75]; but SBs and Fpg-sites increased in tetradecanoyl phorbol acetate (TPA)-stimulated neutrophils [78] and an increase in SBs with ellagic acid in prostate cancer cells was reported by Vanella et al [73] at concentrations of 9 μM in one of the cell lines but higher concentrations in two other lines.…”

Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

“…Transport of iron to mitochondria occurs by two potential mechanisms: [1] Fe 2 + from the cytosolic labile iron pool is transported by low-molecular-weight chaperones for delivery to mitochondria, and [2] Tf-iron containing endosomes transiently fuse with the mitochondria for iron delivery. Within the mitochondria, iron is used for heme or ISC synthesis or stored in mitochondrial ferritin.…”

“…Green tea is high in catechin, a subclass of polyphenols, with epigallocatechin gallate (EGCG) comprising more than two-thirds of the catechin content (459). EGCG has been shown to protect against hydrogen-peroxide-induced toxicity in astroglial cells and to alleviate mitochondrial oxidative stress (2,386,390). There are conflicting opinions on the effect of polyphenols on transcription factor NF-E2-related factor 2 activation that up-regulates ferritin (386,390).…”

Neuroprotective Effects of Tea Against Cadmium Toxicity

“…Tea, a potent antioxidant with metal chelating properties owing to its numerous hydroxyl groups [38,39] has been shown to have neuroprotective effects in a number of neuropathological conditions linked to excitotoxicity and oxidative stress [40]. A few studies have reported significant beneficial effects of plant extracts including tea against metal-induced neurotoxicity [19,41,42,43,44]. However, to the best of our knowledge, this is the first study to compare the protective effects of polyphenol rich tea (Camellia sinensis) and EDTA against Cdinduced neurotoxicity.…”