Modulation of hexavalent chromium-induced genotoxic damage in peripheral blood of mice by epigallocatechin-3-gallate (EGCG) and its relationship to the apoptotic activity

Abstract

This study was conducted to investigate the relationship between modulation of genotoxic damage and apoptotic activity in Hsd:ICR male mice treated with (-)-epigallocatechin-3-gallate (EGCG) and hexavalent chromium [Cr(VI)]. Four groups of 5 mice each were treated with (i) control vehicle only, (ii) EGCG (10 mg/kg) by gavage, (iii) Cr(VI) (20 mg/kg of CrO3) intraperitoneally (ip), and (iv) EGCG in addition to CrO3 (EGCG-CrO3). Genotoxic damage was evaluated by examining presence of micronucleated polychromatic erythrocytes (MN-PCE) obtained from peripheral blood of the caudal vein at 0, 24, 48, and 72 h after treatment. Induction of apoptosis and cell viability were assessed by differential acridine orange/ethidium bromide (AO/EB) staining. EGCG treatment produced no significant changes in frequency of MN-PCE. However, CrO3 treatment significantly increased number of MN-PCE at 24 and 48 h post injection. Treatment with EGCG prior to CrO3 injection decreased number of MN-PCE compared to CrO3 alone. The MN-PCE reduction was greater than when EGCG was administered ip. The frequency of early apoptotic cells was elevated at 48 h following EGCG, CrO3, or EGCG-CrO3 exposure, with highest levels observed in the combined treatment group, while the frequencies of late apoptotic cells and necrotic cells were increased only in EGCG-CrO3 exposure. Our findings support the view that EGCG is protective against genotoxic damage induced by Cr(VI) and that apoptosis may contribute to elimination of DNA-damaged cells (MN-PCE) when EGCG was administered prior to CrO3. Further, it was found that the route of administration of EGCG plays an important role in protection against CrO3-induced genotoxic damage.

The Role of Vitamin C in the Protection and Modulation of Genotoxic Damage Induced by Metals Associated with Oxidative Stress

“…This proposal is consistent with our results since the frequencies of apoptotic cells (particularly, late apoptotic cells) indeed increased signiicantly with the administration of vitamin C, and their administration prior to treatment of V 2 O 5 increased them even further [8]. Additionally, other studies have reported that the apoptosis-inducing activity of antioxidants might be synergistically enhanced by a combined treatment with chemopreventive [44] or genotoxic agents [40]. Therefore, it is plausible that enhanced induction of apoptosis following a combined treatment may positively contribute to the elimination of the cells with V 2 O 5 -induced DNA damage (MN-PCE).…”

“…This was probably because the vitamin C acted as a potent antioxidant (reducing agent) that scavenged free radicals of reactive oxygen and nitrogen species and prevented them from damaging nucleic acids [27,37]. Interestingly, the MN-PCE decrease we observed with vitamin C was more efective than with the administration of beverages with high levels of antioxidants such as green tea [38], red wine [39] and their antioxidant components such as polyphenols [40][41][42].…”

The Role of Green Tea Polyphenols in the Protection from Hexavalent Chromium-Induced Genotoxic Damage

“…Some catechins, including EGCG, possess an esterified gallate moiety at the third position of the C ring, the catechol group on the B ring and the OH groups at the fifth and seventh positions on the A ring (Figure 2 II). The potential free radical scavenging activity of EGCG has been attributed to the presence of the gallate group [10,27].…”

“…The high mobility, solubility and bioavailability of Cr(VI) compounds increase risk in human populations [36,[43][44][45][46]. There are three ways in which Cr(VI) could induce effects on human health: first, by the generation of •OH (oxidative stress); second, by the modification of antioxidant enzymes like SOD, CAT and peroxidase (POX) [10,36,46]; and finally, by the intervention of non-oxidative mechanisms of Cr(VI) [47].…”

“…In the last part of the twentieth century, interest in food polyphenols has increased due to activities such as free radical scavenging, modulation of signal transduction and metal chelation, as well as anti-inflammatory, anti-microbial and anti-proliferation activities [9][10][11]. In addition, polyphenols may exert an indirect antioxidant effect by protecting endogenous antioxidant enzymes in the human body [12].…”