In Vivo Effects of Vanadium Pentoxide and Antioxidants (Ascorbic Acid and Alpha‐Tocopherol) on Apoptotic, Cytotoxic, and Genotoxic Damage in Peripheral Blood of Mice

Abstract

This study was conducted to investigate the effects of vanadium pentoxide (V2O5), ascorbic acid (AA), and alpha-tocopherol (α-TOH) on apoptotic, cytotoxic, and genotoxic activity. Groups of five Hsd:ICR mice were treated with the following: (a) vehicle, distilled water; (b) vehicle, corn oil; (c) AA, 100 mg/kg intraperitoneally (ip); (d) α-TOH, 20 mg/kg by gavage; (e) V2O5, 40 mg/kg by ip injection; (f) AA + V2O5; and (g) α-TOH + V2O5. Genotoxic damage was evaluated by examining micronucleated polychromatic erythrocytes (MN-PCE) obtained from the caudal vein at 0, 24, 48, and 72 h after treatments. Induction of apoptosis and cell viability were assessed at 48 h after treatment in nucleated cells of peripheral blood. Treatment with AA alone reduced basal MN-PCE, while V2O5 treatment marginally increased MN-PCE at all times after injection. Antioxidants treatments prior to V2O5 administration decreased MN-PCE compared to the V2O5 group, with the most significant effect in the AA + V2O5 group. The apoptotic cells increased with all treatments, suggesting that this process may contribute to the elimination of the cells with V2O5-induced DNA damage (MN-PCE). The necrotic cells only increased in the V2O5 group. Therefore, antioxidants such as AA and α-TOH can be used effectively to protect or reduce the genotoxic effects induced by vanadium compounds like V2O5.

Genistein and Ascorbic Acid Reduce Oxidative Stress-Derived DNA Damage Induced by the Antileishmanial Meglumine Antimoniate

“…Our data also revealed that ascorbic acid was able to reduce meglumine antimoniate-induced genomic damage, corroborating previous studies that observed a protective effect of ascorbic acid against mutagenic damage induced by other stressors such as cyclophosphamide (44), arsenic trioxide (45), 3,5-dimethylaminophenol (46), and vanadium pentoxide (47). Ascorbic acid is a nonenzymatic antioxidant obtained from the diet and is essential to humans due to its participation in several physiological activities (48).…”

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

“…Therefore, it has been proposed that the chemopreventive properties of antioxidants are related to their ability to target speciic cellular signaling pathways that regulate cellular proliferation and apoptosis [43]. 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].…”

“…Additionally, the promising low costs of vanadium-based drugs make it particularly atractive, and the ability to overcome the adverse efects of vanadium compounds during therapeutic action is an urgent and crucial issue for its future use in medicine [49]. Our indings strongly suggest that vitamin C can be used efectively in therapy either alone (antioxidant) or in combination with other agents such as V 2 O 5 to reduce their genotoxicity [8].…”

“…In a previous study, we observed that the frequency of micronuclei in polychromatic erythrocytes (MN-PCE) increased with the administration of 40 mg/kg of V 2 O 5 through ip [8], consistent with other studies testing soluble vanadium compounds (Na 3 VO 4 , SVO 5, and NH 4 VO 3 ) [34][35][36]. However, the in vivo administration of vitamin C prior to the V 2 O 5 injection decreased MN-PCE formation compared to administering V 2 O 5 alone, reducing basal MN-PCE, and presenting the strongest protection against genotoxic damage induced by V 2 O 5 .…”

“…However, these efects can be inluenced by the action of low molecular weight antioxidants such as vitamin C, which is capable of chelating metal ions, reducing their catalytic activity, and resulting ROS formation. Since the genotoxicity of heavy metals associated with oxidative stress is based on the oxidative mechanism during reduction [5], vitamin C can be used efectively to protect or reduce the induced genotoxic efects by suppressing oxidative stress caused by these metallic compounds [6][7][8]. However, paradoxically under certain conditions (i.e., low concentration in vitro and the presence of metal ions), vitamin C can exert a pro-oxidant efect, increasing oxidative damage to lipids, DNA and protein, besides being a potential direct or indirect modulator of gene expression [9].…”