This study was conducted to investigate the modulating effects of green tea polyphenols on genotoxic damage and apoptotic activity induced by hexavalent chromium [Cr (VI)] in CD-1 mice. Animals were divided into the following groups: (i) injected with vehicle; (ii) treated with green tea polyphenols (30 mg/kg) via gavage; (iii) injected with CrO3 (20 mg/kg) intraperitoneally; (iv) treated with green tea polyphenols in addition to CrO3. Genotoxic damage was evaluated by examining micronucleated polychromatic erythrocytes (MN-PCEs) obtained from peripheral blood 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. Treatment of green tea polyphenols led to no significant changes in the MN-PCEs. However, CrO3 treatment significantly increased MN-PCEs at 24 and 48 h after injection. Green tea polyphenols treatment prior to CrO3 injection led to a decrease in MN-PCEs compared to the group treated with CrO3 only. The average of apoptotic cells was increased at 48 h after treatment compared to control mice, suggesting that apoptosis could contribute to eliminate the DNA damaged cells induced by Cr (VI). Our findings support the proposed protective effects of green tea polyphenols against the genotoxic damage induced by Cr (VI).

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.

This study was conducted to investigate the modulating effects of (-)-epigallocatechin-3-gallate (EGCG), quercetin, and rutin on the genotoxic damage induced by Cr(VI) in polychromatic erythrocytes of CD-1 mice. The animals were divided into the following groups: (i) vehicle only; (ii) flavonoids (10 mg/kg EGCG, 100 mg/kg quercetin, 625 mg/kg rutin, or 100-625 mg/kg quercetin-rutin); (iii) Cr(VI) (20 mg/kg of CrO3); and (iv) flavonoids concomitantly with Cr(VI). All of the treatments were administered intraperitoneally (i.p.). The genotoxic damage was evaluated based on the number of micronucleated polychromatic erythrocytes (MN-PCE) obtained from the caudal vein 0, 24, 48, and 72 h after treatment. Groups treated with EGCG and quercetin exhibited no significant statistical changes in induction of MN-PCE. However, CrO3 treatment significantly increased MN-PCE induction 24 and 48 h after injection. Treatment with flavonoids prior to CrO3 exposure decreased MN-PCE induction compared with CrO3 only. The magnitudes of the potency of flavonoids were in the following order: rutin (82%) > quercetin (64%) > quercetin-rutin (59%) and EGCG (44%). The group treated with rutin significantly reduced genotoxic damage in mice treated with Cr(VI) (antioxidant effect). However rutin exerted a marginal genotoxic effect when administered alone (pro-oxidant effect). Our findings suggest protective effects of EGCG, quercetin, and rutin against genotoxic damage induced by Cr(VI).

1 The involvement of platelet-activating factor (PAF) in immune complex-induced/polymorphonuclearmediated tissue injury was studied by use of a reverse passive Arthus (RPA) model in the peritoneal cavity of rats. 2 Extravasation of protein-rich plasma, accumulation of polymorphonuclear leukocytes (PMN), and the production of nitric oxide (NO) by resident peritoneal mononuclear phagocytes were assayed. 3 Treatment of rats with either UR-12460 or BB-823, two compounds which possess different chemical structures, but elicit the same antagonistic effect on the PAF receptor, abrogated protein-rich plasma extravasation. In contrast, they did not show any effect on the accumulation of PMN. 4 Inhibition of NO production with both N1-mono methyl-L-arginine and N0-nitro-L-arginine failed to prevent protein-rich plasma extravasation. 5 The production of NO by peritoneal adherent cells following RPA was measured in cells maintained for 2 to 28 h in culture, and it was significantly increased in cells removed as early as 15 min after RPA induction, as compared to controls. 6 Addition of 10 nM PAF to the culture medium reduced the generation of NO by peritoneal cells from RPA rats, whereas this mediator enhanced NO production in cells from naive control animals. 7 Treatment with either UR-12460 or BB-823 prior to the induction of RPA produced an almost complete inhibition of NO production. 8 Assay of nitric oxide synthase activity in cell homogenates from peritoneal cells showed that the activity was due to the inducible form of the enzyme. 9 Study by Northen blotting of mRNA coding for the inducible NO synthase (iNOS) showed transcription at 6 and 18 h after the induction of RPA, which was inhibited in UR-12460-treated rats. 10 These data indicate that PAF is the main mediator of the early plasma leakage observed in RPA, and also that PAF is implicated in the triggering of long-term changes via induction of specific genes, as judged from its ability to promote the expression of iNOS.

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.