[Green tea and its role on chemoprevention in vivo of genotoxic damage induced by carcinogenic metals (chromium [VI])]. / El té verde en la quimioprevención in vivo del daño genotóxico inducido por metales cancerígenos (cromo [VI]).

BACKGROUND: Consumption of green tea, by its antioxidant properties, has been associated with beneficial health effects, because antioxidant may play a role in the risk and pathogenesis of several chronic diseases, especially cardiovascular disease and cancer. On the other hand, it has been reported that metal compounds such as chromium [VI] are carcinogenic and can induce genotoxic damage through the Oxidative Stress. Therefore, it is possible that green tea has a protective effect against the genotoxic damage induced by this compounds. OBJECTIVE: To evaluate the effect of oral administration of green tea over the genotoxic damage induced by Cr [VI] by quantification of micronucleus (MN) in polychromatic erythrocytes (EPC). MATERIALS AND METHODS: We use mice of CD-1 strain that were randomly divided into the following groups: (i) control, (ii) treatment with green tea, (iii) treatment with chromium trioxide, (iv) treatment with green tea and chromium trioxide. The green tea was administrated via intragastric tube every 12 hours over two days (4 doses of 0.25 ml infusions 1.6 g/7.5 ml) and ad libitum (5.6 ml/day for 10 days infusions of 3.2 g/100 ml), while chromium trioxide was administrated via intraperitoneal (20 mg/kg). Blood samples were obtained from the caudal vein, the number of MN in EPC was assessed at 0, 24, 48 and 72 hours after the treatments. RESULTS: The group treated with green tea showed no significant statistical changes in the average of MN. On the other hand, the group that was dosed with the chromium trioxide showed an increase between 4 and 8 MN, which was statistically significant when compared with control group, which confirmed the genotoxic damage. When the green tea treatment was administered before the application of chromium trioxide, there was a decrease in MN frequencies of 31 and 62% at 72 hours, 20 and 35% at 48 hours and 18 and 31% at 24 hours with intragastric and ad libitum respectively, compared with the group treated only with chromium trioxide. Hence, green tea reduced the genotoxic damage induced by chromium trioxide, and the highest protection was presented at 72 hours. CONCLUSIONS: Our findings support the protective effects of green tea against the damage of genetic material, induced by metal compounds such as chromium [VI], suggesting that its antioxidant compounds are those that have a chemopreventive effect on the EOX generated by the Cr [VI] during its reduction to Cr (III). The fact that the largest decrease in the frequency of MN was observed at 72 hours and ad libitum treatment, suggests that, the protective effect depends on the bioavailability, pharmacodynamics and pharmacokinetics of the active ingredient in green tea, so the administration of green tea for a long period of time before the exposure to Cr [VI] could have a more consistent preventive effect.

El té verde en la quimioprevención in vivo del daño genotóxico inducido por metales cancerígenos (cromo [VI]) / Green tea and its role on chemoprevention in vivo of genotoxic damage induced by carcinogenic metals (Chromium [VI])

Introducción: Debido a sus componentes antioxidantes, al consumo de infusiones de té verde se le ha asociado con efectos benéficos para la salud, ya que sus antioxidantes pueden jugar un papel importante en el riesgo y la patogénesis de algunas enfermedades crónicas, como algunos tipos de cáncer y enfermedades cardiovasculares. A su vez, se ha reportado que compuestos metálicos como los del Cr [VI] son carcinogénicos e inducen daño genotóxico mediante Estrés Oxidante (EOx). De ahí que, es posible que el té verde proteja del daño genotóxico inducido por estos compuestos. Objetivo: Se evaluó el efecto de la administración por vía oral del té verde sobre el daño genotóxico inducido por Cr [VI], mediante la cuantificación de micronúcleos (MN) en eritrocitos policromáticos (EPC). Material y método: Ratones de la cepa CD-1 fueron divididos en forma aleatoria en los siguientes grupos: (i) testigo, (ii) tratados con té verde, (iii) tratados con trióxido de cromo, (iv) tratados con té verde y trióxido de cromo. El té verde se administró por sonda intragástrica cada 12 horas durante dos días (4 dosis de 0,25 ml de infusiones de 1,6 g/7,5 ml) y ad libitum 5,6 ml/día durante 10 días de infusiones de 3,2 g/100 ml, mientras que, el trióxido de cromo se aplicó por vía intraperitoneal (20 mg/kg). Se obtuvieron muestras de sangre de la vena caudal, en las que se evaluó el número de MN en EPC a las 0, 24, 48 y 72 horas después de los tratamientos. Resultados: El grupo tratado con té verde no presentó cambios estadísticamente significativos en los promedios de MN. Por su parte, el grupo al que se le administró el trióxido de cromo mostró incrementos entre 4 y 8 MN, que resultaron estadísticamente significativos al compararlos con el grupo testigo, lo que corroboró el daño genotóxico. Cuando se combinaron los tratamientos del té verde y trióxido de cromo se observó una disminución en las frecuencias de MN del 31 y 62% a las 72 horas, del 20 y 35% a las 48 horas y del 18 y 31% a las 24 horas con los tratamientos intragástricos y ad libitum respectivamente, en comparación con el grupo tratado solo con el trióxido de cromo. Por lo que, el té verde redujo el daño genotóxico inducido por el trióxido de cromo, y la mayor protección se presentó a las 72 horas. Conclusiones: Nuestros hallazgos muestran un efecto protector del té verde contra el daño al material genético inducido por compuestos metálicos como los del Cr [VI], sugiriendo que sus componentes antioxidantes son los que tienen un efecto quimiopreventivo sobre el EOx generado por el Cr [VI] durante su reducción a Cr [III]. El hecho de que la mayor disminución de la frecuencia de MN se observe a las 72 horas y con el tratamiento ad libitum, sugiere que el efecto protector depende de la biodisponibilidad, farmacodinámica y farmacocinética del principio activo del té verde, por lo que la administración del té verde durante tiempos más prolongados antes de la exposición con compuestos de Cr [VI] podría tener un efecto preventivo más consistente (AU)

Background: Consumption of green tea, by its antioxidant properties, has been associated with beneficial health effects, because antioxidant may play a role in the risk and pathogenesis of several chronic diseases, especially cardiovascular disease and cancer. On the other hand, it has been reported that metal compounds such as chromium [VI] are carcinogenic and can induce genotoxic damage through the Oxidative Stress. Therefore, it is possible that green tea has a protective effect against the genotoxic damage induced by this compounds. Objective: To evaluate the effect of oral administration of green tea over the genotoxic damage induced by Cr [VI] by quantification of micronucleus (MN) in polychromatic erythrocytes (EPC). Materials and methods: We use mice of CD-1 strain that were randomly divided into the following groups: (i) control, (ii) treatment with green tea, (iii) treatment with chromium trioxide, (iv) treatment with green tea and chromium trioxide. The green tea was administrated via intragastric tube every 12 hours over two days (4 doses of 0.25 ml infusions 1.6 g/7.5 ml) and ad libitum (5.6 ml/day for 10 days infusions of 3.2 g/100 ml), while chromium trioxide was administrated via intraperitoneal (20 mg/kg). Blood samples were obtained from the caudal vein, the number of MN in EPC was assessed at 0, 24, 48 and 72 hours after the treatments. Results: The group treated with green tea showed no significant statistical changes in the average of MN. On the other hand, the group that was dosed with the chromium trioxide showed an increase between 4 and 8 MN, which was statistically significant when compared with control group, which confirmed the genotoxic damage. When the green tea treatment was administered before the application of chromium trioxide, there was a decrease in MN frequencies of 31 and 62% at 72 hours, 20 and 35% at 48 hours and 18 and 31% at 24 hours with intragastric and ad libitum respectively, compared with the group treated only with chromium trioxide. Hence, green tea reduced the genotoxic damage induced by chromium trioxide, and the highest protection was presented at 72 hours. Conclusions: Our findings support the protective effects of green tea against the damage of genetic material, induced by metal compounds such as chromium [VI], suggesting that its antioxidant compounds are those that have a chemopreventive effect on the EOX generated by the Cr [VI] during its reduction to Cr (III). The fact that the largest decrease in the frequency of MN was observed at 72 hours and ad libitum treatment, suggests that, the protective effect depends on the bioavailability, pharmacodynamics and pharmacokinetics of the active ingredient in green tea, so the administration of green tea for a long period of time before the exposure to Cr [VI] could have a more consistent preventive effect (AU)