Suco de laranja e vitamina C : efeito sobre a estabilidade genômica.

Abstract

Evidence indicates an association between diets rich in fresh fruit and vegetables and a decreased incidence of cancers. Orange juice (OJ) is a food with chemoprotective potential highly relevant for study due to its widespread consumption. OJ is composed of several nutrients and bioactive compounds with antioxidant, antimutagenic, anticarcinogenic and antiathrerogenic activities. Vitamina C (Vit C) is the most abundant nutrient in OJ, and the only one that can be provided in amounts higher that the daily recommended intake by a single portion of OJ (200 mL). Vit C, like other components of OJ, can be either benefical or noxious for biological system, depending of their metabolic context. Indeed, some components of juices have been identified as mutagenic or carcinogenic when isolated. In this study we tested by comet assay in mice in vivo: 1) the genotoxicity of orange juice (OJ) and vitamin C (Vit C); 2) the genotoxicity of FeSO4 and CuSO4: 3) the modulator effect of orange juice and Vit C over genotoxicity of FeSO4 and CuSO4, as well as over methyl methanesulfonate (MMS) and cyclophosphamide (CP). We used the alkaline version of the comet assay to assess DNA damage in peripheral white blood cells of mice. Moreover, the levels of iron and copper in the whole blood and liver of the mice treated with this metals were evaluated by PIXE (Particle-Induced X-ray Emission). Groups of at least 6 mice (half of each gender) were orally given a single dose of either water (control), CP, MMS, FeSO4 or CuSO4. OJ (0.1 mL/Kg) was given either before (pre-treatment) or after (post-treatment) administration of the test substances. Vit C (1 and 30 mg/Kg) was only administered after treatment (post-treatment). DNA damage was evaluated 24 and 48 h after the beginning of the treatment. After 24 h, OJ induced a slight increase in DNA damage and Vit C was genotoxic (30 mg/Kg > 1 mg/Kg). Double treatment with Vit C (at 0 and 24 h) induced a cumulative genotoxic response at 48 h, more intense for the higher dose. FeSO4 and CuSO4 were genotoxic after 24 h and significant DNA damage repair was observed after 48 h of treatment. OJ pre-treatment reduced the genotoxicity of FeSO4 (preventive effect). OJ had a preventive effect over the genotoxicity of CuSO4. OJ post-treatment also reduced the genotoxicity of CuSO4 (restorative effect). OJ had both protective and reparative effects over MMS. OJ had only a reparative effect over CP. Both doses of Vit C enhanced DNA damage caused by FeSO4 and CuSO4. DNA damage caused by MMS was significantly reduced by the lower dose, but not by the higher dose of Vit C. For CP, the DNA damage was not affected by the post-treatment with any of the doses of Vit C. PIXE analysis indicated a positive correlation between DNA damage and the hepatic levels of iron and a negative correlation between whole blood copper and DNA damage. A negative correlation between hepatic iron and whole blood copper content was also seen in the treatment with both ferrous and cupric sulfates. These results point a dynamic interaction between the genotoxicity and the tecidual fate of iron and copper. Vit C and the other components of OJ have several biological effects, including: 1) action as targets for toxicants; 2) influence in drug metabolization/detoxification; and 3) effect in DNA repair and homeostasis. Moreover, Vit C and transition metals, particularly copper and iron, can induce oxidative stress; however, they can also play roles in antioxidant defense system, being a DNA repair modulators. Further data from other treatment schedules are needed to shed light upon the beneficial/noxious effects of OJ as a complex mixture, as well as of its compounds in genomic stability. Indeed, one glass of fresh or adequate processed and stored OJ can be among the options for the daily 5 portions (or even more) of fruits and vegetables recommended for a health and longevity.