Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: protective effect of folic acid.

We have previously demonstrated that acute hyperhomocysteinemia induces oxidative stress in rat brain. In the present study, we initially investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative damage, namely total radical-trapping antioxidant potential and activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), as well as on DNA damage in parietal cortex and blood of rats. We also evaluated the effect of folic acid on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of Hcy (0.3-0.6 micromol/g body weight), and/or folic acid (0.011 micromol/g body weight) from their 6th to their 28th day of life. Twelve hours after the last injection the rats were sacrificed, parietal cortex and total blood was collected. Results showed that chronic homocysteine administration increased DNA damage, evaluated by comet assay, and disrupted antioxidant defenses (enzymatic and non-enzymatic) in parietal cortex and blood/plasma. Folic acid concurrent administration prevented homocysteine effects, possibly by its antioxidant and DNA stability maintenance properties. If confirmed in human beings, our results could propose that the supplementation of folic acid can be used as an adjuvant therapy in disorders that accumulate homocysteine.

Influence of orange juice in the levels and in the genotoxicity of iron and copper.

World consumption of natural juices is increasing as a consequence of the human search for a healthier life. The juice production industry, especially for orange juice, is expanding in several countries and particularly in Brazil. Despite scientific data reporting beneficial properties derived from juice consumption, some components of juices have been identified as mutagenic or carcinogenic. Carcinogenic or genotoxic effects may be mediated by the interaction of juice components with transition metals or by sub-products of juice auto-oxidation. In this study, the mutagenic potential of orange juice and two metallic agents used in dietary supplementation, FeSO(4) and CuSO(4), were investigated using the comet assay in mouse blood cells (in vivo). Both metal compounds were genotoxic for eukaryotic cells after 24h treatment at the doses used. Significant damage repair was observed after 48h of treatment with the same compounds. Orange juice had a modulating effect on the action of metallic sulfates. In the case of iron treatment, the presence of the orange juice had a preventive, but not restorative, effect. On the other hand, in the case of copper treatment, the effects were both preventive and restorative. PIXE (particle induced X-ray emission) 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.

Cashew (Anacardium occidentale) apple juice lowers mutagenicity of aflatoxin B1 in S. typhimurium TA102

Cashew (Anacardium occidentale) is a medicinal plant native to Brazil and also yields a nutritious fruit juice. Its large pulpy pseudo-fruit, referred to as the cashew apple, contains high concentrations of vitamin C, carotenoids, phenolic compounds and minerals. Natural and processed cashew apple juice (CAJ/cajuina) are amongst the most popular juices in Brazil, especially in the north-east. Both juices have antioxidant potential and suppress mutagenicity of hydrogen peroxide. In the present study we evaluated the inhibitory effects of CAJ/cajuina on Aflatoxin B1(AFB1)-induced mutation, using the Salmonella/microsome assay with the experimental approaches of pre-, co- and post-treatments. Both CAJ/cajuina suppress AFB1-induced mutagenesis in strain TA102 when applied in co- and in post-treatment. Possible mechanisms for anti-mutagenicity in co-treatment are (a) interaction with S9 enzymes, (b) metabolization to non-mutagenic compounds of AFB1 or (c) inactivation of S9 potential. Total suppression of AFB1 mutagenicity was observed in co-treatment with both CAJ and cajuina. Post-treatment anti-mutagenicity of both juices suggests a modulation of activity of error-prone DNA repair. CAJ/cajuina may be considered promising candidates for control of genotoxicity of AFB1 and may thus be considered as health foods with anti-carcinogenic potential. This promising characteristic warrants further evaluation with in vivo studies.