Búsqueda de sustancias nutraceuticas contenidas en la dieta mediterránea: análisis antigenotoxicológico, tumoricida, de antienvejecimiento y de marcas epigenéticas

La producción del sector hortofrutícola se ve incrementada cada año y, paralelamente, la sociedad actual demanda productos agrícolas de calidad. Esta calidad debe ser medida no sólo en un mejor sabor sino en sus potenciales efectos saludables. La dieta mediterránea es una dieta altamente valorada a nivel mundial debido a su alto contenido en antioxidantes naturales presentes en las matrices alimenticias que la constituyen como son las frutas y verduras entre otras (Visioli and Galli 2001; Oh et al. 2005; Saura-Calixto and Goñi 2006). Esta dieta es muy similar a la dieta de nuestros antepasados paleolíticos (Konner and Eaton 2010) y numerosos estudios multidisciplinares han mostrado los efectos positivos de esta dieta frente a enfermedades degenerativas como el cáncer, obesidad, diabetes y enfermedades cardiovasculares (Agarwal and Rao 2000; La Vecchia 2004; Salas-Salvadó et al. 2011; Estruch et al. 2013); además se le ha atribuido una asociación directa con la longevidad (Shahar and Itamar Grotto 2006)

Nutraceutic Potential of Two Allium Species and Their Distinctive Organosulfur Compounds: A Multi-Assay Evaluation

This study aimed to evaluate the biological activities of two Allium species (garlic and onion) as well as diallyl disulphide (DADS) and dipropyl disulphide (DPDS) as their representative bioactive compounds in a multi-assay experimental design. The genotoxic, antigenotoxic, and lifespan eects of garlic, onion, DADS, and DPDS were checked in Drosophila melanogaster and their cytotoxic, pro-apoptotic, and DNA-clastogenic activities were analyzed using HL60 tumoral cells. All compounds were non-genotoxic and antigenotoxic against H2O2-induced DNA damage with a positive dose-response effect and different inhibition percentages (the highest value: 95% for DADS) at all tested concentrations. Daily intake of Allium vegetables, DADS, or DPDS had no positive effects on flies’ lifespan and health span. Garlic and DADS exerted the highest cytotoxic effects in a positive dose-dependent manner. Garlic and DADS exerted a DNA-internucleosomal fragmentation as an index of induced proapoptotic activity on HL60 cells. Allium vegetables and DADS were able to induce clastogenic strand breaks in the DNA of HL60 cells. This study showed the genomic safety ofthe assayed substances and their protective genetic effects against the hydrogen peroxide genotoxine. Long-term treatments during the whole life of the Drosophila genetic model were beneficial only at low-median concentrations. The chemo-preventive activity of garlic could be associated with its distinctive organosulfur DADS. We suggest that supplementary studies are needed to clarify the cell death pathway against garlic and DADS.Fil: Fernández Bedmar, Zahira Noemí. Universidad de Córdoba; EspañaFil: Demyda Peyrás, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Merinas Amo, Tania. Universidad de Córdoba; EspañaFil: del Río Celestino, Mercedes. Laboratorio agroalimentario; Españ

Nutraceutic Potential of Two Allium Species and Their Distinctive Organosulfur Compounds: A Multi-Assay Evaluation

This study aimed to evaluate the biological activities of two Allium species (garlic and onion) as well as diallyl disulphide (DADS) and dipropyl disulphide (DPDS) as their representative bioactive compounds in a multi-assay experimental design. The genotoxic, antigenotoxic, and lifespan effects of garlic, onion, DADS, and DPDS were checked in Drosophila melanogaster and their cytotoxic, pro-apoptotic, and DNA-clastogenic activities were analyzed using HL60 tumoral cells. All compounds were non-genotoxic and antigenotoxic against H2O2-induced DNA damage with a positive dose-response effect and different inhibition percentages (the highest value: 95% for DADS) at all tested concentrations. Daily intake of Allium vegetables, DADS, or DPDS had no positive effects on flies’ lifespan and health span. Garlic and DADS exerted the highest cytotoxic effects in a positive dose-dependent manner. Garlic and DADS exerted a DNA-internucleosomal fragmentation as an index of induced proapoptotic activity on HL60 cells. Allium vegetables and DADS were able to induce clastogenic strand breaks in the DNA of HL60 cells. This study showed the genomic safety of the assayed substances and their protective genetic effects against the hydrogen peroxide genotoxine. Long-term treatments during the whole life of the Drosophila genetic model were beneficial only at low-median concentrations. The chemo-preventive activity of garlic could be associated with its distinctive organosulfur DADS. We suggest that supplementary studies are needed to clarify the cell death pathway against garlic and DADS

Physicochemical Characterization and Biological Activities of Black and White Garlic: In Vivo and In Vitro Assays

White and three types of black garlic (13, 32, and 45 days of aging, named 0C1, 1C2, and 2C1, respectively) were selected to study possible differences in their nutraceutic potential. For this purpose, garlic were physicochemically characterized (Brix, pH, aW, L, polyphenol, and antioxidant capacity), and both in vivo and in vitro assays were carried out. Black garlic samples showed higher polyphenol content and antioxidant capacity than the white ones. The biological assays showed that none of the samples (neither raw nor black garlic) produced toxic effects in the Drosophila melanogaster animal genetic model, nor exerted protective effects against H2O2, with the exception of the 0C1 black garlic. Moreover, only white garlic was genotoxic at the highest concentration. On the other hand, 0C1 black garlic was the most antigenotoxic substance. The in vivo longevity assays showed significant extension of lifespan at some concentrations of white and 0C1and 1C2 black garlic. The in vitro experiments showed that all of the garlic samples induced a decrease in leukemia cell growth. However, no type of garlic was able to induce proapoptotic internucleosomal DNA fragmentation. Taking into account the physicochemical and biological data, black garlic could be considered a potential functional food and used in the preventive treatment of age-related diseases. In addition, our findings could be relevant for black-garlic-processing agrifood companies, as the economical and timing costs can significantly be shortened from 45 to 13 days of aging

Protective Effect of Borage Seed Oil and Gamma Linolenic Acid on DNA: In Vivo and In Vitro Studies

Borage (Borago officinalis L.) seed oil has been used as a treatment for various degenerative diseases. Many useful properties of this oil are attributed to its high gamma linolenic acid content (GLA, 18:3 ω-6). The purpose of this study was to demonstrate the safety and suitability of the use of borage seed oil, along with one of its active components, GLA, with respect to DNA integrity, and to establish possible in vivo toxic and in vitro cytotoxic effects. In order to measure these properties, five types of assays were carried out: toxicity, genotoxicity, antigenotoxicity, cytotoxicity (using the promyelocytic leukaemia HL60 cell line), and life span (in vivo analysis using the Drosophila model). Results showed that i) Borage seed oil is not toxic to D. melanogaster at physiological concentrations below 125 μl/ml and the studies on GLA indicated non-toxicity at the lowest concentration analyzed ii) Borage seed oil and GLA are DNA safe (non-genotoxic) and antimutagenic compared to hydrogen peroxide, thereby confirming its antioxidant capacity; iii) Borage seed oil and GLA exhibited cytotoxic activity in low doses (IC50 of 1 μl/ml and 0.087 mM, respectively) iv) Low doses of borage seed oil (0.19%) increased the health span of D. melanogaster; and v) GLA significantly decreased the life span of D. melanogaster. Based on the antimutagenic and cytotoxic effects along with the ability to increase the health span, we propose supplementation with borage seed oil rather than GLA, because it protects DNA by modulating oxidative genetic damage in D. melanogaster, increases the health span and exerts cytotoxic activity towards promyelocytic HL60 cells. © 2013 Tasset-Cuevas et al.Peer Reviewe

Health and safety in the consumption of B. rapa: A nutraceutical vegetable

Trabajo presentado en el 52nd Congress of the European Societies of Toxicology (EUROTOX 2016), celebrado en Sevilla del 4 al 7 de septiembre de 2016.Current diet is composed by a variety of food adapted to mod- ern living habits. However, recent studies classify some of these meals as undesirable for human health and have produced a grow- ing concern about what we eat and its safety. This is the case of Brassica rapa , a vegetable consumed since antiquity for its whole- some properties but now branded as not recommended due to the toxic effects of some of their constituents. Surprisingly, glucosi- nolate molecules seem to be the responsibles of both effects. In order to elucidate the toxicity of this species, we have selected the in vivo Drosophila melanogaster system as a well proved method to reproduce the human food ingests and the effect of nourish- ment in the genome. With this purpose, three B. rapa accessions selected for their different glucosinolate content were assessed in the Somatic Mutation and Recombination Test (S.M.A.R.T.), as well as gluconapin, the most abundant B. rapa glucosinolate. Our results showeddifferencein B.rapa toxicityrelatedtoitsglucosinolatepro- file and a dose effect-in Drosophila survival after gluconapin oral administration. Also, B. rapa accession with less gluconapin con- tent resulted genotoxic in the S.M.A.R.T. test, contrarily the other accessions which were evaluated as antigenotoxic together with gluconapin. In conclusion, the toxic properties of B. rapa as edible vegetable have been related to the glucosinolate content present in the plant. In this sense, B. rapa accessions with higher gluconapin content exert DNA protection properties and could be recommended for human consumption as safe and healthy.N

Role of Zucchini and Its Distinctive Components in the Modulation of Degenerative Processes: Genotoxicity, Anti-Genotoxicity, Cytotoxicity and Apoptotic Effects

Zucchini (Cucurbita pepo subsp. pepo) is a seasonal vegetable with high nutritional and medical values. Many useful properties of this fruit are attributed to bioactive compounds. Zucchini fruits (“Yellow” and “Light Green” varieties) and four distinctive components (lutein, β-carotene, zeaxanthin and dehydroascorbic acid) were selected. Firstly, the lutein, β-carotene, zeaxanthin and dehydroascorbic acid contents were determined in these fruits. Then, in order to evaluate the safety and suitability of their use, different assays were carried out: (i) genotoxicity and anti-genotoxicity tests to determine the safety and DNA-protection against hydrogen peroxide; (ii) cytotoxicity; and (iii) DNA fragmentation and Annexin V/PI (Propidium Iodide) assays to evaluate the pro-apoptotic effect. Results showed that: (i) all the substances were non-genotoxic; (ii) all the substances were anti-genotoxic except the highest concentration of lutein; (iii) “Yellow” zucchini epicarp and mesocarp exhibited the highest cytotoxic activity (IC50 > 0.1 mg/mL and 0.2 mg/mL, respectively); and (iv) “Light Green” zucchini skin induced internucleosomal DNA fragmentation, β-carotene being the possible molecule responsible for its pro-apoptotic activity. To sum up, zucchini fruit could play a positive role in human health and nutrition due to this fruit and its components were safe, able to inhibit significantly the H2O2-induced damage and exhibit anti-proliferative and pro-apoptotic activities toward HL60 (human promyelocytic leukemia cells) tumor cells. The information generated from this research should be considered when selecting potential accessions for breeding program purposes

Red and White Wine Lees show inhibitory effects on liver carcinogenesis

Scope: Wine has shown anticarcinogenic benefits in hepatocarcinoma and polyphenols seem to be responsible for these effects. Wine lees are the sediments produced during fermentation and they endow wine with organoleptic and physicochemical properties. However, the anticarcinogenic role of these compounds is still unknown. Thus, the purpose of this work is to determine the phytochemical profiles of wine lees and then to analyze their anticarcinogenic effect and DNA methylation on a model of hepatocarcinogenesis. Methods and results: The phytochemical composition of lees is determined by the Folin–Ciocalteu method and high-performance liquid chromatography. An in vivo study using a diethyl nitrosamine-hepatocarcinogenesis-induced model is performed to investigate the hepatoprotective properties of different doses of wine lees. For the DNA methylation analysis, a bisulfite-based method is used. Both types of lees mostly contain pyrogallol, gallic, and syringic acid with a high content of catechins in red lees. The carcinogen hypermethylates the Alu-M2 repetitive sequence and white lees decreases the hypermethylation at all tested concentrations. Low concentration of red and white lees and high concentration of white lees significantly improve the hepatocellular architecture and decrease the mitotic index in the murine model. Conclusion: These findings suggest that wine lees are promising agents for chemoprevention of hepatocarcinoma