7 research outputs found
Comparative Study Of β-carotene And Microencapsulated β-carotene: Evaluation Of Their Genotoxic And Antigenotoxic Effects
β-Carotene (BC) is one of the natural pigments that is most commonly added to food; however, the utilization of BC is limited due to its instability. Microencapsulation techniques are commonly used because they can protect the microencapsulated material from oxidization. Nevertheless, the properties of the encapsulated compounds must be studied. We compared the antigenotoxic potential of pure and microencapsulated β-carotene (mBC) in Wistar rats. Two doses of BC or mBC (2.5 or 5.0. mg/kg) were administered by gavage over a period of 14. days. The final gavage was followed by an injection of doxorubicin (DXR). After 24. h the animals were euthanized. The micronucleus test results showed that when both mBC and DXR were given, only the higher dose was antigenotoxic. The results of the comet assay show that when given in association with DXR, mBC had protective effects in the liver. The differences between the results obtained with BC and mBC suggest that possibly the carotenoid biodisponibility was modified by the process of microencapsulation. In conclusion, mBC does not lose its protective properties, but higher doses must be used to observe antigenotoxic effects. This is the first time that the genotoxicity and antigenotoxicity of a microencapsulated compound was evaluated in vivo. © 2012 Elsevier Ltd.50514181424Agarwal, S., Rao, A.V., Carotenoids and chronic diseases (2000) Drug Metabol. Drug Interact., 17, pp. 189-210Alija, A.J., Bresgen, N., Sommerburg, O., Siems, W., Eckl, P.M., Cytotoxic and genotoxic effects of beta-carotene breakdown products on primary rat hepatocytes (2004) Carcinogenesis, 25, pp. 827-831Arriaga-Alba, M., Rivera-Sanchez, R., Parra-Cervantes, G., Barro-Moreno, F., Flores-Paz, R., Garcia-Jimenez, E., Antimutagenesis of beta-carotene to mutations induced by quinolone on Salmonella typhimurium (2000) Arch. Med. Res., 31, pp. 156-161Augustin, M.A., Hemar, Y., Nano- and micro-structured assemblies for encapsulation of food ingredients (2009) Chem. Soc. Rev., 38, pp. 902-912Barbosa, M.I.M.J., Borsarelli, C.D., Mercadante, A.Z., Light stability of spray-dried bixin encapsulated with different edible polysaccharide preparations (2005) Food Res. Int., 38, pp. 989-994Bisby, R.H., Morgan, C.G., Hamblett, I., Gorman, A.A., Quenching of singlet oxygen by Trolox C, ascorbate, and amino acids: effects of pH and temperature (1999) J. Phys. Chem. A, 103, pp. 7454-7459Boon, C.S., McClements, D.J., Weiss, J., Decker, E.A., Role of iron and hydroperoxides in the degradation of lycopene in oil-in-water emulsions (2009) J. Agric. Food Chem., 57, pp. 2993-2998Boon, C.S., McClements, D.J., Weiss, J., Decker, E.A., Factors influencing the chemical stability of carotenoids in foods (2010) Crit. Rev. Food Sci. Nutr., 50, pp. 515-532Bowen, D.E., Whitwell, J.H., Lillford, L., Henderson, D., Kidd, D., Mc Garry, S., Pearce, G., Kirkland, D.J., Evaluation of a multi-endpoint assay in rats, combining the bone-marrow micronucleus test, the Comet assay and the flow-cytometric peripheral blood micronucleus test (2011) Mutat. Res./Genet. Toxicol. Environ. Mutagen., 722, pp. 7-19Celik, A., Ogenler, O., Comelekoglu, U., The evaluation of micronucleus frequency by acridine orange fluorescent staining in peripheral blood of rats treated with lead acetate (2005) Mutagenesis, 20, pp. 411-415Davies, B.H., (1976) Chemistry and Biochemistry of Plant Pigments, 2, pp. 38-165. , Academic Press, Londonde Vos, W.M., Castenmiller, J.J.M., Hamer, R.J., Brummer, R.J.M., Nutridynamics - Studying the dynamics of food components in products and in the consumer (2006) Curr. Opin. Biotechnol., 17, pp. 217-225Dhawan, A., Bajpayee, M., Parmar, D., Comet assay: a reliable tool for the assessment of DNA damage in different models (2009) Cell Biol. Toxicol., 25, pp. 5-32Druesne-Pecollo, N., Latino-Martel, P., Norat, T., Barrandon, E., Bertrais, S., Galan, P., Hercberg, S., Beta-carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials (2010) Int. J. Cancer, 127, pp. 172-184Evangelista, C.M.W., Antunes, L.M.G., Francescato, H.D.C., Bianchi, M.L.P., Effects of the olive, extra virgin olive and canola oils on cisplatin-induced clastogenesis in Wistar rats (2004) Food Chem. Toxicol., 42, pp. 1291-1297Faria, A.F., Mignone, R.A., Montenegro, M.A., Mercadante, A.Z., Borsarelli, C.D., Characterization and singlet oxygen quenching capacity of spray-dried microcapsules of edible biopolymers containing antioxidant molecules (2010) J. Agric. Food Chem., 58, pp. 8004-8011Fenech, M., Nutrition and genome health Nutrigenomics - Opportunities in Asia (2007) Forum Nutr., 60, pp. 49-65Ferreira, A.L.A., Salvadori, D.M.F., Nascimento, M.C.M.O., Rocha, N.S., Correa, C.R., Pereira, E.J., Matsubara, L.S., Ladeira, M.S.P., Tomato-oleoresin supplement prevents doxorubicin-induced cardiac myocyte oxidative DNA damage in rats (2007) Mutat. Res./Genet. Toxicol. Environ. Mutagen., 631, pp. 26-35Gharsallaoui, A., (2008), Microencapsulation of food ingredients by spray-drying, in: SciTopics (Ed.), SciTopics. SciTopicsGradecka-Meesters, D., Palus, J., Prochazka, G., Segerbäck, D., Dziubałtowska, E., Kotova, N., Jenssen, D., Stepnik, M., Assessment of the protective effects of selected dietary anticarcinogens against DNA damage and cytogenetic effects induced by benzo[a]pyrene in C57BL/6J mice (2011) Food Chem. Toxicol., 49, pp. 1674-1683Hayashi, M., Sofuni, T., Morita, T., Simulation study of the effects of multiple treatments in the mouse bone marrow micronucleus test (1991) Mutat. Res., 252, pp. 281-287Hayashi, M., MacGregor, J.T., Gatehouse, D.G., Adler, I.D., Blakey, D.H., Dertinger, S.D., Krishna, G., Sutou, S., In vivo rodent erythrocyte micronucleus assay (2000) II. Some aspects of protocol design including repeated treatments, integration with toxicity testing, and automated scoring. Environ. Mol. Mutagen., 35, pp. 234-252Krinsky, N.I., Johnson, E.J., Carotenoid actions and their relation to health and disease (2005) Mol. Aspects Med., 26, pp. 459-516Kuang, S.S., Oliveira, J.C., Crean, A.M., Microencapsulation as a tool for incorporating bioactive ingredients into food (2010) Crit. Rev. Food Sci. Nutr., 50, pp. 951-968Lissi, E.A., Encinas, M.V., Lemp, E., Rubio, M.A., Singlet oxygen O2(1-Delta-G) bimolecular processes - Solvent and compartmentalization effects (1993) Chem. Rev., 93, pp. 699-723Lu, Q.Y., Hung, J.C., Heber, D., Go, V.L.W., Reuter, V.E., Cordon-Cardo, C., Scher, H.I., Zhang, Z.F., Inverse associations between plasma lycopene and other carotenoids and prostate cancer (2001) Cancer Epidemiol. Biomarkers Prev., 10, pp. 749-756Macgregor, J.T., Heddle, J.A., Hite, M., Margolin, B.H., Ramel, C., Salamone, M.F., Tice, R.R., Wild, D., Guidelines for the conduct of micronucleus assays in mammalian bone-marrow erythrocytes (1987) Mutat. Res., 189, pp. 103-112Maiani, G., Periago Castón, M.J., Catasta, G., Toti, E., Cambrodón, I.G., Bysted, A., Granado-Lorencio, F., Schlemmer, U., Carotenoids: actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans (2009) Mol. Nutr. Food Res., 53, pp. S194-S218Manca, D., Rovaglio, M., Modeling the controlled release of microencapsulated drugs: theory and experimental validation (2003) Chem. Eng. Sci., 58, pp. 1337-1351Mayne, S.T., Handelman, G.J., Beecher, G., Beta-carotene and lung cancer promotion in heavy smokers - A plausible relationship? (1996) J. Natl. Cancer Inst., 88, pp. 1513-1515Mercadante, A.Z., Carotenoids in foods: sources and stability during processing and storage (2008) Food Colorants: Chemical and Functional Properties, pp. 213-240. , CRC Press, Boca Raton, C. Socaciu (Ed.)Montenegro, M.A., Nunes, I.L., Mercadante, A.Z., Borsarelli, C.D., Photoprotection of vitamins in skimmed milk by an aqueous soluble lycopene-gum Arabic microcapsule (2007) J. Agric. Food Chem., 55, pp. 323-329Mukherjee, A., Agarwal, K., Aguilar, M.A., Sharma, A., Anticlastogenic activity [beta]-carotene against cyclophoshamide in mice in vivo (1991) Mutat. Res. Lett., 263, pp. 41-46Muzandu, K., El Bohi, K., Shaban, Z., Ishizuka, M., Kazusaka, A., Fujita, S., Lycopene and beta-carotene ameliorate catechol estrogen-mediated DNA damage (2005) Jpn. J. Vet. Res., 52, pp. 173-184Namitha, K.K., Negi, P.S., Chemistry and biotechnology of carotenoids (2010) Crit. Rev. Food Sci. Nutr., 50, pp. 728-760Nunes, I.L., Mercadante, A.Z., Encapsulation of lycopene using spray-drying and molecular inclusion processes (2007) Braz. Arch. Biol. Technol., 50, pp. 893-900Ostling, O., Johanson, K.J., Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells (1984) Biochem. Biophys. Res. Commun., 123, pp. 291-298Parada, J., Aguilera, J.M., Food microstructure affects the bioavailability of several nutrients (2007) J. Food Sci., 72, pp. R21-R32Prado, S.M., Buera, M.P., Elizalde, B.E., Structural collapse prevents β-carotene loss in a supercooled polymeric matrix (2005) J. Agric. Food Chem., 54, pp. 79-85Ribeiro, J.C., Antunes, L.M.G., Aissa, A.F., Darin, J.D.C., De Rosso, V.V., Mercadante, A.Z., Bianchi, M.D.P., Evaluation of the genotoxic and antigenotoxic effects after acute and subacute treatments with acai pulp (Euterpe oleracea Mart.) on mice using the erythrocytes micronucleus test and the comet assay (2010) Mutat. Res./Genet. Toxicol. Environ. Mutagen., 695, pp. 22-28Rodriguez-Amaya, D.B., Food carotenoids: analysis, composition and alterations during storage and processing of foods (2003) Forum Nutr., 56, pp. 35-37Salvadori, D.M.F., Ribeiro, L.R., Oliveira, M.D.M., Pereira, C.A.B., Becak, W., The protective effect of beta-carotene on genotoxicity induced by cyclophosphamide (1992) Mutat. Res., 265, pp. 237-244Sendao, M.C., Behling, E.B., dos Santos, R.A., Antunes, L.M.G., Bianchi, M.D.L.P., Comparative effects of acute and subacute lycopene administration on chromosomal aberrations induced by cisplatin in male rats (2006) Food Chem. Toxicol., 44, pp. 1334-1339Sies, H., Stahl, W., Sundquist, A.R., Antioxidant functions of vitamins (1992) Ann. NY Acad. Sci., 669, pp. 7-20Singh, N.P., Mccoy, M.T., Tice, R.R., Schneider, E.L., A Simple Technique for Quantitation of Low-Levels of DNA Damage in Individual Cells (1988) Exp. Cell Res., 175, pp. 184-191Singh, M., Kaur, P., Sandhir, R., Kiran, R., Protective effects of vitamin E against atrazine-induced genotoxicity in rats (2008) Mutat. Res./Genet. Toxicol. Environ. Mutagen., 654, pp. 145-149Tweats, D.J., Blakey, D., Heflich, R.H., Jacobs, A., Jacobsen, S.D., Morita, T., Nohmi, T., Tice, R., Report of the IWGT working group on strategy/interpretation for regulatory in vivo tests - II. Identification of in vivo-only positive compounds in the bone marrow micronucleus test (2007) Mutat. Res./Genet. Toxicol. Environ. Mutagen., 627, pp. 92-105Wang, Y., Lu, Z., Wu, H., Lv, F., Study on the antibiotic activity of microcapsule curcumin against foodborne pathogens (2009) Int. J. Food Microbiol., 136, pp. 71-74Wilkinson, F., Helman, W.P., Ross, A.B., Rate constants for the decay and reactions of the lowest electronically excited singlet-state of molecular-oxygen in solution - An expanded and revised compilation (1995) J. Phys. Chem. Ref. Data, 24, pp. 663-1021Yamanushi, T.T., Torii, M.I., Janjua, N., Kabuto, H., In vivo tissue uptake of intravenously injected water soluble all-trans beta-carotene used as a food colorant (2009) Nutr. J., 8Zulueta, A., Esteve, M.J., Frigola, A., Carotenoids and color of fruit juice and milk beverage mixtures (2007) J. Food Sci., 72, pp. C457-C46
Evaluation Of The Genotoxic And Antigenotoxic Effects After Acute And Subacute Treatments With Açai Pulp (euterpe Oleracea Mart.) On Mice Using The Erythrocytes Micronucleus Test And The Comet Assay
Açai, the fruit of a palm native to the Amazonian basin, is widely distributed in northern South America, where it has considerable economic importance. Whereas individual polyphenolics compounds in açai have been extensively evaluated, studies of the intact fruit and its biological properties are lacking. Therefore, the present study was undertaken to investigate the . in vivo genotoxicity of açai and its possible antigenotoxicity on doxorubicin (DXR)-induced DNA damage. The açai pulp doses selected were 3.33, 10.0 and 16.67. g/kg b.w. administered by gavage alone or prior to DXR (16. mg/kg b.w.) administered by intraperitoneal injection. Swiss albino mice were distributed in eight groups for acute treatment with açai pulp (24. h) and eight groups for subacute treatment (daily for 14 consecutive days) before euthanasia. The negative control groups were treated in a similar way. The results of chemical analysis suggested the presence of carotenoids, anthocyanins, phenolic, and flavonoids in açai pulp. The endpoints analyzed were micronucleus induction in bone marrow and peripheral blood cells polychromatic erythrocytes, and DNA damage in peripheral blood, liver and kidney cells assessed using the alkaline (pH >13) comet assay. There were no statistically significant differences (. p>. 0.05) between the negative control and the groups treated with the three doses of açai pulp alone in all endpoints analyzed, demonstrating the absence of genotoxic effects. The protective effects of açai pulp were observed in both acute and subacute treatments, when administered prior to DXR. In general, subacute treatment provided greater efficiency in protecting against DXR-induced DNA damage in liver and kidney cells. These protective effects can be explained as the result of the phytochemicals present in açai pulp. These results will be applied to the developmental of food with functional characteristics, as well as to explore the characteristics of açai as a health promoter. © 2009 Elsevier B.V..6951-22228Lila, M.A., Anthocyanins and human health: an in vitro investigative approach (2004) J. Biomed. Biotechnol., 5, pp. 306-313De Rosso, V.V., Mercadante, A.Z., Identification and quantification of carotenoids, by HPLC-PDA-MS/MS, from Amazonian fruits (2007) J. Agric. Food Chem., 55, pp. 5062-5072Murrieta, R.S.S., Dufour, D., Siqueira, A.D., Food consumption and subsistence in three caboclo populations on Marajo Island, Amazônia, Brazil (1999) Hum. Ecol., 27, pp. 455-475Tinoco, A.C., (2005), Açaí amazônico: novas perspectivas de negócio, Embrapa Amazônia Oriental, Belém, PA, 2005, 1 CD-ROM. Trabalho apresentado no Workshop Regional do Açaizeiro: pesquisa, produção e comercialização, Belém, PAKhayat, T.C., Comportamento do risco para doença aterosclerótica coronária na população de Inhangapí cuja base alimentar é o fruto do açaí (Euterpe oleracea), 2005, Trabalho de Conclusão de Curso. (Graduação em Medicina) - Universidade Federal do Pará, Conselho Nacional de Desenvolvimento Científico e TecnológicoOliveira, M.S.P., Carvalho, J.E.U., (2000), p. 51. , W.M.O. Nascimento, Açaí (Euterpe oleracea Mart.) Jaboticabal: FUNEPPozo-Insfran, D., Brenes, D., Talcott, S.T., Phytochemical composition and pigment stability of Açai (Euterpe oleracea Mart.) (2004) J. Agric. Food Chem., 52, pp. 1539-1545Pozo-Insfran, D., Percival, S.S., Talcott, S.T., Açai (Euterpe oleracea Mart.) polyphenolics in their glycoside and aglycone forms induce apoptosis of HL-60 leukemia cells (2006) J. Agric. Food Chem., 54, pp. 1222-1229De Rosso, V.V., Morán, F.E.V., Mercadante, A.Z., Borsarelli, C.D., Singlet oxygen quenching by anthocyanin's flavylium cations (2008) Free Radic. Res., 42, pp. 885-891Ghosh, D., Sheepens, A., Vascular action of polyphenols (2009) Mol. Nutr. Food Res., 53, pp. 322-331Rocha, A.P., Carvalho, L.C., Sousa, M.A., Madeira, S.V., Sousa, P.J., Tano, T., Schini-Kerth, V.B., Soares de Moura, R., Endothelium-dependent vasodilator effect of Euterpe oleracea Mart. (Açaí) extracts in mesenteric vascular bed of the rat (2007) Vascul. Pharmacol., 46, pp. 97-104Stevenson, D.E., Hurst, R.D., Polyphenolic phytochemicals-just antioxidants or much more? (2007) Cell. Mol. Life Sci., 64, pp. 2900-2916Weiss, R.B., The anthracyclines: will we ever find a better doxorubicin? (1992) Semin. Oncol., 19, pp. 670-686Kaklamani, V.G., Gradishar, W.J., Epirubicin versus doxorubicin: which is the anthracycline of choice for the treatment of breast cancer? (2003) Clin. Breast Cancer, 4, pp. S26-S33Pai, V.B., Nahata, M.C., Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention (2000) Drug Saf., 22, pp. 263-302Islaih, M., Halstead, B.W., Kadura, I.A., Reid-Hubbard, J.L., Flick, F., Altizer, J.L., Thom, D.J., Watson, D.E., Relationships between genomic, cell cycle, and mutagenic responses of TK6 cells exposed to DNA damaging chemicals (2005) Mutat. Res., 578, pp. 100-116Antunes, L.M.G., Takahashi, C.S., Effects of high doses of vitamins C and E against doxorubicin-induced chromosomal damage in Wistar rat bone marrow cells (1998) Mutat. Res., 419, pp. 137-143Antunes, L.M.G., Pascoal, L.M., Bianchi, M.L.P., Dias, F.L., Evaluation of the clastogenicity and anticlastogenicity of the carotenoid bixin in human lymphocyte cultures (2005) Mutat. Res., 585, pp. 113-119Tan, H.H., Porter, A.G., DNA methyltransferase I is a mediator of doxorubicin-induced genotoxicity in human cancer cells (2009) Biochem. Biophys. Res. Commun., 382, pp. 462-467Beillerot, A., Dominguez, J.C., Kirsch, G., Bagrel, D., Synthesis and protective effects of coumarin derivatives against oxidative stress induced by doxorubicin (2008) Bioorg. Med. Chem. Lett., 18, pp. 1102-1105Spada, P.D., de Souza, G.G., Bortolini, G.V., Henriques, J.A., Salvador, M., Mutagenic, and antimutagenic activity of frozen fruits (2008) J. Med. Food, 11, pp. 144-151. , AntioxidantSingleton, V.L., Rossi, J.A., Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents (1965) Am. J. Enol. Vitic., 16, pp. 144-158Zhishen, J., Mengcheng, T., Jianming, W., The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals (1999) Food Chem., 64, pp. 555-559De Rosso, V.V., Mercadante, A.Z., HPLC-PDA-MS/MS of anthocyanins and carotenoids from dovyalis and tamarillo fruits (2007) J. Agric. Food Chem., 55, pp. 9135-9141Prahalathan, C., Selvakumar, E., Varalashmi, P., Kumarasamy, P., Saravanan, R., Salubrious effects of lipoic acid against adriamycin-induced clastogenesis and apoptosis in Wistar rat bone marrow cells (2006) Toxicology, 222, pp. 225-232MacGregor, J.T., Heddle, J.A., Hite, M., Margolin, B.H., Ramel, C., Salamone, M.F., Tia, R.R., Wild, D., Guidelines for the conduct of micronucleus assay in mammalian bone marrow erythrocyte (1987) Mutat. Res., 189, pp. 103-112Hayashi, M., MacGregor, J.T., Gatehouse, D.G., Adler, I.D., Blakey, D.H., Dertinger, S.D., Krishna, G., Sutou, S., In vivo rodent erythrocyte micronucleus assay. II. Some aspects of protocol design including repeated treatments, integration with toxicity testing, and automated scoring (2000) Environ. Mol. Mutagen., 35, pp. 234-252Waters, M.D., Brady, A.L., Stack, H.F., Brockman, H.E., Antimutagenicity profiles for some model compounds (1990) Mutat. Res., 238, pp. 57-85Tice, R.R., Agurell, E., Anderson, D., Burlinson, B., Hartmann, A., Kobayashi, H., Miyamae, Y., Sasaki, Y.F., Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing (2000) Environ. Mol. Mutagen., 35, pp. 206-221Singh, N.P., McCoy, M.T., Tice, R.R., Shneider, E.L., A simple technique for quantitation of low DNA levels of DNA damage in individual cells (1988) Exp. Cell Res., 175, pp. 181-191Collins, A.R., Ma, A.G., Duthie, S.J., The kinetics of repair of oxidative DNA damage (strand breaks and oxidised pyrimidines) in human cells (1995) Mutat. Res., 336, pp. 69-77Antunes, L.M.G., Ara, M.C.P., Mutagenicity and antimutagenicity of the main food colorings (2000) Rev. Nutr., 13, pp. 81-88Zeiger, E., What is needed for an acceptable antimutagenicity manuscript? (2007) Mutat. Res., 626, pp. 1-3Serpeloni, J.M., Bisarro dos Reis, M., Rodrigues, J., Campaner dos Santos, L., Vilegas, W., Varanda, E.A., Dokkedal, A.L., Cólus, I.M., In vivo assessment of DNA damage and protective effects of extracts from Miconia species using the comet assay and micronucleus test (2008) Mutagenesis, 23, pp. 501-507Santos, R.A., Jordão, A.A., Vannucchi, H., Takahashi, C.S., Protection of doxorubicin-induced DNA damage by sodium selenite and selenomethionine in Wistar rats (2007) Nutr. Res., 27, pp. 343-348Takeuchi, P.L., Antunes, L.M.G., Takahashi, C.S., Modulation of doxorubicin-induced clastogenesis in Wistar rat bone marrow cells by vitamin B6 (2008) Arch. Toxicol., 82, pp. 869-873Weijl, N.I., Cleton, F.J., Osanto, S., Free radicals and antioxidants in chemotherapy-induced toxicity (1997) Cancer Treat. Rev., 23, pp. 209-240Conklin, K.A., Cancer chemotherapy and antioxidants (2004) J. Nutr., 134, pp. 3201-3204Simpson, C., Herr, H., Courtville, K.A., Concurrent therapies that protect against doxorubicin-induced cardiomyopathy (2003) Clin. J. Oncol. Nurs., 8, pp. 497-501Andreadou, I., Papaefthimiou, M., Zira, A., Constantinou, M., Sigala, F., Skaltsounis, A.L., Tsantili-Kakoulidou, A., Mikros, E., Metabonomic identification of novel biomarkers in doxorubicin cardiotoxicity and protective effect of the natural antioxidant oleuropein (2009) NMR Biomed., 22, pp. 585-592Preston, R.J., Dean, B.J., Galloway, S., Holden, H., McFee, A.F., Shelby, M.D., Mammalian in vivo cytogenetic assays: analysis of chromosome aberrations in bone marrow cells (1987) Mutat. Res., 189, pp. 157-165Salvadori, D.M., Ribeiro, L.R., Oliveira, M.D., Pereira, C.A., Beçak, W., The protective effect of beta-carotene on genotoxicity induced by cyclophosphamide (1992) Mutat. Res., 265, pp. 237-244Nesslany, F., Zennouche, N., Simar-Meintiéres, S., Talahari, I., Nkili-Mbou, E.N., Marzin, D., In vivo comet assay on isolated kidney cells to distinguish genotoxic carcinogens from epigenetic carcinogens or cytotoxic compounds (2007) Mutat. Res., 630, pp. 28-41Schauss, A.G., Wu, X., Prior, R.L., Ou, B., Patel, D., Huang, D., Kababick, J.P., Phytochemical and nutrient composition of the freeze-dried amazonian palm berry, Euterpe oleracea Mart. (acai) (2006) J. Agric. Food Chem., 54, pp. 8598-8603Azevedo, L., Alves de Lima, P.L., Gomes, J.C., Stringheta, P.C., Ribeiro, D.A., Salvadori, D.M., Differential response related to genotoxicity between eggplant (Solanum melanogena) skin aqueous extract and its main purified anthocyanin (delphinidin) in vivo (2007) Food Chem. Toxicol., 45, pp. 852-858Ghosh, D., Konishi, T., Anthocyanins and anthocyanin-rich extracts: role in diabetes and eye function (2007) Asia Pac. J. Clin. Nutr., 16, pp. 200-208Pacheco-Palencia, L.A., Talcott, S.T., Safe, S., Mertens-Talcott, S., Absorption and biological activity of phytochemical-rich extracts from açai (Euterpe oleracea Mart.) pulp and oil in vitro (2008) J. Agric. Food Chem., 56, pp. 3593-3600Youdim, K.A., Shudit-hale, B., MacKinnon, S., Kalt, W., Joseph, J.A., Polyphenolics enhance red blood cell resistance to oxidative stress: in vitro and in vivo (2000) Biochim. Biophys. Acta, 1523, pp. 117-122Lichtenthäler, R., Rodrigues, R.B., Maia, J.G., Papagiannopoulos, M., Fabricius, H., Marx, F., Total oxidant scavenging capacities of Euterpe oleracea Mart. (Açaí) fruits (2005) Int. J. Food Sci. Nutr., 56, pp. 53-64Talavéra, S., Felgines, C., Texier, O., Besson, C., Gil-Izquierdo, A., Lamaison, J.L., Rémésy, C., Anthocyanin metabolism in rats and their distribution to digestive area, kidney, and brain (2005) J. Agric. Food Chem., 53, pp. 3902-3908Schauss, A.G., Wu, X., Prior, R.L., Ou, B., Huang, D., Owens, J., Agarwal, A., Shanbrom, E., Antioxidant capacity and other bioactivities of the freeze-dried Amazonian palm berry, Euterpe oleracea Mart. (acai) (2006) J. Agric. Food Chem., 54, pp. 8604-8610De Rosso, V.V., Hillebrand, S., Montilla, E.C., Bobbio, F.O., Winterhalter, P., Mercadante, A.Z., Determination of anthocyanins from acerola (Malpighia emarginata DC.) and açai (Euterpe oleracea Mart.) by HPLC-PDA and HPLC-MS (2008) J. Food Compos. Anal., 21, pp. 291-299Mertens-Talcott, S.U., Rios, J., Jilma-Stohlawetz, P., Pacheco-Palencia, L.A., Meibohm, B., Talcott, S.T., Derendorf, H., Pharmacokinetics of anthocyanins and antioxidant effects after the consumption of anthocyanin-rich açai juice and pulp (Euterpe oleracea Mart.) in human healthy volunteers (2008) J. Agric. Food Chem., 56, pp. 7796-780
Diet Carotenoid Lutein Modulates The Expression Of Genes Related To Oxygen Transporters And Decreases Dna Damage And Oxidative Stress In Mice
Lutein (LT) is a carotenoid obtained by diet and despite its antioxidant activity had been biochemically reported, few studies are available concerning its influence on the expression of antioxidant genes. The expression of 84 genes implicated in antioxidant defense was quantified using quantitative reverse transcription polymerase chain reaction array. DNA damage was measured by comet assay and glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were quantified as biochemical parameters of oxidative stress in mouse kidney and liver. cDDP treatment reduced concentration of GSH and increased TBARS, parameters that were ameliorated in treatment associated with LT. cDDP altered the expression of 32 genes, increasing the expression of GPx2, APC, Nqo1 and CCs. LT changed the expression of 37 genes with an induction of 13 mainly oxygen transporters. In treatments associating cDDP and LT, 30 genes had their expression changed with a increase of the same genes of the cDDP treatment alone. These results suggest that LT might act scavenging reactive species and also inducing the expression of genes related to a better antioxidant response, highlighting the improvement of oxygen transport. This improved redox state of the cell through LT treatment could be related to the antigenotoxic and antioxidant effects observed. © 2014 Elsevier Ltd.70205213Anderson, D., Yu, T.W., Phillips, B.J., Schmezer, P., The effect of various antioxidants and other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes in the COMET assay (1994) Mutat. Res., 307, pp. 261-271Andrieu, G., Quaranta, M., Leprince, C., Hatzoglou, A., The GTPase Gem and its partner Kif9 are required for chromosome alignment, spindle length control, and mitotic progression (2012) FASEB J, 26, pp. 5025-5034Astley, S.B., Hughes, D.A., Wright, A.J., Elliott, R.M., Southon, S., DNA damage and susceptibility to oxidative damage in lymphocytes: effects of carotenoids in vitro and in vivo (2004) Br. J. Nutr., 91, pp. 53-61Baqai, F.P., Gridley, D.S., Slater, J.M., Luo-Owen, X., Stodieck, L.S., Ferguson, V., Chapes, S.K., Pecaut, M.J., Effects of spaceflight on innate immune function and antioxidant gene expression (2009) J. Appl. Physiol., 106, pp. 1935-1942Brigelius-Flohe, R., Kipp, A., Glutathione peroxidases in different stages of carcinogenesis (2009) Biochim. Biophys. Acta, 1790, pp. 1555-1568Brigelius-Flohe, R., Kipp, A.P., Physiological functions of GPx2 and its role in inflammation-triggered carcinogenesis (2012) Ann. N.Y. Acad. Sci., 1259, pp. 19-25Brigelius-Flohe, R., Maiorino, M., Glutathione peroxidases (2013) Biochim. Biophys. Acta, 1830, pp. 3289-3303Burmester, T., Weich, B., Reinhardt, S., Hankeln, T., A vertebrate globin expressed in the brain (2000) Nature, 407, pp. 520-523Chew, B.P., Brown, C.M., Park, J.S., Mixter, P.F., Dietary lutein inhibits mouse mammary tumor growth by regulating angiogenesis and apoptosis (2003) Anticancer Res., 23, pp. 3333-3339Collins, A.R., The comet assay for DNA damage and repair: principles, applications, and limitations (2004) Mol. Biotechnol., 26, pp. 249-261Collins, A.R., Duthie, S.J., Dobson, V.L., Direct enzymic detection of endogenous oxidative base damage in human lymphocyte DNA (1993) Carcinogenesis, 14, pp. 1733-1735Collins, A.R., Olmedilla, B., Southon, S., Granado, F., Duthie, S.J., Serum carotenoids and oxidative DNA damage in human lymphocytes (1998) Carcinogenesis, 19, pp. 2159-2162Davis, C.A., Nick, H.S., Agarwal, A., Manganese superoxide dismutase attenuates cisplatin-induced renal injury: importance of superoxide (2001) J. Am. Soc. Nephrol., 12, pp. 2683-2690Delcourt, C., Korobelnik, J.F., Barberger-Gateau, P., Delyfer, M.N., Rougier, M.B., Le Goff, M., Malet, F., Dartigues, J.F., Nutrition and age-related eye diseases: the alienor (Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes) study (2010) J. Nutr. Health Aging, 14, pp. 854-861Fenech, M., El-Sohemy, A., Cahill, L., Ferguson, L.R., French, T.A., Tai, E.S., Milner, J., Head, R., Nutrigenetics and nutrigenomics: viewpoints on the current status and applications in nutrition research and practice (2011) J. Nutrigenet. Nutrigenomics, 4, pp. 69-89Fletcher, A.E., Free radicals, antioxidants and eye diseases: evidence from epidemiological studies on cataract and age-related macular degeneration (2010) Ophthalmic Res., 44, pp. 191-198Fordel, E., Thijs, L., Moens, L., Dewilde, S., Neuroglobin and cytoglobin expression in mice. Evidence for a correlation with reactive oxygen species scavenging (2007) FEBS J., 274, pp. 1312-1317Gao, X., Dinkova-Kostova, A.T., Talalay, P., Powerful and prolonged protection of human retinal pigment epithelial cells, keratinocytes, and mouse leukemia cells against oxidative damage: the indirect antioxidant effects of sulforaphane (2001) Proc. Natl. Acad. Sci. USA, 98, pp. 15221-15226Gebicki, S., Gebicki, J.M., Crosslinking of DNA and proteins induced by protein hydroperoxides (1999) Biochem. J., 338 (PART 3), pp. 629-636Geuens, E., Brouns, I., Flamez, D., Dewilde, S., Timmermans, J.P., Moens, L., A globin in the nucleus! (2003) J. Biol. Chem., 278, pp. 30417-30420Ghezzi, P., Oxidoreduction of protein thiols in redox regulation (2005) Biochem. Soc. Trans., 33, pp. 1378-1381Hartmann, A., Agurell, E., Beevers, C., Brendler-Schwaab, S., Burlinson, B., Clay, P., Collins, A., Tice, R.R., (2003), 18, pp. 45-51. , Recommendations for conducting the in vivo alkaline Comet assay. In: 4th International Comet Assay Workshop. Mutagenesis volHartree, E.F., Determination of protein: a modification of the Lowry method that gives a linear photometric response (1972) Anal. Biochem., 48, pp. 422-427He, R.R., Tsoi, B., Lan, F., Yao, N., Yao, X.S., Kurihara, H., Antioxidant properties of lutein contribute to the protection against lipopolysaccharide-induced uveitis in mice (2011) Chin. Med., 6, p. 38Kim, J.H., Na, H.J., Kim, C.K., Kim, J.Y., Ha, K.S., Lee, H., Chung, H.T., Kim, Y.M., The non-provitamin A carotenoid, lutein, inhibits NF-kappaB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-kappaB-inducing kinase pathways: role of H(2)O(2) in NF-kappaB activation (2008) Free Radic. Biol. Med., 45, pp. 885-896Klaassen, C.D., Reisman, S.A., Nrf2 the rescue: effects of the antioxidative/electrophilic response on the liver (2010) Toxicol. Appl. Pharmacol., 244, pp. 57-65Leo, M., Santino, D., Tikhonenko, I., Magidson, V., Khodjakov, A., Koonce, M.P., Rules of engagement: centrosome-nuclear connections in a closed mitotic system (2012) Biol. Open, 1, pp. 1111-1117Li, B., Ahmed, F., Bernstein, P.S., Studies on the singlet oxygen scavenging mechanism of human macular pigment (2010) Arch. Biochem. Biophys., 504, pp. 56-60Li, X., Wu, Z., Wang, Y., Mei, Q., Fu, X., Han, W., Characterization of adult alpha- and beta-globin elevated by hydrogen peroxide in cervical cancer cells that play a cytoprotective role against oxidative insults (2013) PLoS ONE, 8, pp. e54342Liebler, D.C., Antioxidant reactions of carotenoids (1993) Ann. N.Y. Acad. Sci., 691, pp. 20-31Lienau, A., Glaser, T., Tang, G., Dolnikowski, G.G., Grusak, M.A., Albert, K., Bioavailability of lutein in humans from intrinsically labeled vegetables determined by LC-APCI-MS (2003) J. Nutr. Biochem., 14, pp. 663-670Liu, W., Baker, S.S., Baker, R.D., Nowak, N.J., Zhu, L., Upregulation of hemoglobin expression by oxidative stress in hepatocytes and its implication in nonalcoholic steatohepatitis (2011) PLoS ONE, 6, pp. e24363Livak, K.J., Schmittgen, T.D., Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method (2001) Methods, 25, pp. 402-408Luxford, C., Dean, R.T., Davies, M.J., Induction of DNA damage by oxidised amino acids and proteins (2002) Biogerontology, 3, pp. 95-102Matsushima, H., Yonemura, K., Ohishi, K., Hishida, A., The role of oxygen free radicals in cisplatin-induced acute renal failure in rats (1998) J. Lab. Clin. Med., 131, pp. 518-526Meister, A., Anderson, M.E., (1983) Annu. Rev. Biochem., 52, pp. 711-760Merk, O., Speit, G., Detection of crosslinks with the comet assay in relationship to genotoxicity and cytotoxicity (1999) Environ. Mol. Mutagen., 33, pp. 167-172Mihara, M., Uchiyama, M., Determination of malonaldehyde precursor in tissues by thiobarbituric acid test (1978) Anal. Biochem., 86, pp. 271-278Miller, R.P., Tadagavadi, R.K., Ramesh, G., Reeves, W.B., Mechanisms of Cisplatin nephrotoxicity (2010) Toxins (Basel), 2, pp. 2490-2518Miyake, S., Kobayashi, S., Tsubota, K., Ozawa, Y., (2014), Phase II enzyme induction by a carotenoid, lutein, in a PC12D neuronal cell line. Biochem. Biophys. Res. CommunNakai, T., Ando, M., Okamoto, Y., Ueda, K., Kojima, N., Modulation of oxidative DNA damage and DNA-crosslink formation induced by cis-diammine-tetrachloro-platinum(IV) in the presence of endogenous reductants (2011) J. Inorg. Biochem., 105, pp. 1-5Newton, D.A., Rao, K.M., Dluhy, R.A., Baatz, J.E., Hemoglobin is expressed by alveolar epithelial cells (2006) J. Biol. Chem., 281, pp. 5668-5676Olfert, E.D., (1993), Guide to the care and use of experimental animals. In: Ernest, D.B.M.C., Olfert, D., DVM, Ann McWilliam, A. (Ed.). Canadian Council on Animal Care, OttawaPark, J.S., Chew, B.P., Wong, T.S., Zhang, J.X., Magnuson, N.S., Dietary lutein but not astaxanthin or beta-carotene increases pim-1 gene expression in murine lymphocytes (1999) Nutr. Cancer, 33, pp. 206-212Peres, L.A., da Cunha, A.D., Acute nephrotoxicity of cisplatin: molecular mechanisms (2013) J. Bras. Nefrol., 35, pp. 332-340Pfuhler, S., Wolf, H.U., Detection of DNA-crosslinking agents with the alkaline comet assay (1996) Environ. Mol. Mutagen., 27, pp. 196-201Rafi, M.M., Shafaie, Y., Dietary lutein modulates inducible nitric oxide synthase (iNOS) gene and protein expression in mouse macrophage cells (RAW 264.7) (2007) Mol. Nutr. Food Res., 51, pp. 333-340Santocono, M., Zurria, M., Berrettini, M., Fedeli, D., Falcioni, G., Influence of astaxanthin, zeaxanthin and lutein on DNA damage and repair in UVA-irradiated cells (2006) J. Photochem. Photobiol., B, 85, pp. 205-215Sedlak, J., Lindsay, R.H., Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent (1968) Anal. Biochem., 25, pp. 192-205Serpeloni, J.M., Grotto, D., Mercadante, A.Z., de Lourdes Pires Bianchi, M., Antunes, L.M., Lutein improves antioxidant defense in vivo and protects against DNA damage and chromosome instability induced by cisplatin (2010) Arch. Toxicol., 84, pp. 811-822Serpeloni, J.M., Barcelos, G.R., Friedmann Angeli, J.P., Mercadante, A.Z., Lourdes Pires Bianchi, M., Antunes, L.M., Dietary carotenoid lutein protects against DNA damage and alterations of the redox status induced by cisplatin in human derived HepG2 cells (2012) Toxicol. In Vitro, 26, pp. 288-294Sindhu, E.R., Preethi, K.C., Kuttan, R., Antioxidant activity of carotenoid lutein in vitro and in vivo (2010) Indian J. Exp. Biol., 48, pp. 843-848Singh, N.P., McCoy, M.T., Tice, R.R., Schneider, E.L., A simple technique for quantitation of low levels of DNA damage in individual cells (1988) Exp. Cell Res., 175, pp. 184-191Speit, G., Hartmann, A., The comet assay: a sensitive genotoxicity test for the detection of DNA damage (2005) Methods Mol. Biol., 291, pp. 85-95Stahl, W., Sies, H., (2011), Photoprotection by dietary carotenoids: concept, mechanisms, evidence and future development. Mol. Nutr. Food ResSugiyama, S., Hayakawa, M., Kato, T., Hanaki, Y., Shimizu, K., Ozawa, T., Adverse effects of anti-tumor drug, cisplatin, on rat kidney mitochondria: disturbances in glutathione peroxidase activity (1989) Biochem. Biophys. Res. Commun., 159, pp. 1121-1127Tice, R.R., Agurell, E., Anderson, D., Burlinson, B., Hartmann, A., Kobayashi, H., Miyamae, Y., Sasaki, Y.F., Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing (2000) Environ. Mol. Mutagen., 35, pp. 206-221Tikhonenko, I., Magidson, V., Graf, R., Khodjakov, A., Koonce, M.P., A kinesin-mediated mechanism that couples centrosomes to nuclei (2013) Cell. Mol. Life Sci., 70, pp. 1285-1296Tiso, M., Tejero, J., Basu, S., Azarov, I., Wang, X., Simplaceanu, V., Frizzell, S., Gladwin, M.T., Human neuroglobin functions as a redox-regulated nitrite reductase (2011) J. Biol. Chem., 286, pp. 18277-18289Trujillo, E., Davis, C., Milner, J., Nutrigenomics, proteomics, metabolomics, and the practice of dietetics (2006) J. Am. Diet. Assoc., 106, pp. 403-413Wang, D., Lippard, S.J., Cellular processing of platinum anticancer drugs (2005) Nat. Rev. Drug. Discov., 4, pp. 307-320Wang, M., Tsao, R., Zhang, S., Dong, Z., Yang, R., Gong, J., Pei, Y., Antioxidant activity, mutagenicity/anti-mutagenicity, and clastogenicity/anti-clastogenicity of lutein from marigold flowers (2006) Food Chem. Toxicol., 44, pp. 1522-1529Waye, J.S., Eng, B., Diagnostic testing for alpha-globin gene disorders in a heterogeneous North American population (2013) Int. J. Lab. Hematol., 35, pp. 306-313Wozniak, K., Blasiak, J., Recognition and repair of DNA-cisplatin adducts (2002) Acta Biochim. Pol., 49, pp. 583-596Zhang, Z., Han, S., Wang, H., Wang, T., Lutein extends the lifespan of Drosophila melanogaster (2014) Arch. Gerontol. Geriatr., 58, pp. 153-15
In Vivo Assessment Of The Cytotoxic, Genotoxic And Antigenotoxic Potential Of Maná-cubiu (solanum Sessiliflorum Dunal) Fruit
Solanum sessiliflorum Dunal is a native shrub often found in the Amazon Forest. Its fruits, known as maná-cubiu, possess an unusual flavor and are consumed in salads and juices, mainly by the local community of Northern Brazil. Because these fruits are used in traditional medicine as hypoglycemic and hypocholesterolemic agents, it is important to establish whether the consumption of maná-cubiu is safe using in vivo genotoxicity tests. Here, we investigated the genotoxic and antigenotoxic potential of maná-cubiu for doxorubicin (DXR)-induced DNA damage using the micronucleus test and the comet assay in Wistar rats. Moreover, oxidative stress parameters were determined in the heart and liver of the animals by measuring the thiobarbituric acid reactive substances (TBARS), a biomarker of lipid peroxidation, and reduced glutathione (GSH) content. The relative expression of Ptgs2 mRNA in the livers of the animals was also determined. The tests were performed with maná-cubiu pulp (125, 250, 375 or 500. mg/kg body weight - b.w.) by gavage for 14. days, followed by intraperitoneal injection of saline or DXR (16. mg/kg b.w.) immediately after the last gavage, which occurred 24. h before euthanasia. The results showed that maná-cubiu at all tested doses had no cytotoxic effects on bone marrow cells and was not genotoxic to heart or liver cells. In addition, maná-cubiu treatments decreased DXR-induced DNA damage according to the comet assay in heart and liver cells. Reductions in micronucleus frequency in peripheral blood cells occurred at 125, 250 and 375. mg/kg b.w. doses of maná-cubiu, and the TBARS content induced by DXR was also reduced by maná-cubiu. Furthermore, maná-cubiu did not modulate the transcription of the Ptgs2 gene. In conclusion, maná-cubiu pulp fruit was not cytotoxic or genotoxic in Wistar rats, suggesting its safety for human consumption, at least considering genotoxic effects. The antioxidant capacity of maná-cubiu pulp fruit may contribute to the antigenotoxic effects of this fruit at the doses used in this study. © 2014 Elsevier Ltd.62121127Aissa, A.F., Bianchi, M.L.P., Ribeiro, J.C., Hernandes, L.C., de Faria, A.F., Mercadante, A.Z., Comparative study of beta-carotene and microencapsulated beta-carotene: Evaluation of their genotoxic and antigenotoxic effects (2012) Food and Chemical Toxicology, 50 (5), pp. 1418-1424Almeida, M.R., Aissa, A.F., Gomes, T.D.U.H., Darin, J.D.C., Chiste, R.C., Mercadante, A.Z., In vivo genotoxicity and oxidative stress evaluation of an ethanolic extract from piquia (Caryocar villosum) pulp (2013) Journal of Medicinal Food, 16 (3), pp. 268-271Boeing, H., Bechthold, A., Bub, A., Ellinger, S., Haller, D., Kroke, A., Critical review: Vegetables and fruit in the prevention of chronic diseases (2012) European Journal of Nutrition, 51 (6), pp. 637-663Bowen, D.E., Whitwell, J.H., Lillford, L., Henderson, D., Kidd, D., Mc Garry, S., Evaluation of a multi-endpoint assay in rats, combining the bone-marrow micronucleus test, the Comet assay and the flow-cytometric peripheral blood micronucleus test (2011) Mutation Research, 722 (1), pp. 7-19Buege, J.A., Aust, S.D., Microsomal lipid peroxidation (1978) Methods in Enzymology, 52, pp. 302-310Carvalho, C., Santos, R.X., Cardoso, S., Correia, S., Oliveira, P.J., Santos, M.S., Doxorubicin: The good, the bad and the ugly effect (2009) Current Medicinal Chemistry, 16 (25), pp. 3267-3285Chang, C.V., Felicio, A.C., Reis, J.E., Guerra Mde, O., Peters, V.M., Fetal toxicity of Solanum lycocarpum (Solanaceae) in rats (2002) Journal of Ethnopharmacology, 81 (2), pp. 265-269de Angelis Pereira, M.C., Carvalho, J.C., Lima, L.M., Caputo, L.R., Ferreira, L.R., Fiorini, J.E., Toxicity of a subchronic treatment with hydroalcoholic crude extract from Solanum grandiflorum (Ruiz et Pav) in rats (2003) Journal of Ethnopharmacology, 89 (1), pp. 97-99Doroshow, J.H., Davies, K.J.A., Redox cycling of anthracyclines by cardiac mitochondria. 2. Formation of superoxide anion, hydrogen-peroxide, and hydroxyl radical (1986) Journal of Biological Chemistry, 261 (7), pp. 3068-3074Fang, Y.Z., Yang, S., Wu, G., Free radicals, antioxidants, and nutrition (2002) Nutrition, 18 (10), pp. 872-879Felzenszwalb, I., da Costa Marques, M.R., Mazzei, J.L., Aiub, C.A., Toxicological evaluation of Euterpe edulis: A potential superfruit to be considered (2013) Food and Chemical Toxicology, 58, pp. 536-544Fenech, M., Micronutrients and genomic stability: A new paradigm for recommended dietary allowances (RDAs) (2002) Food and Chemical Toxicology, 40 (8), pp. 1113-1117Fraga, C.G., Relevance, essentiality and toxicity of trace elements in human health (2005) Molecular Aspects of Medicine, 26 (4-5), pp. 235-244Gilleron, M., Marechal, X., Montaigne, D., Franczak, J., Neviere, R., Lancel, S., NADPH oxidases participate to doxorubicin-induced cardiac myocyte apoptosis (2009) Biochemical and Biophysical Research Communications, 388 (4), pp. 727-731Granados-Principal, S., Quiles, J.L., Ramirez-Tortosa, C.L., Sanchez-Rovira, P., Ramirez-Tortosa, M.C., New advances in molecular mechanisms and the prevention of adriamycin toxicity by antioxidant nutrients (2010) Food and Chemical Toxicology, 48 (6), pp. 1425-1438Hartree, E.F., Determination of protein: A modification of the Lowry method that gives a linear photometric response (1972) Analytical Biochemistry, 48 (2), pp. 422-427Hayashi, M., Morita, T., Kodama, Y., Sofuni, T., Ishidate, M., The micronucleus assay with mouse peripheral-blood reticulocytes using acridine orange-coated slides (1990) Mutation Research, 245 (4), pp. 245-249Holden, H.E., Majeska, J.B., Studwell, D., A direct comparison of mouse and rat bone marrow and blood as target tissues in the micronucleus assay (1997) Mutation Research-Genetic Toxicology and Environmental Mutagenesis, 391 (1-2), pp. 87-89Johanningsmeier, S.D., Harris, G.K., Pomegranate as a functional food and nutraceutical source (2011) Annual Review of Food Science and Technology, 2 (2), pp. 181-201Kumar, M., Kumar, S., Kaur, S., Role of ROS and COX-2/iNOS inhibition in cancer chemoprevention: A review (2012) Phytochemistry Reviews, 11 (2-3), pp. 309-337Liu, R.H., Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals (2003) The American Journal of Clinical Nutrition, 78 (3 SUPPL.), pp. 517S-520SLiu, R.H., Dietary bioactive compounds and their health implications (2013) Journal of Food Science, 78, pp. A18-A25Macgregor, J.T., Heddle, J.A., Hite, M., Margolin, B.H., Ramel, C., Salamone, M.F., Guidelines for the conduct of micronucleus assays in mammalian bone-marrow erythrocytes (1987) Mutation Research, 189 (2), pp. 103-112Marin, A.M.F., Siqueira, E.M.A., Arruda, S.F., Minerals, phytic acid and tannin contents of 18 fruits from the Brazilian savanna (2009) International Journal of Food Sciences and Nutrition, 60, pp. 177-187Marx, F., Andrade, E.H.A., Maia, J.G., Chemical composition of the fruit of Solanum sessiliflorum (1998) Zeitschrift für Lebensmittel-Untersuchung und -Forschung, 206 (5), pp. 364-366Nardi, E.P., Evangelista, F.S., Tormen, L., SaintPierre, T.D., Curtius, A.J., de Souza, S.S., The use of inductively coupled plasma mass spectrometry (ICP-MS) for the determination of toxic and essential elements in different types of food samples (2009) Food Chemistry, 112 (3), pp. 727-732Pardo, M.A., Efecto de Solanum sessilif lorum Dunal sobre el metabolismo lipidico y de la glucosa (2004) Ciencia e Investigación, 7, pp. 43-48Pfaffl, M.W., A new mathematical model for relative quantification in real-time RT-PCR (2001) Nucleic Acids Research, 29 (9)Rietjens, I.M.C.M., Slob, W., Galli, C., Silano, V., Risk assessment of botanicals and botanical preparations intended for use in food and food supplements: Emerging issues (2008) Toxicology Letters, 180 (2), pp. 131-136Rigano, M.M., De Guzman, G., Walmsley, A.M., Frusciante, L., Barone, A., Production of pharmaceutical proteins in Solanaceae food crops (2013) International Journal of Molecular Sciences, 14 (2), pp. 2753-2773Rodrigues, E., Mariutti, L.R., Mercadante, A.Z., Carotenoids and phenolic compounds from Solanum sessiliflorum, an unexploited Amazonian fruit, and their scavenging capacities against reactive oxygen and nitrogen species (2013) Journal of Agricultural and Food Chemistry, 61 (12), pp. 3022-3029Rothfuss, A., Honma, M., Czich, A., Aardema, M.J., Burlinson, B., Galloway, S., Improvement of in vivo genotoxicity assessment: Combination of acute tests and integration into standard toxicity testing (2011) Mutation Research, 723 (2), pp. 108-120Salick, J., Cocona (Solanum sessiliflorum) production and breeding potentials of the peach tomato (1989) New crops for food and industry, pp. 257-264. , Chapman and Hall, London, G.E. Wickens, N. Haq, P. Day (Eds.)Sanchez-Lamar, A., Fonseca, G., Fuentes, J.L., Cozzi, R., Cundari, E., Fiore, M., Assessment of the genotoxic risk of Punica granatum L. (Punicaceae) whole fruit extracts (2008) Journal of Ethnopharmacology, 115 (3), pp. 416-422Sedlak, J., Lindsay, R.H., Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent (1968) Analytical Biochemistry, 25 (1), pp. 192-205Simunek, T., Sterba, M., Popelova, O., Adamcova, M., Hrdina, R., Gersl, V., Anthracycline-induced cardiotoxicity: Overview of studies examining the roles of oxidative stress and free cellular iron (2009) Pharmacological Reports, 61 (1), pp. 154-171Singh, N.P., Mccoy, M.T., Tice, R.R., Schneider, E.L., A simple technique for quantitation of low-levels of DNA damage in individual cells (1988) Experimental Cell Research, 175 (1), pp. 184-191Tavares, D.C., Munari, C.C., Araujo, M.G., Beltrame, M.C., Furtado, M.A., Goncalves, C.C., Antimutagenic potential of Solanum lycocarpum against induction of chromosomal aberrations in V79 cells and micronuclei in mice by doxorubicin (2011) Planta Medica, 77 (13), pp. 1489-1494Tice, R.R., Agurell, E., Anderson, D., Burlinson, B., Hartmann, A., Kobayashi, H., Single cell gel/comet assay: Guidelines for in vitro and in vivo genetic toxicology testing (2000) Environmental and Molecular Mutagenesis, 35 (3), pp. 206-221Udani, J.K., Singh, B.B., Singh, V.J., Barrett, M.L., Effects of Acai (Euterpe oleracea Mart.) berry preparation on metabolic parameters in a healthy overweight population: A pilot study (2011) Nutrition Journal, 10, p. 45Vieira, P.M., Santos, S.C., Chen-Chen, L., Assessment of mutagenicity and cytotoxicity of Solanum paniculatum L. extracts using in vivo micronucleus test in mice (2010) Brazilian Journal of Biology, 70 (3), pp. 601-606Waters, M.D., Brady, A.L., Stack, H.F., Brockman, H.E., Antimutagenicity profiles for some model compounds (1990) Mutation Research, 238 (1), pp. 57-85Williams, C.S., Mann, M., DuBois, R.N., The role of cyclooxygenases in inflammation, cancer, and development (1999) Oncogene, 18 (55), pp. 7908-7916Wolfsegger, M.J., Jaki, T., Dietrich, B., Kunzler, J.A., Barker, K., A note on statistical analysis of organ weights in non-clinical toxicological studies (2009) Toxicology and Applied Pharmacology, 240 (1), pp. 117-12