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.62 121127Aissa, 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. 117-122