Oil rich in carotenoids instead of vitamins C and E as a better option to reduce doxorubicin-induced damage to normal cells of Ehrlich tumor-bearing mice: hematological, toxicological and histopathological evaluations☆ Ana Luisa Miranda-Vilela a,b, ⁎ , Cesar K. Grisolia a , João Paulo F. Longo a , Raphael C.A. Peixoto c , Marcos Célio de Almeida a , Lilian Carla P. Barbosa c , Mariana M. Roll a , Flávia A. Portilho a , Luciana L.C. Estevanato a , Anamélia L. Bocca c , Sônia N. Báo c , Zulmira G.M. Lacava a, ⁎ a Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasilia, Brazil b Faculty of Medicine, Faciplac, Campus Gama/DF, Brazil c Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasília, Brazil Received 14 January 2014; received in revised form 5 June 2014; accepted 6 June 2014 Abstract The development of therapeutic strategies to attenuate chemotherapy toxicity represents an area of great interest in cancer research, and among them is nutritional therapy based on antioxidants. As research on this topic is still controversial and scarce, we aim to investigate the effects of antioxidant supplementation with vitamin C, vitamin E or pequi oil, a carotenoid-rich oil extracted from pequi (Caryocar brasiliense), on doxorubicin (DX)-induced oxidative damage to normal cells in Ehrlich solid tumor-bearing mice. Tumor weight and volume, histopathology, morphometry and immunohistochemistry were used to assess the treatments' efficacy in containing tumor aggressiveness and regression, while possible toxicity of treatments was assessed by animals' weight, morphological analysis of the heart, liver and kidneys, hemogram, and serum levels of total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, creatinine and urea. Although all the chemotherapeutic treatments increased internal necrosis area and reduced the positive Ki-67 cells compared to non-treated tumors, the treatments with pequi oil provided before tumor inoculation (PTDX) or in continuous and concurrent administration with doxorubicin (PTPDX) were more effective in containing tumor growth, besides increasing lymphocyte-dependent immunity and reducing the adverse side effects associated with DX-induced oxidative damage to normal cells, mainly the PTDX treatment. Vitamins C and E given before tumor inoculation and chemotherapy were not successful against doxorubicin-induced cardiotoxicity, besides increasing doxorubicin-induced nephrotoxicity, indicating that, at least for doxorubicin, pequi oil instead of vitamins C and E would be the best option to reduce its adverse effects. © 2014 Elsevier Inc. All rights reserved. Keywords: Doxorubicin-induced damage; Pequi oil (Caryocar brasiliense); Chemotherapy; Breast cancer; Animal model 1. Introduction Breast cancer is the second most common type of cancer in the world and the most common among women both in the developed and the developing world. It accounts globally for 23% of all cancers in women and 14% of cancer deaths, being the commonest cause of death for cancer in women worldwide [1–5]. Although the emergence and evolution of new therapeutic approaches such as chemotherapy, radiotherapy, hormonal therapy, immunotherapy and conservative surgery have occurred in the last half century [6,7], breast cancer Available online at www.sciencedirect.com ScienceDirect Journal of Nutritional Biochemistry xx (2014) xxx – xxx Abbreviations: DX, doxorubicin; ROS, reactive oxygen species; RBC, red blood cells; HGB, hemoglobin; HCT, hematocrit; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; RDW, red cell distribution width; WBC, total white blood cells; PLT, platelet count; MPV, mean platelet volume; P-LCR, platelet large cell ratio; PDW, platelet distribution width; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma glutamyl transferase; MN-NCE, micronucleus frequency for normochromatic erythrocytes; MN-PCE, micronucleus frequency for polychromatic erythrocytes; %PCE, frequency of polychromatic erythrocytes. ☆ Funding sources: The Brazilian National Council for Technological and Scientific Development (CNPq), the Foundation to Support Research in the Federal District (FAPDF), the Coordination for Further Training of Graduate Staff (CAPES), the CAPES-Network CON-NANO (CAPES), the INCT-Nanobiotecnologia (MCT, CNPq, CAPES), CNANO-UnB, and DPP-UnB. ⁎ Corresponding author. Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasilia, Brazil. Tel.: +55 61 3107 3087; fax: +55 61 3107 2923. E-mail addresses: mirandavilela@unb.br (A.L. Miranda-Vilela), zulmira@unb.br (Z.G.M. Lacava). http://dx.doi.org/10.1016/j.jnutbio.2014.06.005 0955-2863/© 2014 Elsevier Inc. All rights reserved.