title: 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.
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.
authors.affiliation: Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasilia, Brazil; Faculty of Medicine, Faciplac, Campus Gama/DF, Brazil. Electronic address: mirandavilela@unb.br.
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: Miranda-Vilela
authors.affiliation: Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasilia, Brazil.
authors.forename: Cesar K
authors.initials: CK
authors.lastname: Grisolia
authors.affiliation: Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasilia, Brazil.
authors.forename: João Paulo F
authors.initials: JPF
authors.lastname: Longo
authors.affiliation: Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasília, Brazil.
authors.forename: Raphael C A
authors.initials: RCA
authors.lastname: Peixoto
authors.affiliation: Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasilia, Brazil.
authors.forename: Marcos Célio
authors.initials: MC
authors.lastname: de Almeida
authors.affiliation: Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasília, Brazil.
authors.forename: Lilian Carla P
authors.initials: LCP
authors.lastname: Barbosa
authors.affiliation: Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasilia, Brazil.
authors.forename: Mariana M
authors.initials: MM
authors.lastname: Roll
authors.affiliation: Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasilia, Brazil.
authors.forename: Flávia A
authors.initials: FA
authors.lastname: Portilho
authors.affiliation: Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasilia, Brazil.
authors.forename: Luciana L C
authors.initials: LLC
authors.lastname: Estevanato
authors.affiliation: Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasília, Brazil.
authors.forename: Anamélia L
authors.initials: AL
authors.lastname: Bocca
authors.affiliation: Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasília, Brazil.
authors.forename: Sônia N
authors.initials: SN
authors.lastname: Báo
authors.affiliation: Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasilia, Brazil. Electronic address: zulmira@unb.br.
authors.forename: Zulmira G M
authors.initials: ZGM
authors.lastname: Lacava
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use / Q000633:toxicity*; D001205:Ascorbic Acid / Q000032:analysis; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002338:Carotenoids / Q000032:analysis*; D004317:Doxorubicin / Q000627:therapeutic use / Q000633:toxicity*; D005260:Female; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010938:Plant Oils / Q000737:chemistry* / Q000494:pharmacology; D014810:Vitamin E / Q000032:analysis
chemical_list: D000903:Antibiotics, Antineoplastic; D010938:Plant Oils; D014810:Vitamin E; D002338:Carotenoids; D004317:Doxorubicin; D001205:Ascorbic Acid
keywords: Animal model; Breast cancer; Chemotherapy; Doxorubicin-induced damage; Pequi oil (Caryocar brasiliense)