title: Hydroxytyrosol ameliorates oxidative stress and mitochondrial dysfunction in doxorubicin-induced cardiotoxicity in rats with breast cancer.
abstract: Oxidative stress is involved in several processes including cancer, aging and cardiovascular disease, and has been shown to potentiate the therapeutic effect of drugs such as doxorubicin. Doxorubicin causes significant cardiotoxicity characterized by marked increases in oxidative stress and mitochondrial dysfunction. Herein, we investigate whether doxorubicin-associated chronic cardiac toxicity can be ameliorated with the antioxidant hydroxytyrosol in rats with breast cancer. Thirty-six rats bearing breast tumors induced chemically were divided into 4 groups: control, hydroxytyrosol (0.5mg/kg, 5days/week), doxorubicin (1mg/kg/week), and doxorubicin plus hydroxytyrosol. Cardiac disturbances at the cellular and mitochondrial level, mitochondrial electron transport chain complexes I-IV and apoptosis-inducing factor, and oxidative stress markers have been analyzed. Hydroxytyrosol improved the cardiac disturbances enhanced by doxorubicin by significantly reducing the percentage of altered mitochondria and oxidative damage. These results suggest that hydroxytyrosol improve the mitochondrial electron transport chain. This study demonstrates that hydroxytyrosol protect rat heart damage provoked by doxorubicin decreasing oxidative damage and mitochondrial alterations.
authors.affiliation: Department of Biochemistry and Molecular Biology II, Biomedical Research Center, Granada, Spain; "José Mataix" Institute of Nutrition and Food Technology, Biomedical Research Center, Granada, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Granados-Principal
authors.affiliation: Department of Biochemistry and Molecular Biology II, Biomedical Research Center, Granada, Spain; "José Mataix" Institute of Nutrition and Food Technology, Biomedical Research Center, Granada, Spain.
authors.forename: Nuri
authors.initials: N
authors.lastname: El-Azem
authors.affiliation: Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRB, Lleida, Spain.
authors.forename: Reinald
authors.initials: R
authors.lastname: Pamplona
authors.affiliation: Pathological Anatomy Service, Jaen City Hospital, Jaen, Spain.
authors.forename: Cesar
authors.initials: C
authors.lastname: Ramirez-Tortosa
authors.affiliation: Department of Biochemistry and Molecular Biology II, Biomedical Research Center, Granada, Spain; "José Mataix" Institute of Nutrition and Food Technology, Biomedical Research Center, Granada, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Pulido-Moran
authors.affiliation: GENYO, Granada, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Vera-Ramirez
authors.affiliation: "José Mataix" Institute of Nutrition and Food Technology, Biomedical Research Center, Granada, Spain; Department of Physiology, Biomedical Research Center, Granada, Spain.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Quiles
authors.affiliation: Oncology Service, Jaen City Hospital, Jaen, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Sanchez-Rovira
authors.affiliation: Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRB, Lleida, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Naudí
authors.affiliation: Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRB, Lleida, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Portero-Otin
authors.affiliation: "José Mataix" Institute of Nutrition and Food Technology, Biomedical Research Center, Granada, Spain; Department of Physiology, Biomedical Research Center, Granada, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Perez-Lopez
authors.affiliation: Department of Biochemistry and Molecular Biology II, Biomedical Research Center, Granada, Spain; "José Mataix" Institute of Nutrition and Food Technology, Biomedical Research Center, Granada, Spain. Electronic address: mramirez@ugr.es.
authors.forename: Mcarmen
authors.initials: M
authors.lastname: Ramirez-Tortosa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D004317:Doxorubicin; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006331:Heart Diseases / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D015151:Immunoblotting; D015674:Mammary Neoplasms, Animal / Q000150:complications / Q000378:metabolism*; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D051033:Apoptosis Inducing Factor; D005227:Fatty Acids; C005975:3,4-dihydroxyphenylethanol; D004317:Doxorubicin; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D010626:Phenylethyl Alcohol
keywords: Apoptosis-inducing factor; Chemo toxicity; Electron transport chain; Hydroxytyrosol; Oxidative stress; Protein damage