title: Anthracycline-induced cardiac toxicity is not increased by dietary omega-3 fatty acids.
abstract: Exogenous n-3 polyunsaturated fatty acids (PUFA) and specially docosahexaenoic acid (DHA) have been previously reported to potentiate the efficacy of anticancer agents that generate an oxidative stress, such as anthracyclines, by enhancing the susceptibility of cell membranes to lipid peroxidation. Since lipid peroxidation has also been suggested to mediate anthracycline-induced heart failure, we designed a study aimed at investigating whether a DHA-enriched diet coupled with controlled oxidative conditions prevents or aggravates this serious side effect in vivo. Female Sprague-Dawley rats were submitted for at least 3 weeks to diet enriched in DHA, which was provided either as natural oil (sardine oil, experiment 1) or in a purified form (DHASCO, experiment 2). At the same time, to constrain the nutritional oxidative status, the anti-oxidant Vitamin E or the pro-oxidant menadione/sodium ascorbate redox mixture was added. Then, epirubicin was administered weekly at two cumulative doses, 9 mg x kg(-1) (experiment 1) or 15 mg x kg(-1) (experiment 2). Cardiotoxicity was assessed by electrocardiographic (ECG) and hemodynamic measurements, completed with histological examination. Epirubicin-induced dose-dependent mortality, alterations of hemodynamic parameters and histological damages, all features characterizing the occurrence of congestive heart failure. Moreover, the addition of anti- or pro-oxidant did not change the hemodynamics either at the lowest (experiment 1) or the highest dose (experiment 2). Similarly, the ECG measurements and histological examinations did not reveal any difference. DHA was actually incorporated, as evaluated through the adipose tissue fatty acid composition. All these observations indicated that the DHA-enriched diet, placed under controlled oxidative conditions, did not appear to prevent but neither to aggravate epirubicin-induced cardiotoxicity. These findings support the idea that DHA improves the anthracycline therapeutic index.
authors.affiliation: Nutrition, Croissance et Cancer, INSERM EMI-U 0211, Université François-Rabelais, CORAD, CHU Bretonneau, F-37044, Tours, France.
authors.forename: E
authors.initials: E
authors.lastname: Germain
authors.forename: P
authors.initials: P
authors.lastname: Bonnet
authors.forename: L
authors.initials: L
authors.lastname: Aubourg
authors.forename: M C
authors.initials: MC
authors.lastname: Grangeponte
authors.forename: V
authors.initials: V
authors.lastname: Chajès
authors.forename: P
authors.initials: P
authors.lastname: Bougnoux
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D004032:Diet; D004562:Electrocardiography / Q000187:drug effects; D015251:Epirubicin / Q000009:adverse effects*; D005227:Fatty Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology*; D006334:Heart Function Tests; D009206:Myocardium / Q000473:pathology; D010084:Oxidation-Reduction; D051381:Rats
chemical_list: D000903:Antibiotics, Antineoplastic; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D015251:Epirubicin