Nutrition Modulation of Cardiotoxicity and Anticancer Efficacy Related to Doxorubicin Chemotherapy by Glutamine and omega-3 Polyunsaturated Fatty Acids

卷:40

Xue, Hongyu ; Ren, Wenhua ; Denkinger, Melanie ; Schlotzer, Ewald ; Wischmeyer, Paul E.

Univ Colorado Denver

关键词: fatty acids;    research and diseases;    amino acids;    oncology;    breast cancer;    glutamine;    doxorubicin;    cardiotoxicity;   

DOI  :  10.1177/0148607115581838

学科分类：食品科学和技术

【 摘 要 】

Background: Doxorubicin (DOX) has been one of the most effective antitumor agents against a broad spectrum of malignancies. However, DOX-induced cardiotoxicity forms the major cumulative dose-limiting factor. Glutamine and -3 polyunsaturated fatty acids (PUFAs) are putatively cardioprotective during various stresses and/or have potential chemosensitizing effects during cancer chemotherapy. Methods: Antitumor activity and cardiotoxicity of DOX treatment were evaluated simultaneously in a MatBIII mammary adenocarcinoma tumor-bearing rat model treated with DOX (cumulative dose 12 mg/kg). Single or combined treatment of parenteral glutamine (0.35 g/kg) and -3 PUFAs (0.19 g/kg eicosapentaenoic acid and 0.18 g/kg docosahexaenoic acid) was administered every other day, starting 6 days before chemotherapy initiation until the end of study (day 50). Results: Glutamine alone significantly prevented DOX-related deterioration of cardiac function, reduced serum cardiac troponin I levels, and diminished cardiac lipid peroxidation while not affecting tumor inhibition kinetics. Single -3 PUFA treatment significantly enhanced antitumor activity of DOX associated with intensified tumoral oxidative stress and enhanced tumoral DOX concentration while not potentiating cardiac dysfunction or increasing cardiac oxidative stress. Intriguingly, providing glutamine and -3 PUFAs together did not consistently confer a greater benefit; conversely, individual benefits on cardiotoxicity and chemosensitization were mostly attenuated or completely lost when combined. Conclusions: Our data demonstrate an interesting differentiality or even dichotomy in the response of tumor and host to single parenteral glutamine and -3 PUFA treatments. The intriguing glutamine x -3 PUFA interaction observed draws into question the common assumption that there are additive benefits of combinations of nutrients that are beneficial on an individual basis.