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Nutritional modulation of cardiotoxicity and anti‐cancer efficacy related to doxorubicin chemotherapy by glutamine and n‐3 PUFAs (123.8)
Author(s) -
Xue Hongyu,
Ren Wenhua,
Wischmeyer Paul
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.123.8
Subject(s) - cardiotoxicity , glutamine , doxorubicin , pharmacology , polyunsaturated fatty acid , medicine , chemotherapy , cancer , biochemistry , chemistry , fatty acid , amino acid
Doxorubicin (DOX) has been one of the most effective antitumor agents against a broad spectrum of malignancies. However, DOX‐induced cardiotoxicity forms the major factor limiting the dose escalation of the drug. We here comparatively examined how glutamine and n‐3 PUFAs, when provided individually and in combination, would affect cardiotoxicity and anti‐tumor efficacy related to DOX (cumulative dose 12mg/kg) in a female Fisher rat model bearing mammary adenocarcinoma. Both single glutamine (0.5 g/kg/d) and n‐3 PUFA (EPA+DHA, 0.4g/kg/d) treatments prevented cardiac function deterioration, reducd serum cardiac troponin I levels, attenuated lipid peroxidation and preserved anti‐oxidant enzymatic reserve in the cardiac tissue. Single n‐3 PUFA treatment significantly enhanced anti‐tumor activity of DOX. Intriguingly, providing glutamine and n‐3 PUFAs together did not confer a greater benefit; conversely, individual benefits on cardiotoxicity and anti‐tumor efficacy associated with single treatments were instead partially or completely lost when the nutrients were combined. Both glutamine and n‐3 PUFA have the potential to be developed as novel individual adjuncts for DOX‐based chemotherapy, but may antagonize each other’s effects when combined. This work draws into question the common assumption that there are additive benefits of combinations of nutrients, which are beneficial on an individual basis. Grant Funding Source : American Society of Parenteral and Enteral Nutrition