Abstract
This study investigated the combined effects of trans fat diet (TFD) and doxorubicin upon cardiac oxidative, inflammatory, and coagulatory stress. TFD increased trans fatty acid deposit in heart (P < 0.05), and decreased protein C and antithrombin-III activities in circulation (P < 0.05). TFD plus doxorubicin treatment elevated activities of plasminogen activator inhibitor-1, lactate dehydrogenase, and creatine phosphokinase (P < 0.05). This combination also raised xanthine oxidase activity, and enhanced cardiac levels of reactive oxygen species, interleukin (IL)-6, IL-10, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 than TFD or doxorubicin treatment alone (P < 0.05). TFD alone increased cardiac nuclear factor kappa B (NF-κB) activity (P < 0.05), but failed to affect expression of NF-κB and mitogen-activated protein kinase (MAPK) (P > 0.05). Doxorubicin treatment alone augmented cardiac activity, mRNA expression, and protein production of NF-κB and MAPK (P < 0.05). TFD plus doxorubicin treatment further upregulated cardiac expression of NF-κB p65, p-p38, and p-ERK1/2 (P < 0.05). These findings suggest that TFD exacerbates doxorubicin-induced cardiotoxicity.
Keywords:
MAPK; NF-κB; cardiac injury; coagulation; doxorubicin; trans fat.
© 2013 Institute of Food Technologists®
MeSH terms
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Animals
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Antithrombin III / antagonists & inhibitors
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Antithrombin III / metabolism
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C-Reactive Protein / metabolism
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Cardiotoxins / toxicity*
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Chemokine CCL2 / metabolism
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Creatine Kinase / blood
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Dietary Fats / adverse effects*
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Doxorubicin / toxicity*
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Fibrinogen / metabolism
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Heart Diseases / chemically induced
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Heart Diseases / pathology
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Interleukin-10 / metabolism
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Interleukin-6 / metabolism
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L-Lactate Dehydrogenase / blood
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Male
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Mice
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Mice, Inbred C57BL
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Mitogen-Activated Protein Kinases / metabolism
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Plasminogen Activator Inhibitor 1 / agonists
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Plasminogen Activator Inhibitor 1 / blood
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Protein C / antagonists & inhibitors
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Protein C / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reactive Oxygen Species / blood
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Trans Fatty Acids / adverse effects*
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Transcription Factor RelA / genetics
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Transcription Factor RelA / metabolism
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Triglycerides / blood
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Tumor Necrosis Factor-alpha / metabolism
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Up-Regulation
Substances
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Cardiotoxins
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Ccl2 protein, mouse
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Chemokine CCL2
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Dietary Fats
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Interleukin-6
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NF-kappa B
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Plasminogen Activator Inhibitor 1
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Protein C
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RNA, Messenger
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Reactive Oxygen Species
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Trans Fatty Acids
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Transcription Factor RelA
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Triglycerides
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Tumor Necrosis Factor-alpha
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Interleukin-10
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Doxorubicin
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Antithrombin III
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Fibrinogen
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C-Reactive Protein
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L-Lactate Dehydrogenase
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Mitogen-Activated Protein Kinases
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Creatine Kinase