Dietary trans fats enhance doxorubicin-induced cardiotoxicity in mice

J Food Sci. 2013 Oct;78(10):H1621-H1628. doi: 10.1111/1750-3841.12257. Epub 2013 Sep 11.

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.

MeSH terms

  • Animals
  • Antithrombin III / antagonists & inhibitors
  • Antithrombin III / metabolism
  • C-Reactive Protein / metabolism
  • Cardiotoxins / toxicity*
  • Chemokine CCL2 / metabolism
  • Creatine Kinase / blood
  • Dietary Fats / adverse effects*
  • Doxorubicin / toxicity*
  • Fibrinogen / metabolism
  • Heart Diseases / chemically induced
  • Heart Diseases / pathology
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • L-Lactate Dehydrogenase / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Plasminogen Activator Inhibitor 1 / agonists
  • Plasminogen Activator Inhibitor 1 / blood
  • Protein C / antagonists & inhibitors
  • Protein C / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / blood
  • Trans Fatty Acids / adverse effects*
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • Triglycerides / blood
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation

Substances

  • Cardiotoxins
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Dietary Fats
  • Interleukin-6
  • NF-kappa B
  • Plasminogen Activator Inhibitor 1
  • Protein C
  • RNA, Messenger
  • Reactive Oxygen Species
  • Trans Fatty Acids
  • Transcription Factor RelA
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Doxorubicin
  • Antithrombin III
  • Fibrinogen
  • C-Reactive Protein
  • L-Lactate Dehydrogenase
  • Mitogen-Activated Protein Kinases
  • Creatine Kinase