title: Dietary trans fats enhance doxorubicin-induced cardiotoxicity in mice.
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.
authors.affiliation: Dept. of Health and Nutrition Biotechnology, Asia Univ., Taichung City, Taiwan.
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Mong
authors.affiliation: Dept. of Respiratory Therapy, China Medical Univ., Taichung City, Taiwan.
authors.forename: Te-Chun
authors.initials: TC
authors.lastname: Hsia
authors.affiliation: Dept. of Health and Nutrition Biotechnology, Asia Univ., Taichung City, Taiwan.|Dept. of Nutrition, China Medical Univ., Taichung City, Taiwan.
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Yin
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000037:antagonists & inhibitors / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D054715:Cardiotoxins / Q000633:toxicity*; D018932:Chemokine CCL2 / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D004041:Dietary Fats / Q000009:adverse effects*; D004317:Doxorubicin / Q000633:toxicity*; D005340:Fibrinogen / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced / Q000473:pathology; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000819:agonists / Q000097:blood; D011486:Protein C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000097:blood; D044242:Trans Fatty Acids / Q000009:adverse effects*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D054715:Cardiotoxins; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004041:Dietary Fats; D015850:Interleukin-6; D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D044242:Trans Fatty Acids; D051996:Transcription Factor RelA; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004317:Doxorubicin; D000990:Antithrombin III; D005340:Fibrinogen; D002097:C-Reactive Protein; D007770:L-Lactate Dehydrogenase; D020928:Mitogen-Activated Protein Kinases; D003402:Creatine Kinase
keywords: MAPK; NF-κB; cardiac injury; coagulation; doxorubicin; trans fat