Optimal Dose-Setting Study of Curcumin for Improvement of Left Ventricular Systolic Function After Myocardial Infarction in Rats

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  • Sunagawa Yoichi
    Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Japan Shizuoka General Hospital, Japan Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Japan
  • Sono Shogo
    Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Japan
  • Katanasaka Yasufumi
    Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Japan Shizuoka General Hospital, Japan Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Japan
  • Funamoto Masafumi
    Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Japan
  • Hirano Sae
    Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Japan Shizuoka Saiseikai General Hospital, Japan
  • Miyazaki Yusuke
    Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Japan
  • Hojo Yuya
    Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Japan
  • Suzuki Hidetoshi
    Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Japan
  • Morimoto Eriko
    Shizuoka General Hospital, Japan
  • Marui Akira
    Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Japan
  • Sakata Ryuzo
    Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Japan
  • Ueno Morio
    Department of Ophthalmology, Kyoto Prefectural University of Medicine, Japan
  • Kakeya Hideaki
    Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Wada Hiromichi
    Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Japan
  • Hasegawa Koji
    Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Japan
  • Morimoto Tatsuya
    Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Japan Shizuoka General Hospital, Japan Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Japan

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A natural p300-specific histone acetyltransferase inhibitor, curcumin, may have a therapeutic potential for heart failure. However, a study of curcumin to identify an appropriate dose for heart failure has yet to be performed. Rats were subjected to a left coronary artery ligation. One week later, rats with a moderate severity of myocardial infarction (MI) were randomly assigned to 4 groups receiving the following: a solvent as a control, a low dose of curcumin (0.5 mg∙kg−1∙day−1), a medium dose of curcumin (5 mg∙kg−1∙day−1), or a high dose of curcumin (50 mg∙kg−1∙day−1). Daily oral treatment was continued for 6 weeks. After treatment, left ventricular (LV) fractional shortening was dose-dependently improved in the high-dose (25.2% ± 1.6%, P < 0.001 vs. vehicle) and medium-dose (19.6% ± 2.4%) groups, but not in the low-dose group (15.5% ± 1.4%) compared with the vehicle group (15.1% ± 0.8%). The histological cardiomyocyte diameter and perivascular fibrosis as well as echocardiographic LV posterior wall thickness dose-dependently decreased in the groups receiving high and medium doses. The beneficial effects of oral curcumin on the post-MI LV systolic function are lower at 5 compared to 50 mg∙kg−1∙day−1 and disappear at 0.5 mg∙kg−1∙day−1. To clinically apply curcumin therapy for heart failure patients, a precise, optimal dose-setting study is required.

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