title: Optimal dose-setting study of curcumin for improvement of left ventricular systolic function after myocardial infarction in rats.
abstract: 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.
authors.affiliation: Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yata, Suruga-ku, Shizuoka 422-8526, Japan; Shizuoka General Hospital, 4-27-1, Kitaando, Aoi-ku, Shizuoka 420-8527, Japan; Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, 1-1, Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sunagawa
authors.forename: Shogo
authors.initials: S
authors.lastname: Sono
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Katanasaka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Funamoto
authors.forename: Sae
authors.initials: S
authors.lastname: Hirano
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Yuya
authors.initials: Y
authors.lastname: Hojo
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Eriko
authors.initials: E
authors.lastname: Morimoto
authors.forename: Akira
authors.initials: A
authors.lastname: Marui
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Sakata
authors.forename: Morio
authors.initials: M
authors.lastname: Ueno
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kakeya
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Wada
authors.forename: Koji
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Morimoto
mesh_terms: D000818:Animals; D003474:Curcumin / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006333:Heart Failure / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013599:Systole; D016896:Treatment Outcome; D016277:Ventricular Function, Left; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors; D000099224:p300-CBP-Associated Factor
chemical_list: D003474:Curcumin; D004791:Enzyme Inhibitors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor