title: Protective effect of cilostazol against doxorubicin-induced cardiomyopathy in mice.
abstract: Doxorubicin (Dox) is an effective anti-cancer drug, but its use is limited because of its adverse effect of inducing irreversible dilated cardiomyopathy. Cilostazol (Cilo), a potent phosphodiesterase III inhibitor, has been reported to have an anti-inflammatory effect. Here, we investigated whether Cilo has a protective effect against Dox-induced cardiomyopathy (DIC). Mice were randomly divided into four groups: saline control, Dox (15 mg/kg), Dox (15 mg/kg) plus Cilo (50mg/kg), and Cilo (50mg/kg). The results showed that the coadministration of Dox and Cilo significantly enhanced left-ventricular systolic function compared with Dox alone. In addition, Cilo treatment significantly reduced Dox-induced perivascular fibrosis, collagen concentration, and connective growth factor expression in the heart. Also, Cilo administration markedly reduced Dox-induced levels of serum B-type natriuretic peptide, dysferlin, high-mobility group protein B1, Toll-like receptor 4, nuclear factor-κB p65, and cyclooxygenase-2. Furthermore, Cilo treatment significantly reduced Dox-induced oxidative stress by lowering the translocation of Nrf2 into the nucleus and the expression of NQO1, heme oxygenase 1, and superoxide dismutase-1. Our results suggest that Cilo may be a potential antifibrotic, antioxidative, and anti-inflammatory drug for DIC.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Jin Sin
authors.initials: JS
authors.lastname: Koh
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Chin-ok
authors.initials: CO
authors.lastname: Yi
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Rok Won
authors.initials: RW
authors.lastname: Heo
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Jong-Wha
authors.initials: JW
authors.lastname: Ahn
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Jeong Rang
authors.initials: JR
authors.lastname: Park
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine,Jinju 660-751, Republic of Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea. Electronic address: jyhwang@gnu.ac.kr.
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Hwang
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea. Electronic address: anaroh@gnu.ac.kr.
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000077407:Cilostazol; D004317:Doxorubicin / Q000633:toxicity*; D004452:Echocardiography; D005355:Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D018696:Neuroprotective Agents; D013777:Tetrazoles; D004317:Doxorubicin; D000077407:Cilostazol
keywords: Cardiomyopathy; Cilostazol; Doxorubicin; Free radicals; Mouse