Details

Autor(en) / Beteiligte

• Koh, Jin Sin
• Yi, Chin-ok
• Heo, Rok Won
• Ahn, Jong-Wha
• Park, Jeong Rang
• Lee, Jung Eun
• Kim, Jung-Hwan
• Hwang, Jin-Yong
• Roh, Gu Seob

Titel

Protective effect of cilostazol against doxorubicin-induced cardiomyopathy in mice

Ist Teil von

• Free radical biology & medicine, 2015-12, Vol.89, p.54-61

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 (15mg/kg), Dox (15mg/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. •Doxorubicin decreases systolic function of the left ventricle.•Cilostazol, a potent phosphodiesterase III inhibitor, protects against doxorubicin-induced cardiomyopathy.•Cilostazol has anti-inflammatory, antifibrotic, and antioxidative effects in doxorubicin-treated hearts.