Abstract
Doxorubicin (Dox) is an effective anti-cancer drug, but its use is limited due to the adverse effect by inducing the 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 on Dox-induced cardiomyopathy (DIC). The mice were randomly divided into four groups: saline-control, Dox (15 mg/kg), Dox (15 mg/kg) plus Cilo (50 mg/kg), and Cilo (50 mg/kg). As results, the co-administration of Dox and Cilo significantly enhanced the left ventricular systolic function compared with Dox alone. In addition, Cilo treatment significantly reduced the Dox-induced perivascular fibrosis, collagen concentration, and connective growth factor expression in the hearts. Also, Cilo administration markedly reduced Dox-induced levels of serum B-type natriuretic peptide, dysferlin, high-mobility group protein B1 (HMGB1), toll-like receptor 4 (TLR4), nuclear factor-κB p65, and cyclooxygenase-2 (COX-2). Furthermore, Cilo treatment significantly reduced the Dox-induced oxidative stress by lowering the translocation of Nrf2 into the nucleus and the expression of NQO1, heme oxygenase (HO-1) and superoxide dismutase-1 (SOD-1). Our results suggest that Cilo may be the potential anti-fibrotic, anti-oxidative and anti-inflammatory drug for DIC.