Abstract
The clinical application of doxorubicin is limited by its cardiotoxicity. The present study investigated the effect of valsartan on doxorubicin-induced cardiotoxicity in rats. Rats were divided into 6 groups: control, control + valsartan (10 mg/kg, for 14 days, orally), doxorubicin-treated (2.5 mg/kg, 3 times/week for 2 weeks, intraperitoneally), valsartan then doxorubicin, valsartan + doxorubicin, and doxorubicin then valsartan. ECG, isolated heart, lipid peroxidation (thiobaribituric acid reactive substances (TBARS)), total antioxidant capacity (TAC), and Bax, Bcl-2, and senescence marker protein 30 (SMP30) gene expression were measured in cardiac tissue. Blood samples were collected to measure lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB). Doxorubicin significantly increased LDH, CK-MB, TBARS, heart rate (HR), Bax gene expression, and -dP/dt(max) and decreased TAC, Bcl-2 and SMP30 gene expression, left ventricular developed pressure (LVDP), and +dP/dt(max). Also, doxorubicin lengthened ST, QT, and QTc intervals. Concurrent or post-but not pre-treatment of doxorubicin-treated rats with valsartan reduced LDH, CK-MB, TBARS, HR, Bax gene expression, -dP/dt(max), and ST, QT, and QTc intervals and increased TAC, Bcl-2 and SMP30 gene expression, LVDP, and +dP/dt(max). Therefore, we conclude that concurrent or post-but not pre-treatment of doxorubicin-induced rats with valsartan attenuated doxorubicin-induced cardiotoxicity through inhibiting oxidative stress, apoptosis, and senescence.