The clinical use of doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. The present study investigated the effects of scutellarin against DOX-induced cardiotoxicity in rats using pharmacodynamic and pharmacokinetic approaches. DOX (20 mg/kg) was injected intraperitoneally (i.p.) as a single dose, and scutellarin (5 mg/kg/day) was injected intravenously (i.v.) for 3 days. Rats treated with DOX showed acute cardiotoxicity as indicated by the elevated serum lactate dehydrogenase (LDH) activity (4057.8 ± 107.2 vs. 2032.7 ± 70.95), tissue malondialdehyde (MDA) level (2.083 ± 0.10 vs. 1.103 ± 0.09), cardiac troponin T (cTnT) concentration (0.1695 ± 0.0114 ng/mL), the decreased left ventricular ejection fraction (LVEF) (47.75 ± 15.79 vs. 78.72 ± 7.25) and left ventricular fractional shortening (LVFS) (20.66 ± 8.06 vs. 43.7 ± 6.76) compared with those of the control group. Cotreatment with scutellarin significantly decreased the LDH activity (2595.9 ± 72.73), MDA level (1.380 ± 0.06), cTnT concentration (0.0222 ± 0.0041 ng/m L), increased LVEF (76.70 ± 3.91) and LVFS (40.28 ± 3.68). Histopathological studies showed disruption of cardiac tissues in the DOX groups. Cotreatment with scutellarin reduced the damage to cardiac tissues. In the pharmacokinetic and tissue distribution study, scutellarin reduced the heart tissue exposure to DOX but did not change the AUC of plasma. These results suggest that scutellarin can protect against DOX-induced acute cardiotoxicity through its antioxidant activity and alterations of heart concentrations.
Keywords: Cardiotoxicity; Doxorubicin; Oxidative stress; Scutellarin; Tissue distribution.