Abstract
The prevention of doxorubicin (DXR)โinduced cardiotoxicity may be helpful to improve future DXR therapy. The aim of this study was to investigate the cardioโprotective effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, on DXRโinduced cardiotoxicity. Rats were divided into three groups and treated with saline, DXR and DXR + CAPE. Rats were treated with CAPE (10 ยตmol kg^โ1^ day^โ1^ i.p.) or saline starting 2 days before a single dose of DXR (20 mg kg^โ1^ i.p.). Ten days later, haemodynamic measurements were performed and the hearts were excised for biochemical analyses and microscopic examination. The heart rate and mean blood pressure were higher and the pulse pressure was lower in the DXR group than in the other two groups. The administration of DXR alone resulted in higher myeloperoxidase activity, lipid peroxidation and protein carbonyl content than in the other groups. The activities of superoxide dismutase and catalase were higher in DXR and DXR + CAPE groups than in the saline group. Rats in the DXR + CAPE group had increased catalase activity in comparison with the DXR group and high glutathione peroxidase activity in comparison with the other two groups. There was severe disruption of mitochondrial ๏ฌne structure in the electron microscopy of the DXR group. In contrast, myocardial microscopy appeared nearly normal in the DXR + CAPE group (as de๏ฌned at the electron microscopic level). In light of these in vivo haemodynamic, enzymatic and morphological results, we conclude that CAPE pretreatment signi๏ฌcantly attenuated DXRโinduced cardiac injury, possibly with its antioxidant effects. Copyright ยฉ 2004 John Wiley & Sons, Ltd.