Olive Leaf Extract and a-Tocopherol Combination Therapy Attenuates Doxorubicin Induced Cardiotoxicity in Rats

Abstract
Background: Cardiotoxicity is a serious side effect of Doxorubicin (DOX), which is a very effective drug used in the management of several malignancies. Oxidative stress is thought to play the major role in DOX toxicity. Several antioxidants such as vitamin E and anti-inflammatory sub-stances like Olive Leaf Extract (OLE) used to attenuate DOX toxicity.
Aim: This experimental study tests the hypothesis that, co-administration of both Vit-E and OLE will have a synergistic and/or additive effects, and that their concomitant use is better than using either alone in alleviating DOX Induced Cardiac Toxicity (DICT) in rats.
Material and Methods: For the first 2 weeks, 4 groups of Wistar rats (n=8 in each) received intraperitoneal (i.p) DOX (total 20mg/kg) injections (DOX groups). Three of them also received either daily OLE: 500mg/kg BW or daily a-tocopherol 100mg/kg BW, or both for a period of 4 weeks. A control group of rats that received only i.p. saline was also included. All groups were tested for parameters of myocardial contrac-tility and left ventricular function (LVDP, LVEDP and dp/dt max), Aortic Pressure (AoP), markers of myocardial tissue injury (cTnI, LDH, AST and ANP), and oxidative stress state (MDA, GSH, GPx and SOD).
Results: Combined OLE and Vit-E therapy with DOX improved Myocardial Contractility (MC), Left Ventricular Functions (LVF) and reduces Aortic Pressure (AoP), it also protected from DOX induced cardiac tissue injury and atten-uated the accompanying oxidative stress state better than either alone.
Conclusion: The results of the present study confirm the beneficial effects of combined OLE and Vit-E therapy in ameliorating DICT in rats.