Protective Role of Vitamin E. J Clin Med Res • 2012;4(3):190-196 intermembrane space, thus inducing apoptosis [32]. The re- duced adenosine triphosphate production could also result in other changes, such as myofilaments derangement, par- tial necrosis, intercalated disc dissociation and disintegration of filaments along with irregularities of the sarcomere [31]. The alterations of the sarcolemma in cells with end-stage de- generation were associated with loss of myofibrils, loss of junctional contacts with adjacent cells and marked surface irregularity. Remodelling of the cell surfaces is an important feature of the cellular response to the stimuli of hypertrophy or degeneration [33]. Myofibril loss and sarcomere disarray are the most obvious structural changes in human cardiomy- opathy and failing hearts [34]. The ANF-granules in the atria of rats treated with amio- darone alone were less concentrated and smaller in size. The enhancement of ANF synthesis in the cells to overcome car- diac overload, as in advanced heart failure, led to a reduction of the granule size with subsequent decrease in the levels of atrial ANF mRNA and plasma ANF in the course of the down regulation [35-37]. Concomitant administration of vitamin E with amioda- rone, showed a considerable preservation of atrial architec- ture. The protective effects of vitamin E against ultrastruc- tural changes in other tissues, such as those of the lung and liver, have been reported [38, 19, 20]. The possible mecha- nism of the protective effect of vitamin E on cardiomyocytes may be the result of several factors, including decreased cel- lular amiodarone accumulation, decreased fat rancidisation, increased membrane stabilisation, altered profibrotic gene expression, free radical scavenging and decreased apoptosis [39-42]. Although the protective benefit of vitamin E co-admin- istration against amiodarone-induced cardiomyotoxicity is clearly observed in this report, the exact mechanism of this protection is not yet clear. The worrisome mechanism is that Vitamin E may negatively affect the antiarrhythmic ef- ficacy of amiodarone. Furthermore, replicating the beneficial effects of vitamin E as antioxidant usually fails in clinical studies. The exact explanation for these conflicting results is not yet evident. However, Zoulin made a very interest- ing observation when he compared the results from animal and in vitro studies with results from human clinical trials. He found that the animals used in the antioxidative stress trials were already at abnormal levels of stress, whereas high-powered clinical trials lacked the confounding effect of stress and revealed no benefit or adverse outcome. However, smaller clinical studies involving patients with abnormal levels of stress, for example, studies involving diabetic pa- tients, show some benefits. He concluded that antioxidant in- tervention during the so-called (WOPS) “Window Period for Oxidative Stress Attenuating Intervention” will show maxi- mum benefit, whereas intervention outside this window will show no benefit or may even cause harm [43, 44]. Cardiac patients who require amiodarone therapy usually suffer from advanced heart disease, and their cardiac cells are expected to be under an abnormally high level of oxidative stress. Adding amiodarone to their drug regime, though effective in reducing arrhythmias, may lead to further progressive loss of myocardium and death due to pump failure rather than the arrhythmias themselves [45-47]. Therefore, it would be wise to consider adding antioxidant agents such as vitamin E when amiodarone use is contemplated. 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