Combined Preconditioning With Cinnamon Extract and Aerobic Training Reduce Oxidative Stress in a Rat Model of Myocardial Reperfusion Injury

Introduction Death due to coronary artery disease is at the forefront of mortality worldwide, especially in industrialized societies. Acute myocardial infarction, which is resulted from intense interruption of blood flow to the myocardial tissue, is the most serious and often fatal outcome of the coronary diseases (1,2). Rapid and immediate establishment of reperfusion is completely required for the ischemic myocardium survival. In patients with coronary obstruction, reperfusion is performed by protocols such as thrombolysis or angioplasty. However, it per se has additional deleterious impacts, collectively referred to as reperfusion injury (2,3). The reperfusion injury is more severe than ischemic injury, leading to necrosis, apoptosis, and irreversible damage or even cell death (3). Thus, mortality in patients undergoing myocardial reperfusion is still high and therefore finding new therapeutic strategies to protect the heart against this phenomenon seems to be important. The pathophysiology of reperfusion injury is complex. At early reperfusion phase following prolonged myocardial ischemia, the oxidative stress is overproduced by different ways (3,4). When molecular oxygen is reintroduced to the previously ischemic myocardium, it goes under repetitive reduction which produces superoxide radicals. In addition, potent free radicals like superoxide anions, hydroxyl radicals, and peroxynitrite have an essential role in reperfusion injury phenotype (5). Free radicals initiate the injury by the opening of mitochondrial permeability transition pores, acting as a chemoattractant for neutrophils, and inducing the dysfunction of sarcoplasmic reticulum. All of these changes lead to intracellular calcium overload, cell membrane dissipation due to high lipid-peroxidation, denaturation of antioxidative enzymes and direct oxidative damages to DNA (5-7). Researchers are testing different ways to postpone Abstract Objectives: Ischemic heart disease is the principal cause of mortality worldwide. Using natural strategies to prevent this disease is very important. Therefore, the current study aimed to evaluate the combined effects of the cinnamon extract and aerobic exercise on oxidative stress following myocardial ischemia/reperfusion (I/R) injury. Materials and Methods: Male Wistar rats weighing 250-300 g were randomly divided into 4 groups (6 rats each) including control, cinnamon extract, aerobic exercise, and a combination of cinnamon and exercise. The aerobic exercise was performed on a treadmill and the cinnamon extract was administered by gavage for a month. In addition, the isolated hearts of the rats received global ischemia (30 minutes) and reperfusion (60 minutes) in order to induce I/R injury. Lactate dehydrogenase (the indicator of tissue damage), the marker of lipid peroxidation (malondialdehyde), and antioxidative enzymes (i.e., superoxide-dismutase and glutathione-peroxidase) were measured with specific kits and spectrophotometric methods on samples obtained from the ischemic tissues. Results: Based on the results, lactate dehydrogenase level significantly decreased in the group receiving a combination of cinnamon and aerobic exercise compared to the control group (P < 0.05). Further, both aerobic exercise and cinnamon extract significantly increased the values of antioxidant enzymes and this effect was greater in combination therapy compared to the individual treatments. However, the amount of malondialdehyde in the exercise group and in the combined treatment significantly reduced compared to that of the control groups (P < 0.05). Conclusions: A combination of aerobic training with cinnamon supplementation had better cardioprotective influences. Accordingly, cinnamon may increase the aerobic exercise potency in enhancing the heart antioxidant capacity against oxidative insult in reperfusion injury.