aniseh javadi

A major clinical challenge in ischemic heart disease is the prevention of myocardial injury following ischemia/reperfusion (I/R). Application of natural pharmaceuticals seems to be clinically interesting due to their multiplex activities. Protective effects of troxerutin (TXR) in myocardial I/R injury have been ever demonstrated, nevertheless, the purpose of this study is to explore the role of mitochondrial adenosine triphosphate -sensitive potassium (mitoKATP) channels and toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway in cardioprotective effects of TXR against I/R injury in rats. Male Wistarrats (n=72, 250–300 g, 12 weeks old) were randomized into groups with/without I/R and/or TXR and 5-hydroxydecanoate(5-HD), alone or in combination. To induce I/Rmodel, the langendorff-perfused hearts were subjected to left anterior descending coronary artery (LAD) ligation and re-opening. TXR (150mg/kg/day) was administered for 4 weeks before I/R. Moreover, 5-HD (100 μM) was added to the perfusion solution before the ischemia. Finally, myocardial infarct size, LDH release, protein expression levels of TLR4 and NF-κB, and the levels of pro-inflammatory cytokines (TNF-α and IL-1β) were assessed. TXR preconditioning significantly reduced IS and LDH release (P<0.05). Furthermore, it decreased the expression of TLR4 and NF-κB and the levelof pro-inflammatory cytokines (P<0.05 to P<0.01). Inhibition of mitoKATPchannels by 5-HD significantly reversed the cardioprotective effects of TXR. This work shed some light on the knowledge about the mechanisms involved in the anti-inflammatory effect of TXR preconditioning in myocardial I/R injury. This effect may be partly mediated through mitoKATPchannels opening and subsequent suppression of the TLR4/NF-κB pathway.

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. 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. 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). 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.

Diabetic hearts are resistant to cardioprotection by ischemic-postconditioning (IPostC). Protection of diabetic hearts and finding related interfering mechanisms would have clinical benefits. This study investigated the combination effects of vildagliptin (Vilda) and IPostC on cardioprotection and the levels of autophagy and mitochondrial function following myocardial ischemia/reperfusion (I/R) injury in type-II diabetic rats.
Diabetes was established by high fat diet/low dose of streptozotocin and lasted for 12 weeks. The diabetic rats received Vilda (6 mg/kg/day, orally) for one month before I/R. Myocardial regional ischemia was induced through the ligation of left coronary artery, and IPostC was applied immediately at the onset of reperfusion. The infarct size was assessed by a computerised planimetry and left ventricles samples were harvested for cardiac mitochondrial function studies (ROS production, membrane potential and staining) and western blotting was used for determination of autophagy markers.
None of Vilda or IPostC but combination of them could significantly reduce the infarct size of diabetic hearts, comparing to control (P