ABSTRACT
BACKGROUND: Diabetes mellitus is an independent risk factor for cardiovascular disease and is also associated with increased susceptibility to cardiovascular complications. It has been suggested that alterations in glucose metabolism and glucose flux via the aldose reductase pathway make the diabetic heart more sensitive to ischemic-reperfusion injury. Previous studies have found sulindac to have inhibitory and anti-inflammatory effects on aldose reductase. The use of aldose reductase inhibitors for the protection of ischemic myocardium is still in an exploratory state. OBJECTIVES: To evaluate the therapeutic potential of sulindac in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h) in diabetic and nondiabetic rats. METHODS: Diabetes was induced in rats by administering streptozotocin (45 mg/kg, intravenously). Myocardial infarction was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Sorbitol dehydrogenase levels in heart tissue, as well as lipid peroxide levels in serum and heart tissue, were estimated spectrophotometrically. RESULTS: Infarct size was increased in diabetic rats in comparison with normal rats. Pretreatment with sulindac significantly reduced infarct size, lipid peroxidation and sorbitol dehydrogenase levels in both diabetic and nondiabetic rats. The degree of cardioprotection was greater in diabetic rats than in nondiabetic rats. CONCLUSIONS: The present study indicates that the observed cardioprotection provided by sulindac in terms of reducing infarct size in normal rats may be due to its combined antioxidant and anti-inflammatory activities. The inhibition of aldose reductase may be responsible for the enhanced cardioprotection observed in diabetic rats treated with sulindac.
ABSTRACT
BACKGROUND: There is comprehensive experimental and clinical evidence that either exogenous supplementation of natural antioxidants or augmentation of endogenous antioxidants attenuates myocardial infarction. OBJECTIVES: To investigate the effects of chronic administration of silymarin against ischemia-reperfusion-induced myocardial infarction in rats. METHODS: Silymarin was administered orally to Wistar albino rats (200 g to 250 g) in three different doses (100 mg/kg, 250 mg/kg and 500 mg/kg), by gastric gavage for one week. At the end of this period, control (ischemia-reperfusion) groups and silymarin-treated groups were subjected to 30 min occlusion of the left anterior descending coronary artery and thereafter reperfused for 4 h. RESULTS: Ischemia-reperfusion resulted in significant cardiac necrosis, indicated by elevated levels of serum marker enzymes such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, lactate dehydrogenase, creatine kinase-isoenzyme and creatine kinase. A significant rise in the end products of myocardial lipid peroxides (malondialdehydes [MDAs]), loss of antioxidative enzymes (superoxide dismutase, catalase, glutathione S-transferase and reduced glutathione) and increased levels of myeloperoxidase in heart tissue were observed in the animals subjected to in vivo myocardial ischemia-reperfusion injury. Infarct size was measured by using the staining agent 2,3,5-triphenyltetrazolium chloride. A lead II electrocardiogram was monitored at various intervals throughout the experiment. DISCUSSION: The present study showed that silymarin protected the endogenous antioxidant enzymes, suppressed the neutrophil infiltration during ischemia-reperfusion and limited the infarct size, with concomitant reduction in serum MDA, tissue MDA and serum marker enzymes in rats subjected to 30 min coronary artery occlusion followed by 4 h of reperfusion. Pretreatment with silymarin also protected rat hearts from a further drop in mean arterial blood pressure during reperfusion, and restored heart rate at the end of the reperfusion period. CONCLUSIONS: The present study suggests that the phytochemical silymarin has cardioprotective activity against ischemia-reperfusion-induced myocardial infarction in rats.
ABSTRACT
It has been suggested that the beneficial effects of reperfusing the myocardium might be in part reversed by the occurrence of reperfusion injury. Oxidative stress was suggested to be implicating in the pathogenesis of ischemia-reperfusion (I/R) injury. Many antioxidative plants were shown to be cardioprotective in experimental models of myocardial ischemia-reperfusion (I/R) injury. The present study was designed to investigate the effects of pretreatment with alcoholic extract of Tinospora cordifolia in an in vivo rat model. The model adopted was that of surgically-induced myocardial ischemia, performed by means of left anterior descending coronary artery occlusion (LAD) for 30 min followed by reperfusion for another 4 h. Infarct size was measured by using the staining agent TTC (2,3,5-triphenyl tetrazolium chloride). Lipid peroxide levels in serum and in heart tissue were estimated spectrophotometrically by the methods developed by Yagi and Ohkawa et al. respectively. A lead II electrocardiogram was monitored at various intervals throughout the experiment. A dose dependent reduction in infarct size and in lipid peroxide levels of serum and heart tissue were observed with the prior treatment of T. cordifolia with various doses for 7 d compared to control animals. Hence, the present study suggests the cardioprotective activity of T. cordifolia in limiting ischemia-reperfusion induced myocardial infarction.
