Abstract
It is well known that cardiomyocyte apoptosis contributes to ischemic heart damage. There is also increasing evidence that the polyphenolic compounds of natural origin, such as anthocyanins, may attenuate ischemia/reperfusion injury though the mechanisms of such protection are not clear. Following our previous studies showing the effect of certain anthocyanins on cytochrome c redox state, mitochondrial functions, and ischemia-induced caspase activation in the heart, here we investigated whether these anthocyanins can rescue cardiac cells from death by the mechanism involving the reduction of cytosolic cytochrome c. Before global ischemia and reperfusion, isolated rat hearts were preloaded with cyanidin-3-O-glucoside (Cy3G) that has high cytochrome c-reducing capacity or pelargonidin-3-O-glucoside (Pg3G) that possesses low reducing activity. Cell death was evaluated assessing apoptosis by the TUNEL method or necrosis measuring the release of lactate dehydrogenase into perfusate. The perfusion of hearts with 20-μM Cy3G prevented ischemia/reperfusion-induced apoptosis of cardiomyocytes: the number of TUNEL-positive myocytes was decreased by 73% if compared with the untreated ischemic group. The same effect was observed measuring the activity of lactate dehydrogenase as the measure of necrosis: perfusion with 20-μM Cy3G reduced the level of LDH release into the perfusate to the control level. The perfusion of hearts with 20-μM Pg3G did not prevent ischemia/reperfusion-induced apoptosis as well as necrosis. Cy3G protected the rat heart from ischemia/reperfusion-induced apoptosis and necrosis; meanwhile, Pg3G did not exert any protective effect. The protective effect of Cy3G may be related due to its high capacity to reduce cytosolic cytochrome c.
Highlights
Heart diseases, such as myocardial infarction or ischemic heart failure, are the major causes of death in the developed countries, and the mortality rate from these diseases is still increasing
The perfusion of hearts with 20-μM Cy3G prevented ischemia/reperfusion-induced apoptosis of cardiomyocytes: the number of transferase-mediated dUTP nick end-labeling (TUNEL)-positive myocytes was decreased by 73% if compared with the untreated ischemic group
The same effect was observed measuring the activity of lactate dehydrogenase as the measure of necrosis: perfusion with 20-μM Cy3G reduced the level of LDH release into the perfusate to the control level
Summary
Heart diseases, such as myocardial infarction or ischemic heart failure, are the major causes of death in the developed countries, and the mortality rate from these diseases is still increasing. It has been shown that ischemia induces rapid cytochrome c release from mitochondria in the perfused heart [3,4,5]. We have recently shown that anthocyanins may protect the heart by the mechanism that is not related to their antioxidant activities: cyanidin-3-O-glucoside (Cy3G), anthocyanin exhibiting high cytochrome c-reducing activity, was found to prevent ischemia-induced caspase activation without blocking cytochrome c release from mitochondria, while another anthocyanin, pelargonidin-3-O-glucoside (Pg3G), possesing low cytochrome c reducing activity, did not exert any protective effect [15]. In this study, we sought to determine whether the anthocyanininduced blockage of caspase activation during ischemia may prevent cell death during reperfusion of the heart and whether this effect can be related to the capacity of anthocyanins to reduce cytochrome c
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