Protective mechanisms of resveratrol against ischemia-reperfusion-induced damage in hearts obtained from Zucker obese rats: the role of GLUT-4 and endothelin. Am J Physiol Heart Circ Physiol 294: H859-H866, 2008. First published December 7, 2007 doi:10.1152/ajpheart.01048.2007.-The resveratrol-induced cardiac protection was studied in Zucker obese rats. Rats were divided into five groups: group 1, lean control; group 2, obese control (OC); group 3, obese rats treated orally with 5 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 of resveratrol (OR) for 2 wk; group 4, obese rats received 10% glucose solution ad libitum for 3 wk (OG); and group 5, obese rats received 10% glucose for 3 wk and resveratrol (OGR) during the 2nd and 3rd wk. Body weight, serum glucose, and insulin were measured, and then hearts were isolated and subjected to 30 min of ischemia followed by 120 min of reperfusion. Heart rate, coronary flow, aortic flow, developed pressure, the incidence of reperfusioninduced ventricular fibrillation, and infarct size were measured. Resveratrol reduced body weight and serum glucose in the OR compared with the OC values (414 Ϯ 10 g and 7.08 Ϯ 0.41 mmol/l, respectively, to 378 Ϯ 12 g and 6.11 Ϯ 0.44 mmol/l), but insulin levels were unchanged. The same results were obtained for the OG vs. OGR group. Resveratrol improved postischemic cardiac function in the presence or absence of glucose intake compared with the resveratrolfree group. The incidence of ventricular fibrillation and infarct size was reduced by 83 and 20% in the OR group, and 67 and 16% in the OGR group, compared with the OC and OG groups, respectively. Resveratrol increased GLUT-4 expression and reduced endothelin expression and cardiac apoptosis in ischemic-reperfused hearts in the presence or absence of glucose intake. Thus the protective effect of resveratrol could be related to its direct effects on the heart. heart; ischemia-reperfusion; diabetes; rat IN THE PAST THREE DECADES, an explosive increase in the number of people diagnosed with diabetes was seen worldwide (7, 48).

Cardioprotective mechanisms of Prunus cerasus (sour cherry) seed extract against ischemia-reperfusion-induced damage in isolated rat hearts. Am J Physiol Heart Circ Physiol 291: H1329 -H1336, 2006. First published April 14, 2006 doi:10.1152/ajpheart.01243.2005The effects of kernel extract obtained from sour cherry (Prunus cerasus) seed on the postischemic cardiac recovery were studied in isolated working rat hearts. Rats were treated with various daily doses of the extract for 14 days, and hearts were then isolated and subjected to 30 min of global ischemia followed by 120 min of reperfusion. The incidence of ventricular fibrillation (VF) and tachycardia (VT) fell from their control values of 92% and 100% to 50% (not significant) and 58% (not significant), 17% (P Ͻ 0.05), and 25% (P Ͻ 0.05) with the doses of 10 mg/kg and 30 mg/kg of the extract, respectively. Lower concentrations of the extract (1 and 5 mg/kg) failed to significantly reduce the incidence of VF and VT during reperfusion. Sour cherry seed kernel extract (10 and 30 mg/kg) significantly improved the postischemic recovery of cardiac function (coronary flow, aortic flow, and left ventricular developed pressure) during reperfusion. We have also demonstrated that the extract-induced protection in cardiac function significantly reflected in a reduction of infarct size. Immunohistochemistry indicates that a reduction in caspase-3 activity and apoptotic cells by the extract, beside other potential action mechanisms of proanthocyanidin, trans-resveratrol, and flavonoid components of the extract, could be responsible for the cardioprotection in ischemic-reperfused myocardium.

A plant-based diet reduces the risk for the development of several chronic diseases, such as ischemic heart disease or cancer due to natural compounds found in plants. Numerous cereals, berries, fruits, and vegetables, including sour cherry (Prunus cerasus), which is a favored fruit worldwide, contain biological active components. The antioxidant components of the sour cherry seed kernel have not been investigated until now. The aim of our study was to isolate and analyze the bioactive constituents of sour cherry seed kernel. We separated the oil fraction of the kernel; then the remaining solid fraction was dried, and the oil-free kernel extract was further analyzed. Our results show that sour cherry seed kernel oil contains vegetable oils including unsaturated fatty acids, oleic acids, alpha-tocopherol, tocotrienols, and tocopherol-like components. The components of the solid fraction include various bioactive structures such as polyphenols, flavonoids, vegetable acids, and pro- and anthocyanidins, which could have useful therapeutic effects in the prevention of various vascular diseases.

Heme oxygenase-1 (HO-1)-dependent carbon monoxide (CO) production related to reperfusioninduced ventricular fibrillation (VF) was studied in HO-1 wild-type (+/+), heterozygous (+/−), and homozygous (−/−) isolated ischemic/reperfused mouse heart. In HO-1 homozygous myocardium, under aerobic conditions, HO-1 enzyme activity, HO-1 mRNA, and protein expression were not detected in comparison with aerobically perfused wild-type and heterozygous myocardium. In wild-type, HO-1 hetero-and homozygous hearts subjected to 20 min ischemia followed by 2 h of reperfusion, the expression of HO-1 mRNA, protein, and HO-1 enzyme activity was detected in various degrees. A reduction in the expression of HO-1 mRNA, protein, and enzyme activity in fibrillated wild-type and heterozygous myocardium was observed. In reperfused/nonfibrillated wild-type and heterozygous hearts, a reduction in HO-1 mRNA, protein expression, and HO-1 enzyme activity was not observed, indicating that changes in HO-1 mRNA, protein, and enzyme activity could be related to the development of VF. These changes were reflected in the HO-1-related endogenous CO production measured by gas chromatography. In HO-1 knockout ischemic/reperfused myocardium, all hearts showed VF, and no detection in HO-1 mRNA, protein, and enzyme activity was observed. Thus, interventions that are able to increase endogenous CO may prevent the development of VF.Key words: heme oxygenase-1 expression • ischemia/reperfusion • HO-1 knockout mouse hearts t has been proposed that most cases of sudden cardiac death may result from ischemia and/or reperfusion-induced ventricular fibrillation (VF; 1-3). Interest in the development and pharmacological control of reperfusion-induced VF has been stimulated by the realization that such arrhythmias may occur under a number of pathological and clinical circumstances, including the spontaneous relief of coronary artery spasm (4). There is considerable controversy over the mechanisms responsible for the induction of these arrhythmias, and a number of I different mechanisms have been suggested (5), but the two major factors proposed and generally accepted to explain reperfusion-induced injury and VF are 1) calcium overload and 2) free radical formation. Examples of oxidative stress-related diseases include reperfusion-induced injury occurring after tissue ischemia or stroke and inflammatory processes, such as arthritis (6). Heme oxygenase (HO) catalyzes the rate-limiting step in the oxidative degradation of heme to biliverdin and carbon monoxide (CO; ref 7). Three isozymes of HO have been identified and cloned; HO-1, an inducible form, HO-2, and HO-3 constitutive forms (8). Studies demonstrate that HO-1 is induced in response to various interventions causing oxidative stress, including ultraviolet irradiation, hypoxia, and ischemia (6,(9)(10)(11)(12).In previous studies, we observed a reduction in HO-1 mRNA expression, its protein, and enzyme activity in ischemic/reperfused fibrillated myocardium but not in nonfibrillated ischemic/reperfused hear...