Original Contribution Expression of the longevity proteins by both red and white wines and their cardioprotective components, resveratrol, tyrosol, and hydroxytyrosol

Resveratrol increases longevity through SirT1, which is activated with NAD + supplied by an anti-aging enzyme PBEF. SirT1 interacts with an anti-aging transcription factor, FoxO1, which is negatively regulated by Akt. Since white wine could have similar health benefits as red wine, we determined if white wine and its cardioprotective components possess anti-aging properties by feeding rats with these compounds. The hearts expressed SirT, FoxO, and PBEF in the order of white wine N resveratrol N tyrosol N hydroxytyrosol N red wine, while cardioprotection shown by reduction of infarct size and cardiomyocyte apoptosis followed a different pattern: resveratrol N red wine N hydroxytyrosol N white wine N tyrosol, suggesting the existence of different signaling mechanisms for the induction of longevity and survival. Published by Elsevier Inc

Inhibited autophagy may contribute to heme toxicity in cardiomyoblast cells

Several groups have demonstrated that induction of heme-oxygenase-1 (HO-1) could protect the myocardium against ischemic events; however, heme accumulation could lead to toxicity. The aim of the present study was to investigate the role of autophagy in heme toxicity. H9c2 cardiomyoblast cells were treated with different dose of hemin or cobalt-protoporphyrin IX (CoPP) or vehicle. Cell viability was measured by MTT assay. DCF and MitoSOX staining was employed to detect reactive oxygen species. Western blot analysis was performed to analyse the levels of HO-1, certain autophagy related proteins and pro-caspase-3 as an apoptosis marker. To study the autophagic flux, CytoID staining was carried out and cells were analyzed by fluorescence microscope and flow cytometry. Decreased cell viability was detected at high dose of hemin and CoPP treated H9c2 cells in a dose-dependent manner. Furthermore, at concentration of the inducers used in the present study a significantly enhanced level of ROS were detected. As it was expected both treatments induced a robust elevation of HO-1 level. In addition, the Beclin-1- independent autophagy was significantly increased, but caused a defective autophagic flux with triggered activation of caspase-3. In conclusion, these results suggest that overexpression of HO-1 by high dose of hemin and CoPP can induce cell toxicity in H9c2 cells via enhanced ROS level and impaired autophagy

Beta-Carotene Affects the Effects of Heme Oxygenase-1 in Isolated, Ischemic/Reperfused Rat Hearts: Potential Role of the Iron

Beta-carotene (BC) is a well-known antioxidant. However, increasing evidence shows that under severe oxidative conditions, BC can become pro-oxidant, an effect that may be enhanced in the presence of iron (II). In our earlier studies, we observed that despite increasing heme oxygenase-1 (HO-1) levels in the heart, the protective effects of BC have been lost when it was used at a high concentration. Since iron releases from heme as a consequence of HO-1 activity, we hypothesized that the application of an iron-chelator (IC) would reverse the lost cardiac protection associated with an elevated HO-1 level. Thus, in the present study, we investigated the effects of desferrioxiamine (DFO) in isolated, ischemic/reperfused rat hearts after long-term treatment with vehicle or high-dose (HD) BC. Vehicle or 150 mg/bw kg daily doses of BC were administered to the rats for 4 weeks, and then their hearts were removed and subjected to 30 min of global ischemia (ISA) followed by 120 min of reperfusion (REP). During the experiments, cardiac function was registered, and at the end of the REP period, infarct size (IS) and HO-1 expression were measured. The results show that DFO treatment alone during REP significantly ameliorated postischemic cardiac function and decreased IS, although HO-1 expression was not increased significantly. In hearts isolated from BC-treated rats, no cardioprotective effects, despite an elevated HO-1 level, were observed, while DFO administration after ISA resulted in a mild improvement in heart function and IS. Our results suggest that iron could have a role whether BC exerts antioxidant or pro-oxidant effects in ISA/REP-injured hearts

Effects of Momordica charantia (Bitter Melon) on Ischemic Diabetic Myocardium

Objective: A rat model is here used to test a hypothesis that Momordica charantia (Bitter melon (BM)) extract favorably alters processes in cardiovascular tissue and is systemically relevant to the pathophysiology of type 2 diabetes (T2DM) and related cardiovascular disease. Methods: Male Lean and Zucker Obese (ZO) rats were gavage-treated for six weeks with 400 mg/kg body weight bitter melon (BM) extract suspended in mucin–water vehicle, or with vehicle (Control). Animals were segregated into four treatment groups, 10 animals in each group, according to strain (Lean or ZO) and treatment (Control or BM). Following six-week treatment periods, peripheral blood was collected from selected animals, followed by sacrifice, thoracotomy and mounting of isolated working heart setup. Results: Body mass of both Lean and ZO rats was unaffected by treatment, likewise, peripheral blood fasting glucose levels showed no significant treatment-related effects. However, some BM treatment-related improvement was noted in postischemic cardiac functions when Lean, BM-treated animals were compared to vehicle treated Lean control rats. Treatment of Lean, but not ZO, rats significantly reduced the magnitude of infarcted zone in isolated hearts subjected to 30 min of ischemia followed by 2 h of working mode reperfusion. Immunohistochemical demonstration of caspase-3 expression by isolated heart tissues subjected to 30 min of ischemia followed by 2 h of reperfusion, revealed significant correlation between BM treatment and reduced expression of this enzyme in hearts obtained from both Lean and ZO animals. The hierarchy and order of caspase-3 expression from highest to lowest was as follows: ZO rats receiving vehicle > ZO rats receiving BM extract > Lean rats treated receiving vehicle > Lean rats administered BM extract. Outcomes of analyses of peripheral blood content of cardiac-related analytics: with particular relevance to clinical application was a significant elevation in blood of ZO and ZO BM-treated, versus Lean rats of total cholesterol (high density lipoprotein HDL-c + low density lipoprotein LDL-c), with an inferred increase in HDL-c/LDL-c ratio—an outcome associated with decreased risk of atherosclerotic disease. Conclusions: BM extract failed to positively affect T2DM- and cardiovascular-related outcomes at a level suggesting use as a standalone treatment. Nevertheless, the encouraging effects of BM in enhancement of cardiac function, suppression of post-ischemic/reperfused infarct size extent and capacity to modulate serum cholesterol, will likely make it useful as an adjuvant therapy for the management of T2DM and related cardiovascular diseases

Retraction: Freshly Crushed Garlic is a Superior Cardioprotective Agent than Processed Garlic

Retraction: Freshly Crushed Garlic is a Superior Cardioprotective Agent than Processed Garli

Effects of long-term, low and high dose beta-carotene treatment in Zucker diabetic fatty rats: the role of HO-1

Abstract: Nowadays, there is a growing interest in compounds derived from plants as potential raw materials for drug development. One of the most studied compounds is beta-carotene (BC). Several clinical studies can be found investigating the cardiovascular effects of BC, however, all these results are controversial. There is increasing body of evidence showing that beside the well-known antioxidant properties, under strong oxidative circumstances BC could become prooxidant either. In this study we investigated the effects of long term, low- and high-dose BC treatment in ischemic/reperfused (ISA/REP) hearts isolated from zucker diabetic fatty (ZDF) rats. The animals were treated with various daily doses of BC for 4 weeks, and then hearts were isolated and subjected to 30 min of global ischemia (ISA) followed by 120 min of reperfusion (REP). Blood glucose levels were measured before, after two weeks and at the end of the treatment. In isolated hearts myocardial function was registered. At the end of reperfusion period infarctract size (IS) and heme oxygenase-1 (HO-1) expression were measured. The results show that low dose of BC treatment significantly improved postischemic recovery, which was reflected in a decreased IS. Interestingly, when BC was applied at high concentration, the observed protective effects were lost. Although, BC treatment increased HO-1 expression, we did not observe a better heart function and/or decreased IS in the high dose treated group. The glucose tolerance test showed concentration independent decrease in blood glucose levels. Our results suggest that long-term, low-dose BC treatment could be effective in the treatment of type-2-diabetes and related cardiovascular disease