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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.

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 an increasing body of evidence showing that besides the well-known antioxidant properties, under strong oxidative circumstances, BC could become prooxidant as well. 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, the myocardial function was registered. At the end of the reperfusion period, the infarct size (IS) and heme oxygenase-1 (HO-1) expression were measured. The results showed that a low dose of BC treatment significantly improved postischemic recovery, which was reflected in a decreased IS. Interestingly, when BC was applied at high concentrations, 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. Glucose tolerance tests showed a 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 diseases.

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.

The present report describes outcomes of animal studies conducted to determine the systemic and dermal toxicity of Prunus cerasus (sour cherry) seed kernel contents; and a separate evaluation of the photoprotective capacity of the kernel oil fraction. B6 mice and Hartley guinea-pigs were used for these experiments. Dosage groups of 6–8 animals were administered whole kernel meal in a dose range of 0–3000 mg/kg by gavage for 8 days, following which they were killed. The liver and kidney weights were recorded and histological examination performed on sections of these organs. Kidney function was assessed as blood urea nitrogen and creatinine and liver function by measurement of serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase. Dermal toxicity was evaluated in a Hartley guinea-pig model by comparing UVB-irradiated shaved skin to which the kernel oil had been applied with distilled water controls. In conclusion, no evidence of toxicity was observed to result from the consumption or dermal application of sour cherry seed kernel in the dose range at which it is likely to be used in foods or healthcare. Moreover, it was shown to have a powerful capacity to protect skin from UV damage. These results suggest it will prove to be a highly safe and effective addition to a wide range of products for general use. Copyright © 2011 John Wiley & Sons, Ltd.

β-carotene (BC), a lipid-soluble tetraterpene precursor to vitamin A, widely distributed in plants, including many used in human diet, has well-known health-enhancing properties, including reducing risk of and treatment for certain diseases. Nevertheless, BC may also act to promote disease through the activity of BC derivatives that form in the presence of external toxicants such as cigarette smoke and endogenously-produced reactive oxygen species. The present investigation evaluates the dose-dependent cardioprotective and possibly harmful properties of BC in a rat model. Adult male rats were gavage-fed BC for 4 weeks, at dosages of either 0, 30 or 150mg/kg/day. Then, hearts excised from the animals were mounted in a “working heart” apparatus and subjected to 30min of global ischemia, followed by 120min of reperfusion. A panel of cardiac functional evaluations was conducted on each heart. Infarct size and total antioxidant capacity of the myocardium were assessed. Heart tissue content of heme oxygenase-1 (HO-1) by Western blot analysis; and potential direct cytotoxic effects of BC by MTT assay were evaluated. Hearts taken from rats receiving 30mg/kg/day BC exhibited significantly improved heart function at lower reperfusion times, but lost this protection at higher BC dosage and longer reperfusion times. Myocardial HO-1 content was significantly elevated dose-responsively to both BC dosage. Finally, in vitro evaluation of BC on H9c2 cells showed that the agent significantly improved vitality of these cells in a dose range of 2.5–10μM.Although data presented here do not allow for a comprehensive mechanistic explanation for reduced cardioprotection at high dose BC, it is speculated that since Fe2+ produced as a metabolite of HO-1 activity, may determine whether BC acts as an antioxidant or prooxidant agent, the strong induction of this enzyme in response to ischemia/reperfusion-induced oxidative stress may account for the high-dose BC loss of cardioprotection.

Nowadays, there is an increase in the application of natural products for the prevention of different disorders or adjuvant substances next to pharmacological treatment. Phytochemicals include different chromone derivatives, which possess a wide spectrum of biological activity. The aim of the present study was the investigation of the antioxidant activity, cytotoxicity and oxidative transformation of nine chromone derivatives. First, we investigated the radical scavenging activity (ABTS), the oxygen radical absorption capacity (ORAC) and the ferric reducing antioxidant power (FRAP) of the investigated molecules. The cytotoxic effects of the compounds were tested on H9c2 cell cultures by the MTT assay. Each compound showed a significant ORAC value compared to the reference. However, the compound 865 possess significantly higher FRAP and ABTS activity in comparison with the reference and other tested molecules, respectively. Based on these assays, the compound 865 was selected for further analysis. In these experiments, we investigated the oxidative metabolism of the compound in vitro. The molecule was oxidized by the Fenton reaction, artificial porphyrin and electrochemistry; then, the formed products were identified by mass spectrometry. Four possible metabolites were detected. The results revealed the compound 865 to possess good antioxidant properties and to be stable metabolically; hence, it is worth investigating its effects in vivo.

International audience; Autophagy is an intracellular bulk degradation process for elimination of damaged macromolecules and organelles. In the past decades, the scientific community has gained increasingly detailed understanding of the role of autophagy in myocardial homeostasis, although still many controversies remain. In the ischemic myocardium, autophagy appears to be beneficial for survival, whereas upon reperfusion the process may induce cell death. However, the overall effect of autophagy seems to depend on the duration and intensity of stress, as along with the extent of autophagy within myocardial tissue. Reperfusion of an ischemic heart maybe harmful, but it is an essential process for myocardial survival. One of the major adverse consequences of reperfusion is the occurrence of ventricular fibrillation (VF). In the present study, we investigated the possible connection between autophagy and VF. Isolated mouse hearts were subjected to ischemia/reperfusion (I/R) and divided into two groups based on the development of VF at the beginning of reperfusion. Western blot analysis was conducted for autophagy-associated proteins LC3B, ATG-5, ATG-7, ATG-12, Bcl-2 and Beclin-1 proteins. Significantly higher level of Beclin-1 and LC3B-II/LC3B-I ratio (both definitive autophagy biomarkers) was observed in the fibrillated myocardium, versus tissue from the nonfibrillated hearts. Interestingly, although Bcl-2 is a major regulator of Beclin-1, level of this protein was not significantly altered in tissue from fibrillated, versus non-fibrillated hearts. Moreover, Atg7 expression showed a trend, albeit non-significant, towards elevation in fibrillated versus non-fibrillated hearts. Results of the present investigation demonstrate a possible link between VF and autophagy. Studies by authors of this report to evaluate potential etiologic relationships between the two processes are ongoing.

The present report describes outcomes of animal studies conducted to determine the systemic and dermal toxicity of Prunus cerasus (sour cherry) seed kernel contents; and a separate evaluation of the photoprotective capacity of the kernel oil fraction. B6 mice and Hartley guinea-pigs were used for these experiments. Dosage groups of 6-8 animals were administered whole kernel meal in a dose range of 0-3000 mg/kg by gavage for 8 days, following which they were killed. The liver and kidney weights were recorded and histological examination performed on sections of these organs. Kidney function was assessed as blood urea nitrogen and creatinine and liver function by measurement of serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase. Dermal toxicity was evaluated in a Hartley guinea-pig model by comparing UVB-irradiated shaved skin to which the kernel oil had been applied with distilled water controls. In conclusion, no evidence of toxicity was observed to result from the consumption or dermal application of sour cherry seed kernel in the dose range at which it is likely to be used in foods or healthcare. Moreover, it was shown to have a powerful capacity to protect skin from UV damage. These results suggest it will prove to be a highly safe and effective addition to a wide range of products for general use.