The Effects of Long-Term, Low- and High-Dose Beta-Carotene Treatment in Zucker Diabetic Fatty Rats: The Role of HO-1.

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.

Synthesis, in Vitro Biological Evaluation, and Oxidative Transformation of New Flavonol Derivatives: The Possible Role of the Phenyl-N,N-Dimethylamino Group.

Six new flavonols (6a⁻f) were synthesized with Claisen⁻Schmidt and Suzuki reactions and they were fully characterized by spectroscopic methods. In order to evaluate their antioxidant activities, their oxygen radical absorption capacity and ferric reducing antioxidant power were measured, along with their free radical scavenging activity against 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and 2,2-diphenyl-1-picrylhydrazylradicals. In addition, their cytotoxicity on H9c2 cardiomyoblast cells was also assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Compounds bearing the phenyl-N,N-dimethylamino group (6a, 6c, and 6e) exhibited promising antioxidant potency and did not have any cytotoxic effect. After a consideration of these data, the oxidative transformation of the 6c compound was investigated in vitro with a chemical Fenton reaction and the identification of the formed oxidation products was performed by mass spectrometry. Two potential metabolites were detected. Based on these results, compound 6c can be a model compound for future developments. Overall, this work has proved the involvement of the phenyl-N,N-dimethylamino group in the antioxidant activity of flavonols.

Antioxidant Properties and Oxidative Transformation of Different Chromone Derivatives.

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.

A new, vasoactive hybrid aspirin containing nitrogen monoxide-releasing molsidomine moiety.

Ischemic heart conditions are among the main causes of sudden cardiac death worldwide. One of the strategies for avoiding myocardial infarction is the low-dose, prophylactic use of acetylsalicylic acid (ASA), an inhibitor of platelet aggregation. To avoid the gastrointestinal damage, ASA prodrugs bearing nitric oxide (NO)-donating moiety covalently conjugated to ASA have been synthesized and evaluated extensively worldwide. Herein the synthesis of a new hybrid ASA ester covalently attached to the NO donor linsidomine, an active metabolite of molsidomine (MOL) is reported. Cell viability assay and hemolysis tests were performed in H9c2 cells and rat erythrocytes, respectively. Our new compound, the ERJ-500 not affected negatively the viability of living cells in the concentration range of 100 nM to 100 µM. Using the ex vivo Langendorff method on hearts originated from female rats, compound ERJ-500 displayed a dose-dependent, outwashable vasodilative effect in coronary arteries. Vasodilation was observed on isolated working heart model as well, with elevated stroke volume in hearts treated with ERJ-500. Furthermore, a decreased infarct size was also noticed in ERJ-500 treated hearts after ischemia/reperfusion. Based on these observations it can be expected that our new hybrid ASA may contribute to new pharmacological tool in the therapy of ischemic heart conditions and associated syndromes.

Dataset on structure, stability and myocardial effects of a new hybrid aspirin containing nitrogen monoxide-releasing molsidomine moiety.

Herein 1H and 13C NMR spectra of ERJ-500, a new hybrid aspirin derivative, covalently conjugated to nitrogen monoxide donor linsidomine are presented as well as NMR spectra of its synthetic intermediate compounds. HPLC-MS measurements data are also included, demonstrating the stability of the linsidomine-aspirin hybrid in oxidation reactions. This data article also concerns miscellaneous myocardial parameters of isolated rat hearts as a complementation of the tables shown in the paper entitled "A new, vasoactive hybrid aspirin containing nitrogen monoxide-releasing molsidomine moiety" Szoke et al., 2019. Column tables represent data of aorta flow, aortic pressure, derivated aortic pressure and cardiac output.