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Iron is an essential element in many physiological processes due to its ability to easily convert between two oxidation states Fe(III)/Fe(II). However, at a pathological state, unbound iron may promote the production of highly toxic hydroxyl radicals via Fenton reaction, particularly when it is present in the excess.Iron chelators forming tight complexes with iron may prevent this reaction. In this study, novel synthetic 1-phenyl-3-methyl-4-acyl-pyrazol-5-ones were analyzed for their iron-chelating properties at four pathophysiologically relevant pH conditions (4.5-7.5) as well as for their effects on iron-based Fenton reaction. For the former competitive ferrozine spectrophotometric assay and for the latter HPLC method using salicylic acid as the indicator of hydroxyl radical production were used. All of the tested acylpyrazolones were efficient ferric chelators, however, their ferrous-chelating properties were clearly dependent on an acyl substitution. Interestingly, several acylpyrazolones had ferrous-chelating properties superior to those of the standard iron chelator - deferoxamine. Of particular interest is H2QpyQ, i.e. 2,6-bis[4(1-phenyl-3-methylpyrazol-5-one)carbonyl]pyridine, whose ferrous-chelating properties were increasing while pH was decreasing. In spite of large differences in ferrous chelation, a majority of the tested acylpyrazolones were powerful inhibitors of Fenton reaction as deferoxamine. In conclusion, the novel 1-phenyl-3-methyl-4-acyl-pyrazol-5-ones are efficient iron chelators and H2QpyQ may represent a prototype of specific iron chelators designed for chelation at acidic conditions in particular., (Copyright © 2014. Published by Elsevier Inc.)

Copper is an indispensable trace element for human body and the association between a disruption of copper homeostasis and a series of pathological states has been well documented. Flavonoids influence the human health in a complex way and the chelation of transient metal ions indisputably contributes to their mechanism of the action, however, the information about their copper-chelating properties have been sparse. This in vitro study was thus aimed at the detailed examination of flavonoids-copper interactions by two spectrophotometric assays at four (patho)physiologically relevant pH conditions (4.5-7.5), with the emphasis on the structure-activity relationship. The tested flavonoids were compared with the clinically used copper chelator, trientine. Most of the 26 flavonoids chelated copper ions, however, in a variable extent. Only flavones and flavonols were able to form stable complexes with both cupric and cuprous ions. The 3-hydroxy-4-keto group and 5,6,7-trihydroxyl group represented the most efficient chelation sites in flavonols and flavones, respectively, and the 2,3-double bond was essential for the stable copper chelation. Interestingly, the 3´,4´-dihydroxyl (catechol) group was associated only with a weak activity. Although none of the tested flavonoids were more potent than trientine at physiological or slightly acidic conditions, 3-hydroxyflavone, kaempferol and partly baicalein surpassed trientine at acidic conditions. Conclusively, flavonoids containing appropriate structural features were efficient copper chelators and some of them were even more potent than trientine under acidic conditions., (Copyright © 2014. Published by Elsevier Inc.)

Although a majority of studies related oxidative stress to cardiovascular diseases, the pathophysiological relevance has been remaining unknown. The aim of this study was to establish the relationship among different commonly used biomarkers of oxidative stress and cardiovascular dys/function in rats. A pathological state in many aspects similar to that of acute myocardial infarction was induced by administration of isoprenaline (100mg.kg(-1), s.c.) in Wistar:Han rats. Haemodynamic, biochemical and ECG parameters were measured in two sets of experiments: after 24hours and continuously during the first 2hours following the administration of isoprenaline. Serum cardiac troponin T (cTnT) correlated strongly with cardiac function, myocardial calcium levels, wet ventricles weight and relevant ECG parameters (T wave, R wave and J - junction - point amplitudes). However, only weak negative correlations were found for cTnT and total blood glutathione or serum vitamin C concentrations, while no significant associations were found with serum vitamin E and plasma TBARS. Although the oxidized form of glutathione correlated positively with heart rate, no correlation with the above-mentioned ECG parameters was found. However, correlations of in 8-isoprostane with both R wave and J-junction-point amplitudes were observed. Conclusively, more selective markers of oxidative stress may predict the functional status of the heart., (Copyright © 2014. Published by Elsevier Inc.)

Epidemiological, as well as most in vivo, studies suggest that flavonoids have a positive influence on various cardiovascular diseases. Traditionally, these effects were only attributed to their antioxidant activity, which has been extensively studied. Apart from the direct antioxidant properties, which include direct reactive oxygen species scavenging activity and transient metal chelation, this review reports on many other effects that in pharmacologically achievable concentrations may also be responsible for their positive cardiovascular influence. These include direct inhibition of some radical-forming enzymes (xanthine oxidase, NADPH oxidase, and lipoxygenases), decreased platelet aggregation and leukocyte adhesion, and vasodilatory properties. For each of the aforementioned effects different structural features are necessary. Briefly, a catecholic B-ring is necessary for scavenging activity; hydroxyl groups in an ortho position, the 3-hydroxy-4-keto group, or the 5-hydroxy-4-keto group enable iron chelation; planar conformation with the 4-keto group and 2,3-double bond is essential for inhibition of leukocyte adhesion and platelet aggregation; specific hydroxy-methoxy ortho conformation in ring B is necessary for the inhibition of NADPH oxidase; and the 4-keto group is a requisite for vasodilatory action. This review shows that positive cardiovascular effects of flavonoids are achieved by various flavonoids via the interaction with different targets., (Copyright 2010 Elsevier Inc. All rights reserved.)