A Comparative Study of the Inhibitory Effect of Some Flavonoids and a Conjugate of Taxifolin with Glyoxylic Acid on the Oxidative Burst of Neutrophils.

During the storage, processing, and digestion of flavonoid-rich foods and beverages, a condensation of flavonoids with toxic carbonyl compounds occurs. The effect of the resulting products on cells remains largely unknown. The aim of the present study was to evaluate the effects of quercetin, taxifolin, catechin, eriodictyol, hesperetin, naringenin, and a condensation product of taxifolin with glyoxylic acid on the oxidative burst of neutrophils. It was found that the flavonoids and the condensation product inhibited the total production of ROS. Flavonoids decreased both the intra and extracellular ROS production. The condensation product had no effect on intracellular ROS production but effectively inhibited the extracellular production of ROS. Thus, the condensation of flavonoids with toxic carbonyl compounds may lead to the formation of compounds exhibiting potent inhibitory effects on the oxidative burst of neutrophils. The data also suggest that, during these reactions, the influence of a fraction of flavonoids and their polyphenolic derivatives on cellular functions may change. On the whole, the results of the study provide a better understanding of the effects of polyphenols on human health. In addition, these results reveal the structure-activity relationship of these polyphenols and may be useful in a search for new therapeutic agents against diseases associated with oxidative stress.

Differences in the Formation of Reactive Oxygen Species and Their Cytotoxicity between Thiols Combined with Aqua- and Cyanocobalamins.

Cobalamin is an essential nutrient required for the normal functioning of cells. Its deficiency can lead to various pathological states. Hydroxocobalamin (HOCbl) and cyanocobalamin (CNCbl) are the forms of vitamin B12 that are most commonly used for supplementation. There is substantial evidence indicating that cobalamins can both suppress and promote oxidative stress; however, the mechanisms underlying these effects are poorly understood. Here, it was shown that the oxidation of thiols catalyzed by HOCbl and CNCbl is accompanied by reactive oxygen species (ROS) production and induces, under certain conditions, oxidative stress and cell death. The form of vitamin B12 and the structure of thiol play a decisive role in these processes. It was found that the mechanisms and kinetics of thiol oxidation catalyzed by HOCbl and CNCbl differ substantially. HOCbl increased the rate of oxidation of thiols to a greater extent than CNCbl, but quenched ROS in combination with certain thiols. Oxidation catalyzed by CNCbl was generally slower. Yet, the absence of ROS quenching resulted in their higher accumulation. The aforementioned results might explain a more pronounced cytotoxicity induced by combinations of thiols with CNCbl. On the whole, the data obtained provide a new insight into the redox processes in which cobalamins are involved. Our results might also be helpful in developing new approaches to the treatment of some cobalamin-responsive disorders in which oxidative stress is an important component.

Antioxidant and iron-chelating properties of taxifolin and its condensation product with glyoxylic acid.

The condensation of taxifolin with glyoxylic acid was examined, and the properties of the resulting product were compared with those of taxifolin. The structure of the product was determined by NMR spectroscopy. The ability of the polyphenols to scavenge reactive oxygen species (ROS) was estimated by luminol-dependent chemiluminescence. The iron-chelating and iron-reducing activities were studied using absorption spectrophotometry. It was shown that the condensation leads to the formation of a dimer consisting of two taxifolin units linked through a carboxymethine bridge at the C-6 and C-8 positions of the A ring. The dimer exhibited a somewhat higher ROS scavenging activity than taxifolin. The iron-binding capacity of the compounds was proportional to the number of polyphenol units. The iron-reducing ability of the dimer was lower than that of taxifolin. Thus, the dimer possessed a higher antioxidant activity than the parent flavonoid. The data obtained may be useful for a better understanding of processes occurring in foods and beverages and in a search for new active compounds.

Comparison of Antioxidant Properties of a Conjugate of Taxifolin with Glyoxylic Acid and Selected Flavonoids.

It is known that flavonoids can react with toxic carbonyl compounds in the process of the storage, aging, and digestion of flavonoid-rich foods and beverages. However, the effect of these reactions on the antioxidant properties of the polyphenolic fraction and the properties of the resulting products remain poorly studied. The aim of the present work was to study the antioxidant activity of quercetin, taxifolin, catechin, eriodictyol, hesperetin, naringenin and a product of the condensation of taxifolin with glyoxylic acid, as well as to reveal the structure-activity relationship of these polyphenols. It was found that flavonoids containing the catechol moiety exhibited higher antioxidant activity than hesperetin and naringenin. The product showed the highest hydrogen peroxide scavenging activity, a lower metal-reducing and a higher iron-binding ability than catechol-containing flavonoids, and a lipid peroxidation inhibitory activity comparable with that of taxifolin. Thus, the condensation of flavonoids with toxic carbonyl compounds might lead to the formation of products exhibiting high antioxidant activity. Meanwhile, the conditions under which parent flavonoids and their products exhibit the maximal antioxidant activity may differ. The data suggest that the antioxidant profile of the polyphenolic fraction and bioavailability of polyphenols, carbonyl compounds, and metal ions may change when these reactions occur.

Sulfur-containing compounds quench 3,7-dihydro-2-methyl-6-(4-methoxyphenyl)imidazol[1,2-a]pyrazine-3-one chemiluminescence: Discrimination between true antioxidants and quenchers using xanthine oxidase.

The probe 3,7-dihydro-2-methyl-6-(4-methoxyphenyl)imidazol[1,2-a]pyrazine-3-one (MCLA) is widely used for studying the superoxide anion production and the efficiency of antioxidants in biological systems. Here we report that a number of sulfur-containing compounds applied in biochemical and cytological studies are able to suppress MCLA-derived chemiluminescence (MDCL) independent of their capability to scavenge superoxide anion. The most effective MDCL quenchers appeared to be the substances with thiocarbamoyl and thiocarbonyl groups coupled to cyclic molecules and several thiol- and disulfide-containing compounds. The analysis of MDCL kinetics in a xanthine oxidase system allows one to rapidly discriminate between true antioxidants and the quenchers of chemiluminescence.

Conductive vancomycin-loaded mesoporous silica polypyrrole-based scaffolds for bone regeneration.

Bone tissue engineering is considered an alternative approach for conventional strategies available to treat bone defects. In this study, we have developed bone scaffolds composed of hydroxyapaptite (HAp), gelatin and mesoporous silica, all recognized as promising materials in bone tissue engineering due to favorable biocompatibility, osteoconductivity and drug delivery potential, respectively. These materials were coupled with conductive polypyrrole (PPy) polymer to create a novel bone scaffold for regenerative medicine. Conductive and non-conductive scaffolds were made by slurry casting method and loaded with a model antibiotic, vancomycin (VCM). Their properties were compared in different experiments in which scaffolds containing PPy showed good mechanical properties, higher protein adsorption and higher percentage of VCM release over a long duration of time compared to non-conductive scaffolds. Osteoblast cells were perfectly immersed into the gelatin matrix and remained viable for 14 days. Overall, new conductive composite bone scaffolds were created and the obtained results strongly verified the applicability of this conductive scaffold in drug delivery, encouraging its further development in tissue engineering applications.