Catechins and other flavonoids as protectors against undesired modifications of biomolecules

Abstract

Undesired modifications of biomolecules (proteins, lipids and nucleic acids), mainly oxidation by reactive oxygen species, underlay many diseases and apparently aging. Compounds counteracting these modifications can therefore be candidates for potential drugs and aging-modifying agents. Naturally occurring compounds are especially interesting in this respect since knowledge of their properties may be a basis for dietary recommendations and functional food production. The aim of our studies was to compare the antioxidant properties and efficiency of a range of flavonoids and other natural antioxidants in protection against protein modifications and lipid peroxidation. We compared the ABTS*-scavenging activity capacity of a range of flavonoids and selected other antioxidants, their iron binding capacity estimated by the ferrozine competition test and strong iron binding evaluated by a modified deoxyribose degradation test, their potency to prevent peroxynitrite reactions in three different test systems, based on fluorescein bleaching, tyrosine nitration and serum albumin thiol oxidation as well as oxidation of dihydrorhodamine and fluorescein, and protein tyrosine chlorination by hypochlorous acid. The sequence of protective capacity of the antioxidants was different in various systems. Correlation analysis revealed that the hydroxyl group at the R04 position of the flavonoids contributes significantly to prevention of fluorescein bleaching, R3-OH is important for prevention of thiol oxidation while R5-OH and R03-OH are significant in prevention of tyrosine nitration. The total number of hydroxyl groups correlated with the ability of flavonoids to prevent oxidation reactions and the presence of vicinal hydroxyl groups correlated with flavonoid reactivity in all systems used [1]. Flavonoids were also active in preventing nitration of intracellular proteins. Flavonoids and other antioxidants were also compared as protective agents against glycation of serum albumin induced by various sugars (glucose, fructose and ribose) [2] and reactive aldehydes (glyoxal and methylglyoxal) [3] and blood plasma lipoproteins against lipid peroxidation induced by various agents (AAPH, peroxynitrite and hypochlorous acids). Catechins showed the highest ABTS*-scavenging capacity, the highest stoichiometry of Fe3+ reduction in the FRAP assay and belonged to the most efficient compounds in protection SIN-1 induced oxidation of dihydrorhodamine 123, AAPH-induced fluorescein bleaching and hypochlorite-induced fluorescein bleaching. (+)-Catechin and (-)-epicatechin were the most effective compounds in protection against AAPH-induced erythrocyte hemolysis while (-)-epicatechin gallate, (-)-epigallocatechin gallate and (-)-epigallocatechin protected at lowest concentrations against hypochlorite-induced hemolysis. The results demonstrate high potency of flavonoids in protection against undesired modifications of biomolecules, even at micromolar concentrations.