Flavonoids are common plant natural products able to suppress ROS-related damage and alleviate oxidative stress. One of key mechanisms, involved in this phenomenon is chelation of transition metal ions. From a physiological perspective, iron is the most significant transition metal, because of its abundance in living organisms and ubiquitous involvement in redox processes. The chemical, pharmaceutical, and biological properties of flavonoids can be significantly affected by their interaction with transition metal ions, mainly iron. In this review, we explain the interaction of various flavonoid structures with Fe(II) and Fe(III) ions and critically discuss the influence of chelated ions on the flavonoid biochemical properties. In addition, specific biological effects of their iron metallocomplexes, such as the inhibition of iron-containing enzymes, have been included in this review.

• Klíčová slova
• flavonoids, iron ions, metallocomplexes,
• MeSH
• antioxidancia chemie   farmakologie   MeSH
• chelátory chemie   farmakologie   MeSH
• flavonoidy chemie   MeSH
• hem chemie   MeSH
• ionty chemie   metabolismus   MeSH
• komplexní sloučeniny chemie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• vazba proteinů MeSH
• vztahy mezi strukturou a aktivitou MeSH
• železo chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antioxidancia MeSH
• chelátory MeSH
• flavonoidy MeSH
• hem MeSH
• ionty MeSH
• komplexní sloučeniny MeSH
• železo MeSH

Quercetin is an abundant flavonoid in nature and is used in several dietary supplements. Although quercetin is extensively metabolized by human enzymes and the colonic microflora, we have only few data regarding the pharmacokinetic interactions of its metabolites. Therefore, we investigated the interaction of human and microbial metabolites of quercetin with the xanthine oxidase enzyme. Inhibitory effects of five conjugates and 23 microbial metabolites were examined with 6-mercaptopurine and xanthine substrates (both at 5 μM), employing allopurinol as a positive control. Quercetin-3'-sulfate, isorhamnetin, tamarixetin, and pyrogallol proved to be strong inhibitors of xanthine oxidase. Sulfate and methyl conjugates were similarly strong inhibitors of both 6-mercaptopurine and xanthine oxidations (IC50 = 0.2-0.7 μM); however, pyrogallol inhibited xanthine oxidation (IC50 = 1.8 μM) with higher potency vs. 6-MP oxidation (IC50 = 10.1 μM). Sulfate and methyl conjugates were approximately ten-fold stronger inhibitors (IC50 = 0.2-0.6 μM) of 6-mercaptopurine oxidation than allopurinol (IC50 = 7.0 μM), and induced more potent inhibition compared to quercetin (IC50 = 1.4 μM). These observations highlight that some quercetin metabolites can exert similar or even a stronger inhibitory effect on xanthine oxidase than the parent compound, which may lead to the development of quercetin-drug interactions (e.g., with 6-mercaptopurin or azathioprine).

• Klíčová slova
• 6-mercaptopurine, enzyme inhibition, pharmacokinetic interactions, quercetin metabolites, xanthine, xanthine oxidase,
• MeSH
• alopurinol chemie   farmakologie   MeSH
• inhibitory enzymů chemie   metabolismus   farmakologie   MeSH
• katalýza MeSH
• lidé MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• oxidace-redukce MeSH
• quercetin analogy a deriváty   chemie   metabolismus   farmakologie   MeSH
• vazba proteinů MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• xanthin chemie   farmakologie   MeSH
• xanthinoxidasa antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alopurinol MeSH
• inhibitory enzymů MeSH
• quercetin MeSH
• xanthin MeSH
• xanthinoxidasa MeSH

OBJECTIVES: Rutin, quercetin-3-O-rutinoside, a natural flavonol glycoside, has shown various in vitro benefits with potential use treating human diseases, especially cardiovascular system disorders. Antioxidant properties are assumed to underlie the majority of these benefits. Yet rutin pro-oxidant properties have been reported as well. Our research group has recently shown aggravating effects on isoprenaline (ISO)-induced cardiotoxicity in Wistar:Han rats after 24 hours. METHODS: This study was designed to examine in more detail the reasons for the negative effects of rutin (11.5 and 46 mg/kg, i.v.) after administration of ISO (100 mg/kg, s.c.) in rats within 2 hours of continuous experiment and in the H9c2 cardiomyoblast-derived cell line. RESULTS: Like our previous findings, rutin did not (11.5 or 46 mg/kg, i.v.) reduce the ISO-induced mortality within 2 hours although the lower dose significantly reduced cardiac troponin T (cTnT) and partly improved the histological findings. In contrast, the higher dose increased the mortality in comparison with solvent (1.26% w/v sodium bicarbonate). This was not caused by any specific haemodynamic disturbances. It appears to be associated with oxidative stress as rutin enhanced intracellular reactive oxygen species formation in vitro and had the tendency to increase it in vivo. CONCLUSIONS: Rutin, likely due to its pro-oxidative effects, can exacerbate catecholamine cardiotoxicity depending on the dose used.

• Klíčová slova
• Catecholamine, Flavonoid, H9c2 cell line, Isoprenaline, Reactive oxygen species, Rutin, Wistar rat,
• MeSH
• buněčné linie MeSH
• dinoprost analogy a deriváty   krev   MeSH
• elektrokardiografie MeSH
• glutathion krev   MeSH
• injekce intravenózní MeSH
• isoprenalin škodlivé účinky   MeSH
• Kaplanův-Meierův odhad MeSH
• kardiotoxicita etiologie   mortalita   MeSH
• myokard patologie   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• rutin aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• srdce účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 8-epi-prostaglandin F2alpha MeSH Prohlížeč
• dinoprost MeSH
• glutathion MeSH
• isoprenalin MeSH
• reaktivní formy kyslíku MeSH
• rutin MeSH