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

The aim of the study was to analyse protective effects of different doses of pomiferin in therapy of reperfusion injury. Rats were randomly divided into five groups (n=10). One group was intact. Three medicated groups and one placebo group were subjected to ischaemia and reperfusion of the left kidney. Pomiferin was administrated by single gastric gavage in 2 ml of 0.5% Avicel solution in doses of 5, 10 and 20 mg/kg. The placebo group was given only Avicel solution. On day 15, all the animals were exsanguinated and the reperfused kidneys were recovered. Selected biochemical markers were assessed in blood: antioxidative enzymes, total antioxidative capacity, malondialdehyde, creatinine, urea and uric acid. Creatinine, urea and total proteins were analysed in urine and 24-hour diuresis was recorded. The kidney tissue samples were used for histopathological examination.The results confirmed the expected protective effects of pomiferin. Pomiferin supported defensive reactions of the body against free radicals (increased levels of superoxide dismutase, total antioxidative capacity), decreased lipid peroxidation (decreased malondialdehyde) and contributed to the recovery of kidney functions (creatinine and urea in blood). The best biochemical and histopathological results were achieved after pomiferin administration in the dose of 5 mg/kg.

• Klíčová slova
• antioxidative effect, ischaemia-reperfusion, kidney, pomiferin, therapy,
• Publikační typ
• časopisecké články MeSH