The hepatic cytochrome p450 enzymes 1 A, 2A19 and 2E1 is very important for the elimination of skatole from the body of pigs. Impaired skatole metabolism, results in skatole accumulation, which give rise to off flavor of the meat. Several metabolites of skatole has been identified, however the role of these metabolites in the inhibition of the skatole metabolizing enzymes are not documented. Using microsomes from pigs and fish, we determined the ability of several skatole metabolites to inhibit CYP1 A, CYP2A19 and CYP2E1 dependent activity. Our results show that 2-aminoacetophenone is an inhibitor of porcine CYP2A19 and CYP2E1 activity, but not the piscine orthologues. In conclusion, there is species specific differences in the inhibition of CYP1 A and CYP2A19 dependent metabolism of probe substrates. This is relevant to the evaluation of different model systems and to the reduction of off flavor of meat.

• MeSH
• acetofenony toxicita   MeSH
• červené maso analýza   MeSH
• cytochrom P-450 CYP1A1 antagonisté a inhibitory   metabolismus   MeSH
• cytochrom P-450 CYP2E1 metabolismus   MeSH
• druhová specificita MeSH
• inhibitory cytochromu P450 CYP2E1 toxicita   MeSH
• jaterní mikrozomy účinky léků   metabolismus   MeSH
• játra účinky léků   metabolismus   MeSH
• kumariny toxicita   MeSH
• nitrofenoly toxicita   MeSH
• oxaziny toxicita   MeSH
• potrava z moře (živočišná) analýza   MeSH
• prasata MeSH
• ryby MeSH
• skatol toxicita   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

This is the first in vitro study to investigate gender-related differences in the regulation of human cytochrome P450 by the flavonoids. Activities of CYP2E1 and CYP3A were measured in the presence of quercetin, myricetin, or isorhamnetin in hepatic microsomal pools from male and female donors. Hydroxylation of p-nitrophenol (PNPH) was measured to determine CYP2E1 activity, and O-dealkylation of 7-benzyloxy-4-trifluoromethylcoumarin (BFC) was measured to determine CYP3A activity. Quercetin, but not myricetin or isorhamnetin, competitively inhibited PNPH activity in human recombinant cDNA-expressed CYP2E1 with the Ki=52.1±6.31μM. In the human microsomes, slight inhibition of PNPH activity by quercetin was not considered as physiologically relevant. Quercetin inhibited BFC activity in human recombinant cDNA-expressed CYP3A4 competitively with the Ki=15.4±1.52μM, and myricetin - noncompetitively with the Ki=74.6±7.99μM. The degree of inhibition by quercetin was similar between genders. Myricetin showed somewhat stronger inhibition in female pools, but the Ki values were higher than physiologically relevant concentrations. Isorhamnetin did not affect either PNPH or BFC activity. We concluded that observed inhibition of CYP2E1 and CYP3A by some flavonols were not gender-dependent.

• MeSH
• cytochrom P-450 CYP2E1 metabolismus   MeSH
• cytochrom P-450 CYP3A metabolismus   MeSH
• flavonoidy farmakologie   MeSH
• hydroxylace MeSH
• inhibitory cytochromu P450 CYP2E1 farmakologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• jaterní mikrozomy účinky léků   metabolismus   MeSH
• kumariny metabolismus   MeSH
• lidé MeSH
• nitrofenoly metabolismus   MeSH
• quercetin analogy a deriváty   farmakologie   MeSH
• sexuální faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH