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In vitro gender-dependent inhibition of porcine cytochrome p450 activity by selected flavonoids and phenolic acids.

Ekstrand B, Rasmussen MK, Woll F, Zlabek V, Zamaratskaia G - Biomed Res Int (2015)

Bottom Line: Additionally, isorhamnetin competitively inhibited CYP3A in both genders.Neither phenolic acids nor rutin affected CYP450 activities.Taken together, our results suggest that the flavonoids myricetin, isorhamnetin, and quercetin may affect the activities of porcine CYP1A, CYP3A, and CYP2E1 in a gender-dependent manner.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science, Aarhus University, 8830 Tjele, Denmark.

ABSTRACT
We investigated gender-related differences in the ability of selected flavonoids and phenolic compounds to modify porcine hepatic CYP450-dependent activity. Using pools of microsomes from male and female pigs, the inhibition of the CYP families 1A, 2A, 2E1, and 3A was determined. The specific CYP activities were measured in the presence of the following selected compounds: rutin, myricetin, quercetin, isorhamnetin, p-coumaric acid, gallic acid, and caffeic acid. We determined that myricetin and isorhamnetin competitively inhibited porcine CYP1A activity in the microsomes from both male and female pigs but did not affect the CYP2A and CYP2E1. Additionally, isorhamnetin competitively inhibited CYP3A in both genders. Noncompetitive inhibition of CYP3A activity by myricetin was observed only in the microsomes from male pigs, whereas CYP3A in female pigs was not affected. Quercetin competitively inhibited CYP2E1 and CYP1A activity in the microsomes from male pigs and irreversibly CY3A in female pigs. No effect of quercetin on CYP2E1 was observed in the microsomes from female pigs. Neither phenolic acids nor rutin affected CYP450 activities. Taken together, our results suggest that the flavonoids myricetin, isorhamnetin, and quercetin may affect the activities of porcine CYP1A, CYP3A, and CYP2E1 in a gender-dependent manner.

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In vitro inhibition of CYP2E1 by quercetin in hepatic microsomes from male and female pigs. Data are presented as the mean percentage of remaining activity and standard error of the enzyme activity for three pools with microsomes from 2 male pigs in each pool and two pools with microsomes from 2 female pigs in each pool. (a) Effect of quercetin with (grey bars) and without (white bars) 15 min preincubation. (b) Saturation curve for p-nitrophenol hydroxylation (CYP2E1) in hepatic microsomes from male pigs in the presence of quercetin.
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fig4: In vitro inhibition of CYP2E1 by quercetin in hepatic microsomes from male and female pigs. Data are presented as the mean percentage of remaining activity and standard error of the enzyme activity for three pools with microsomes from 2 male pigs in each pool and two pools with microsomes from 2 female pigs in each pool. (a) Effect of quercetin with (grey bars) and without (white bars) 15 min preincubation. (b) Saturation curve for p-nitrophenol hydroxylation (CYP2E1) in hepatic microsomes from male pigs in the presence of quercetin.

Mentions: Among the tested compounds, quercetin inhibited CYP2E1 activity (remaining activity varied from 65.1 to 66.9%). This inhibition was observed only in the microsomes from male pigs (Figure 1(d)) and was not affected by preincubation step indicating reversible inhibition (Figure 4(a)). Analysis of the inhibition mode indicated noncompetitive inhibition of CYP2E1 activity (Figure 4(b)).


In vitro gender-dependent inhibition of porcine cytochrome p450 activity by selected flavonoids and phenolic acids.

Ekstrand B, Rasmussen MK, Woll F, Zlabek V, Zamaratskaia G - Biomed Res Int (2015)

In vitro inhibition of CYP2E1 by quercetin in hepatic microsomes from male and female pigs. Data are presented as the mean percentage of remaining activity and standard error of the enzyme activity for three pools with microsomes from 2 male pigs in each pool and two pools with microsomes from 2 female pigs in each pool. (a) Effect of quercetin with (grey bars) and without (white bars) 15 min preincubation. (b) Saturation curve for p-nitrophenol hydroxylation (CYP2E1) in hepatic microsomes from male pigs in the presence of quercetin.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317639&req=5

fig4: In vitro inhibition of CYP2E1 by quercetin in hepatic microsomes from male and female pigs. Data are presented as the mean percentage of remaining activity and standard error of the enzyme activity for three pools with microsomes from 2 male pigs in each pool and two pools with microsomes from 2 female pigs in each pool. (a) Effect of quercetin with (grey bars) and without (white bars) 15 min preincubation. (b) Saturation curve for p-nitrophenol hydroxylation (CYP2E1) in hepatic microsomes from male pigs in the presence of quercetin.
Mentions: Among the tested compounds, quercetin inhibited CYP2E1 activity (remaining activity varied from 65.1 to 66.9%). This inhibition was observed only in the microsomes from male pigs (Figure 1(d)) and was not affected by preincubation step indicating reversible inhibition (Figure 4(a)). Analysis of the inhibition mode indicated noncompetitive inhibition of CYP2E1 activity (Figure 4(b)).

Bottom Line: Additionally, isorhamnetin competitively inhibited CYP3A in both genders.Neither phenolic acids nor rutin affected CYP450 activities.Taken together, our results suggest that the flavonoids myricetin, isorhamnetin, and quercetin may affect the activities of porcine CYP1A, CYP3A, and CYP2E1 in a gender-dependent manner.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science, Aarhus University, 8830 Tjele, Denmark.

ABSTRACT
We investigated gender-related differences in the ability of selected flavonoids and phenolic compounds to modify porcine hepatic CYP450-dependent activity. Using pools of microsomes from male and female pigs, the inhibition of the CYP families 1A, 2A, 2E1, and 3A was determined. The specific CYP activities were measured in the presence of the following selected compounds: rutin, myricetin, quercetin, isorhamnetin, p-coumaric acid, gallic acid, and caffeic acid. We determined that myricetin and isorhamnetin competitively inhibited porcine CYP1A activity in the microsomes from both male and female pigs but did not affect the CYP2A and CYP2E1. Additionally, isorhamnetin competitively inhibited CYP3A in both genders. Noncompetitive inhibition of CYP3A activity by myricetin was observed only in the microsomes from male pigs, whereas CYP3A in female pigs was not affected. Quercetin competitively inhibited CYP2E1 and CYP1A activity in the microsomes from male pigs and irreversibly CY3A in female pigs. No effect of quercetin on CYP2E1 was observed in the microsomes from female pigs. Neither phenolic acids nor rutin affected CYP450 activities. Taken together, our results suggest that the flavonoids myricetin, isorhamnetin, and quercetin may affect the activities of porcine CYP1A, CYP3A, and CYP2E1 in a gender-dependent manner.

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