Влияние Прогестерона На Функциональную Активность Гликопротеина-P В Эксперименте

Shchulkin, A. V.; Chernykh, I. V.; Yakusheva, E. N.; Popova, N M; Мыльников, Павел Юрьевич

doi:10.30906/0023-1134-2018-52-7-3-8

Cited by 2 publications

(2 citation statements)

References 11 publications

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“…Активность Рgp способна значительно изменяться под влиянием внешних и внутренних факторов, в том числе под действием гормонов [3][4][5]. Известно, что в течение беременности в организме наблюдается выраженная гормональная перестройка, сопровождающаяся нарастанием сывороточных концентраций половых гормонов [6], что предполагает изменение функционирования Рgp в организме беременной.…”

Section: функциональная активность гликопротеина-р у кроликов породы unclassified

“…В исследовании на кроликах нами было установлено, что введение прогестерона в дозе 2 мг/кролик при овариоэктомии приводило к повышению функциональной активности Pgp по сравнению с показателями животных, подвергнутых изолированной овариоэктомии, однако активность транспортера оставалась сниженной по сравнению с данными до операции. Применение прогестерона в дозе 15 мг/кролик на фоне овариоэктомии повышало функциональную активность Pgp по сравнению с результатами кастрированных кроликов, восстанавливая его активность до показателей интактных животных [5]. Индуцирующее влияние прогестерона на белок-транспортер в данном эксперименте обусловлено его низкими сывороточными концентрациями.…”

Section: функциональная активность гликопротеина-р у кроликов породы unclassified

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P-glycoprotein functional activity in «soviet chinchilla» rabbits during pregnancy

Popova

Михайловна²,

Shchulkin

et al. 2018

I.P. Pavlov Russian Medical Biological Herald

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P-glycoprotein (Pgp, ABCB1-protein) is a membrane transporter protein that plays the key role in pharmacokinetics of drugs with a broad spectrum of action. Substrates of this transporter are some medical drugs (antibacterial, antiretroviral, hypotensive) that are prescribed to pregnant women for long-term intake, sometimes throughout the whole gestation period. Aim to study the activity of Pgp on the organism level in rabbits of Soviet Chinchilla breed in pregnancy. Materials and Methods. The study was performed on 21 Soviet Chinchilla female rabbits (3000-3500 g). The animals were divided into 3 series. The first series (n=6) included rabbits with 7 days of pregnancy; the second series (n=5) - animals with 14 days of pregnancy; the third series (n=10) - rabbits with 21 days of pregnancy. 7 Days before the study and in the indicated gestation periods, functional activity of Pgp was assessed by the pharmacokinetics of marker transporter substrate – fexofenadine, after its single oral introduction (67.5 mg/kg). Besides, serum concentrations of progesterone, estradiol, testosterone and prolactin were determined by radio immune method Results. In all the studied gestational periods, serum concentrations of estradiol, testosterone and prolactin did not significantly differ from those before pregnancy, but the level of progesterone in blood serum was significantly elevated above the norm. On the 7th day of pregnancy pharmacokinetic parameters of fexofenadine did not show any reliable changes as compared to the initial va-lues. On the 14th day of pregnancy a reliable increase in Cmax, AUC0-t, T1/2 of fexofenadine was noted as compared to the parameters before pregnancy, which indicates a decrease in Pgp functional activity on the organism level. On the 21st day of pregnancy Cmax of fexofenadine remained elevated. Other pharmacokinetic parameters of fexofenadine did not show reliable changes. Conclusion. Reduction in Pgp functional activity, determined by the pharmacokinetics of its marker substrate (fexofenadine), was noted in rabbits of Soviet Chinchilla breed on the 14th and 21st days of pregnancy with the underlying significant increase in progesterone level.

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Section: функциональная активность гликопротеина-р у кроликов породы unclassified

P-glycoprotein functional activity in «soviet chinchilla» rabbits during pregnancy

Popova

Михайловна²,

Shchulkin

et al. 2018

I.P. Pavlov Russian Medical Biological Herald

View full text Add to dashboard Cite

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A study of influence of progesterone on activity of Glycoprotein-P in vitro

Erokhina

Abalenikhina

Shchulkin

et al. 2020

I.P. Pavlov Russian Medical Biological Herald

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Background. Glycoprotein-P (Pgp, АВСВ1) is a transporter protein participating in pharmacokinetics of medical drugs, and also in development of resistance of tumor cells to chemotherapy. Aim. To study the influence of progesterone on the activity of Pgp in vitro on a cell model of human small intestinal epithelium. Materials and Methods. The work was conducted on Caco-2 cells. The activity of Pgp was evaluated by transport of fexofenadine in a special transwell-system. Concentration of fexofenadine was analyzed by HPLC method. The amount of Pgp was determined by EIA method. Four series of experiments were conducted: control cells preincubated with clean transport medium without addition of any substances; influence of rifampicin on the activity and synthesis of Pgp in the concentration 10 mol/l in preincubation for 3 days (induction control); influence of progesterone on the activity of Pgp in concentrations 1, 10 and 100 mol/l in preincubation for 30 min; influence of progesterone on the activity and synthesis of Pgp in concentrations 1, 10 and 100 mol/l in preincubation for 3 days. Results. Progesterone in the concentrations 1 and 10 M in incubation with cells within 30 minutes did not show any reliable influence on the activity of Pgp, however, in concentration 100 M it reduced the activity of the transporter protein. In incubation of Caco-2 cells with progesterone in concentrations 1, 10 and 100 M within 3 days the activity of Pgp remained unchanged. Progesterone in concentration 100 M in incubation within 3 days significantly increased synthesis of Pgp in enterocytes by 114.3% as compared to control, and in other used concentrations (1 and 10 M) it produced no reliable effect. Conclusion. In in vitro experiments on Caco-2 cells progesterone in concentration 100 M produces a direct inhibiting effect on the activity of Pgp; however, in incubation within 3 days it increases synthesis of the transporter protein, which cancels out its inhibitory activity.

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Влияние Прогестерона На Функциональную Активность Гликопротеина-P В Эксперименте

Cited by 2 publications

References 11 publications

P-glycoprotein functional activity in «soviet chinchilla» rabbits during pregnancy

P-glycoprotein functional activity in «soviet chinchilla» rabbits during pregnancy

A study of influence of progesterone on activity of Glycoprotein-P in vitro

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