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The Ability of Gynipral to Modify Dydrogesterone’s Non-Genomic Effects on the Free-Radical Activity of Neutrophils in Women at Different Stages of Reproduction. P. 31–41

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Section: Physiology

UDC

612.112.9.91

Authors

Inna G. Paturova*, Tat’yana V. Polezhaeva**, Andrey N. Khudyakov **, Ol’ga N. Solomina**, Oksana M. Bezmel’tseva**, Ol’ga A. Bratukhina***, Viktor I. Tsirkin****/*****
*Kirov State Medical University (Kirov, Russian Federation)
**Institute of Physiology, Komi Science Centre, Ural Branch of the Russian Academy of Sciences (Syktyvkar, Russian Federation)
***Kirov Regional Clinical Perinatal Centre (Kirov, Russian Federation) ****Kazan State Medical University (Kazan, Russian Federation)
*****Vyatka State University (Kirov, Russian Federation)
Corresponding author: Inna Paturova, address: ul. K. Marksa 112, Kirov, 610020, Russian Federation; e-mail: paturova_ig@mail.ru

Abstract

The paper studies a 30-minute effect (at 37 °С) of peripheral blood preincubation with dydrogesterone (5·10–5 g/l) in women on the free-radical activity of neutrophils (in particular, on the activation of their membrane NADPH oxidase), which was determined using the Biochemiluminometer BChL-07 for the following 30 minutes (at 37 °C) in the presence of latex (0.08 μm in diameter) and luminol. We have shown that under these conditions, dydrogesterone, judging by the changes in the light sum (S, mV/s), maximum intensity of chemiluminescence (Imax, mV) and the time of reaching Imax (T, s), increases the free-radical activity of neutrophils in pregnant women (1st and 2nd trimesters) and parturient women (1st stage of labour), without exerting such an influence on neutrophils in the 3rd trimester of pregnancy and women with threatened preterm labour (2nd and 3rd trimesters). Addition of gynipral beta2-adrenergic receptor agonist (10–6 g/l) to the mixture placed in the biochemiluminometer for 30 minutes changed the non-genomic effect of dydrogesterone. In particular, during the 1st trimester of pregnancy gynipral blocked the ability of dydrogesterone to increase the free-radical activity of neutrophils; in the 2nd trimester and in labour it produced no effect on this ability; during the 3rd trimester gynipral even enhanced it, while at threatened preterm labour it did not restore the ability. This means that in the 1st trimester of pregnancy, neutrophils contain beta2-adrenergic receptors, whose activation blocks the non-genomic effect of dydrogesterone and thereby reduces the free-radical activity of neutrophils, enhanced by progesterone, thereby promoting the development of maternal immune tolerance to fetal antigens. During the 2nd and 3rd trimesters of pregnancy, as well as in labour, the effectiveness of beta2-adrenergic receptor activation is reduced. This is explained by the switching of beta2-adrenergic receptor coupling (from the Gs class of G-protein to the Gi) or by an increase in the expression of alpha-adrenergic receptors. In general, this situation contributes to increased (including due to the non-genomic effect of progesterone) free-radical activity of neutrophils, the need for which is constantly growing, especially just before and during labour.

Keywords

pregnancy, labour, threatened preterm labour, free-radical activity of neutrophils, dydrogesterone, gynipral
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