Mechanisms of regulation of compensatory platelet response in nephrolithiasis-associated hematuria in women with the follicular phase of the cycle

Barinov E.F., Akhundova S.A.

Donetsk State Medical University named after M. Gorky, Donetsk, Russia

Objective. Evaluation of the severity of hematuria, the blood estradiol (Es) and progesterone (Pr) levels, the functional activity of platelet receptors and determination of the features of regulation of the platelet component of hemostasis in women with the follicular phase (FF) of the cycle.
Material and methods. The study included 59 women of reproductive age with nephrolithiasis, in whom hematuria was detected during examination. The blood Es and Pr levels were studied on the UniCel DxI 800 analyzer. The activity of purine P2Y- and PX1-receptors, TR-receptor, α2-adrenoreceptor, GPVI-receptor, PAF-receptor and adenosine A2A-receptor was analyzed. Receptor agonists were used in concentrations of EC50 and EC10. Platelet aggregation was assessed by the turbidimetric method on the ChronoLog analyzer. Statistical analysis was performed using the MedCalc package.
Results. In the examined contingent of women, the Es level was in the range of 164,3±5,0 pg/ml, and Pr – 0,44±0,04 ng/ml. The analysis of the platelet receptor apparatus revealed hyperreactivity of the PAF receptor and P2X1 receptor, normoreactivity of the purine P2Y receptors, A2A receptor and TR receptor, hyporeactivity of the GPVI receptor and α2-adrenoreceptor. The revealed dependence of hematuria on the Es level was associated with negative modulation of the signaling of the P2Y receptors, α2-adrenoreceptor and TR receptor. The compensatory platelet response was achieved due to the synergism of the P2Y receptors, P2X1 receptor and PAF receptor. The maximum effect of aggregation in vitro was reproduced during the interaction of purine P2Y receptors and P2X1 receptor, which was associated with an increase in the intracellular Ca2+ level
of as a result of co-activation of signaling through Gq and Gi proteins and the opening of the ATP-dependent cation channel.
Conclusion. Understanding the mechanisms of modulation of compensatory platelet response in women with follicular phase of the cycle is necessary for the development of a strategy for personalized diagnostics and treatment of complications of nephrolithiasis.

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About the Authors

Eduard F. Barinov – Dr.Sci. (Med.), Professor, Head of the Department of Histology, Cytology, Embryology and Molecular Medicine, Donetsk State Medical University named after M. Gorky. Address: 16 Ilyicha Avenue, Donetsk, 84003; tel.: +7 (949) 327-68-66; e-mail: barinov.ef.@gmail.com. ORCID: https://orcid.org/0000-0002-8070-2242
Sabina A. Akhundova – Senior Lecturer, Department of Histology, Cytology, Embryology and Molecular Medicine, Donetsk State Medical University named after M. Gorky. Address: 16 Ilyicha Avenue, Donetsk, 84003; tel.: +7 (949) 384-92-07; e-mail: barkova.sabina@bk.ru. ORCID: https://orcid.org/0009-0001-8400-6500

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