Individual trombocity reactivity in hematuria associated with nephrolitiasis: the role of purinergic signalisation in the treatment of nesteroid protective preparations

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Abstract

Aim of the study was to establish the significance of TR-receptor, P2X1-receptor and P2Y-receptor synergism for the efficiency of TC aggregation in patients with different sensitivity to non-selective NSAIDs, which will allow us to approach an understanding the causes of the variability of hematuria associated with NLT.

Material and methods. The study was prospective and included 60 patients with nephrolithiasis who were treated with high doses of NSAIDs for analgesia. The cohort of patients was divided into two groups: with effective (group 1. n=30) and ineffective (group 2. n=30) COX inhibition. The severity of hematuria was assessed during 7 days of drug therapy. The activity of TR receptors, purine P2X1- and P2Y- receptors of platelets (Tc) was analysed by turbidimetric method on ChronoLog analyser (USA). Agonists (ATP, ADP and Arachidonic acid) were used at EC50 and EC10 concentrations.

Results. In the 1 group of patients, hyporeactivity of the TP receptor was established within 72 hours, which was restored to the level of normoreactivity on the 5th day of therapy. Optimal modulation of the compensatory reaction of Pl in response to hematuria was provided through the synergism of purine P2X1 and P2Y receptors. Optimal modulation of the compensatory reaction of Tc in response to hematuria was provided through the synergism of purine P2X1 and P2Y receptors. On the 7th day, a residual level of COX activity was reached, while intracellular signaling associated with stimulation of the TP receptor and purine P2 receptors did not provide the limitation of hematuria. In the 2 group, when patients were prescribed NSAIDs for 7 days, hyperreactivity of the TP receptor, P2 receptors and a stable level of microhematuria remained. In the case of COX resistance and increased production of TxA2, the maximum increase in proaggregant Tc activity was ensured through the stereotypical mechanism of intracellular signaling associated with stimulation of P2Y receptors (through Gi- and Gq- proteins) and the TP receptor (through Gq- and Gq12/13- proteins).

Conclusion. Further study of the mechanisms of crosstalk signaling pathways with different COX activity will allow us to establish promising directions for pharmacological correction aimed at preventing hematuria and ensuring hemostasis in nephrolithiasis.

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About the authors

Eduard F. Barinov

FSBEI HE Donetsk State Medical University

Author for correspondence.
Email: barinov.ef@gmail.com
ORCID iD: 0000-0002-8070-2242

Head of the department the Histology, Cytology and Embryology FSBEI HE «Donetsk State Medical University». Doctor of medical sciences, Professor

Russian Federation, Ilyich Av, 16, DPR, Donetsk, 84003

Alina S. Yureva

FSBEI HE Donetsk State Medical University

Email: Alina777Y@yandex.ru
ORCID iD: 0009-0008-3926-4042

assistant of the department the Histology, Cytology and Embryology, FSFEI HE «Donetsk State Medical University»

Russian Federation, Ilyich Av, 16, DPR, Donetsk, 84003

Sabina Akber kyzy Akhundova

FSBEI HE Donetsk State Medical University

Email: barkova.sabina@bk.ru
ORCID iD: 0009-0001-8400-6500

assistant of the department the Histology, Cytology and Embryology, FSFEI HE «Donetsk State Medical University»

Russian Federation, Ilyich Av, 16, DPR, Donetsk, 84003

Dina I. Giller

FSBEI HE Donetsk State Medical University

Email: dina7670@mail.ru
ORCID iD: 0000-0002-0279-1294

assistant of the department the Histology, Cytology and Embryology, FSFEI HE «Donetsk State Medical University»

Russian Federation, Ilyich Av, 16, DPR, Donetsk, 84003

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