Effects of non-steroidal anti-inflammatory agents on systemic hemostasis during the most acute period of cold injury in rats

Authors

DOI:

https://doi.org/10.15587/2519-4852.2023.294311

Keywords:

acute general cooling, diclofenac sodium, etoricoxib, blood coagulation, experiment

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) have recently been considered promising agents for the prevention and treatment of cold injuries. The results of previous studies demonstrate a distinct frigoprotective effect of diclofenac sodium and etoricoxib.

The aim of the study: to assess the impact of diclofenac sodium and etoricoxib, as the most effective frigoprotectors among NSAIDs, on coagulation indicators during the most acute phase of cold injuries using an acute model of general cooling in rats.

Materials and Methods: The experiment was carried out using 41 outbreed male rats weighing 310±10 g. Cold injury was induced by acute general cooling (exposure to –18 °C for 2 hours). Diclofenac sodium (7 mg/kg) and etoricoxib (5 mg/kg) were administered intragastrically 30 minutes before the onset of cold exposure. Rectal temperature was measured before and after cold exposure. Immediately after exposure, plasma was used to determine prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen levels, and in blood serum – the residual amount of prothrombin, thrombin, fibrinogen, as well as D-dimer using species-specific immunoenzymatic analysis kits.

Results: Etoricoxib and especially diclofenac sodium significantly reduced the degree of hypothermia (rectal temperature decreased by 1.3 % and 1.9 %, respectively, compared to a 5.4 % decrease in the control group, p < 0.05). In the acute phase of cold injury in the untreated control group, there was a significant increase in D-dimer (by 2.7 times) and fibrinogen content (by 1.9 times) in blood serum, alongside a 21.7 % increase in thrombin time, indicating a heightened risk of thrombus formation and DIC syndrome development. The other coagulation indicators did not show significant changes. Both diclofenac sodium and etoricoxib significantly reduced elevated D-dimer and serum fibrinogen, normalizing thrombin time and indicating an antithrombotic effect. There was no significant difference in the effect of both NSAIDs on blood coagulation status.

Conclusions: The acute phase of cold injury demonstrates a dangerous shift in blood coagulation towards thrombus formation and DIC syndrome development. Prophylactic use of diclofenac sodium and, to a lesser extent, etoricoxib displays an anti-hypothermic effect, reducing the risk of thrombosis and DIC syndrome. This proves the expediency of using these NSAIDs for acute cold injury

Supporting Agency

  • “Experimental substantiation for improving the effectiveness of prevention and treatment of cold injuries” of the list of scientific studies of the Ministry of Health of Ukraine, carried out at the expense of the state budget of Ukraine No. 0120u102460 (Order of the Ministry of Health of Ukraine No. 2651 of 17.11.2020)

Author Biographies

Sergiy Shtrygol’, National University of Pharmacy

Doctor of Medical Sciences, Professor

Department of Pharmacology and Pharmacotherapy

Andrii Taran, National University of Pharmacy

PhD, Associate Professor

Department of Pharmacology and Pharmacotherapy

Tetiana Yudkevych, National University of Pharmacy

Deputy Director for Research

Educational and Scientific Institute of Applied Pharmacy

Dmytro Lytkin, National University of Pharmacy

PhD

Educational and Scientific Institute of Applied Pharmacy

Iryna Lebedinets, National University of Pharmacy

Specialist

Educational and Scientific Training Laboratory of Medical and Biological Sciences

Polina Chuykova, National University of Pharmacy

Posgraduate Student

Department of Pharmacology and Pharmacotherapy

Olga Koiro, National University of Pharmacy

PhD, Associate Professor

Department of Pharmacology and Pharmacotherapy

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Effects of non-steroidal anti-inflammatory agents on systemic hemostasis during the most acute period of cold injury in rats

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Published

2023-12-31

How to Cite

Shtrygol’, S., Taran, A., Yudkevych, T., Lytkin, D., Lebedinets, I., Chuykova, P., & Koiro, O. (2023). Effects of non-steroidal anti-inflammatory agents on systemic hemostasis during the most acute period of cold injury in rats. ScienceRise: Pharmaceutical Science, (6(46), 25–30. https://doi.org/10.15587/2519-4852.2023.294311

Issue

No. 6(46) (2023)

Section

Pharmaceutical Science

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Copyright (c) 2023 Sergiy Shtrygol’, Andrii Taran, Tetiana Yudkevych, Dmytro Lytkin, Iryna Lebedinets, Polina Chuykova, Olga Koiro

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