The frigoprotective effects of etoricoxib and diclofenac sodium in a model of acute general cooling in rats: the role of leukotrienes, interleukins, and nitric oxide synthase
DOI:
https://doi.org/10.15587/2519-4852.2026.359158Keywords:
frigoprotectors, acute general cooling, leukotrienes, interleukins, nitric oxide synthase, etoricoxib, diclofenac sodiumAbstract
The aim: The aim of the study was to evaluate the role of leukotrienes, interleukins, and nitric oxide synthase in frigoprotective effect of etoricoxib and diclofenac sodium in a model of acute general cooling in rats.
Material and methods: Acute general cooling was induced by exposing rats to −18 °C for 2 hours without animal mobility restriction. 30 min before cold exposure animals were treated with etoricoxib (5 mg/kg) or diclofenac sodium (7 mg/kg). Body temperature was measured before and after acute general cooling modeling. In rat liver the following parameters were determined: 5-lipoxygenase (5-LOX), leukotriene B4 (LTB4), total leukotrienes (LTs), interleukins (IL-1β, IL-4, IL-6, IL-10), tumor necrosis factor-α (TNF-α), and nitric oxide synthase (NOS).
Results: activation of the lipoxygenase pathway of arachidonic acid metabolism was characterized by a significant increase in leukotriene levels (total and leukotriene B4) without substantial changes in proinflammatory cytokines (IL-1β, IL-6, TNF-α) but with a significant decrease in anti-inflammatory cytokines (IL-4, IL-10) in the liver. Etoricoxib and diclofenac sodium similarly reduced the severity of hypothermia, prevented the increase in leukotriene levels without affecting 5-LOX content. Etoricoxib and particularly diclofenac sodium significantly reduced IL-1β levels without substantial changes in the other cytokines. Both studied medicines restored NOS levels to those observed in the intact control group.
Conclusions: obtained results experimentally substantiate the possibility of diclofenac sodium and etoricoxib to decrease the severity of acute general cooling, while also demonstrating certain differences in the mechanisms underlying their frigoprotective effects
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).
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Copyright (c) 2026 Sergiy Shtrygol’, Olesia Kudina, Dmytro Lytkin, Andrii Taran, Tetiana Yudkevych

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