Keywords
acute heat injury
celecoxib
paracetamol
Selye’s triad
heat shock protein
interleukin-1β
interleukin-4
celecoxib
paracetamol
Selye’s triad
heat shock protein
interleukin-1β
interleukin-4
Abstract
Acute heat injury (AHI) is a critical pathological condition caused by excessive exposure of the body to high environmental temperatures, accompanied by homeostasis disruption and the development of a systemic stress response. Its primary manifestation is known as Selye’s triad: adrenal gland hypertrophy, thymus atrophy, and ulcerative lesions of the gastric mucosa. Molecular mediators of stress and inflammation, in particular heat shock proteins and cytokines, play a significant role in the pathogenesis of AHI. The search for effective pharmacological agents aimed at reducing systemic inflammation and the severity of the stress response remains relevant. Previous studies have shown that COX inhibitors such as celecoxib and paracetamol may serve as such agents.
The aim of the study was to assess the effects of paracetamol and celecoxib on systemic (Selye’s triad) and molecular (HSP70, IL-1β, IL-4) markers of the stress response in a rat model of AHI. The experiments were conducted on male white rats exposed to a temperature of + 55 °C for 30 min. Rectal temperature was measured before and after the heat exposure. Paracetamol at a dose of 125 mg/kg or celecoxib at a dose of 8.4 mg/kg was administered intragastrically 60 min before the exposure. Stress- response parameters were assessed based on Selye’s triad criteria (relative weights of the adrenal glands and thymus, frequency of ulceration), as well as the levels of HSP70, IL-1β, and IL-4 in blood serum and liver homogenates (measured by ELISA). Acute heat injury in rats was accompanied by hyperthermia, a significant increase in the levels of heat shock protein and interleukins in blood serum and liver, as well as systemic manifestations: a tendency toward reduced adrenal gland mass (a specific feature of the heat stress model), significant thymus mass loss, and mild ulcerative lesions in the gastric mucosa. Paracetamol and celecoxib demonstrated markedthermoprotective and stress-protective properties: they preserved normal adrenal and thymus mass indices, reduced the frequency of ulceration, and decreased the content of HSP70, IL-1β, and IL-4 in blood serum and liver. Celecoxib more effectively reduced inflammatory and stress markers compared to paracetamol and also prevented the development of mucosal hyperemia in the stomach. No statistically significant correlations were found between the degree of hyperthermia and the levels of studied markers in serum and liver, or between their serum and hepatic concentrations, highlighting the complex, multifactorial pathogenesis of hyperthermia in AHI. The only statistically significant direct correlation (r = 0.827, p < 0.05) was found between the severity of hyperthermia and the level of IL-4 in the liver under the influence of celecoxib. The results obtained provide experimental evidence for the advisability of using celecoxib in particular as a thermoprotective agent in acute heat injury.
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