Comparative analysis of the effect of diclofenac sodium and etoricoxib on energy metabolism in rat liver in the acute general cooling model

Abstract

When the ambient temperature decreases, physiological mechanisms that prevent heat loss are activated. However, under cold stress hypothermia develops, which significantly disrupts the functioning of the body and can be transformed into life-threatening. Preventive use of nonsteroidal anti-inflammatory drugs, especially diclofenac sodium and etoricoxib, has been found to reduce the severity of cold trauma. Given that their frigoprotective effect can accompany the impact on the synthesis of eicosanoids when exposed to low temperatures, it is advisable to study mechanisms for preventing hypothermia independent of cyclooxygenase, particularly the influence on energy metabolism. The aim of the study was to figure out the effect of diclofenac sodium and etoricoxib on the indicators of energy metabolism in the liver of rats after acute general cooling. Experiments were carried out on 28 sexually mature male rats, which were given diclofenac sodium (7 mg/kg), etoricoxib (5 mg/kg), or solvent 30 minutes before cold trauma intragastrically (in the intact control and pathology control groups). Acute hypothermia was caused by exposure of animals for 2 hours at a temperature of -18°C. Rectal temperature was measured before and after acute general cooling. The content of lactate, pyruvate and adenosine triphosphate  in the liver was measured and the lactate/pyruvate ratio was calculated. Diclofenac sodium, unlike etoricoxib, was found to significantly reduce the severity of hypothermia. Both nonsteroidal anti-inflammatory drugs prevent energy metabolism disorders caused by exposure to cold, namely, reducing the concentration of lactic acid and the ratio of lactate/pyruvate, increasing the content of pyruvate and adenosine triphosphate  in the liver of animals. Etoricoxib normalizes the content of energy metabolism intermediates to their levels in intact animals. Diclofenac sodium has a similar effect, the expression of which is inferior to the selective cyclooxygenase-2 inhibitor. Therefore, when administered prophylactically before acute general cooling, diclofenac sodium effectively prevents hypothermia in rats, surpassing etoricoxib. Etoricoxib completely prevents a decrease in the content of pyruvate and adenosine triphosphate, as well as the accumulation of lactic acid in the liver. Diclofenac sodium is inferior to etoricoxib in its effect on energy metabolism, which indicates other mechanisms of frigoprotective action of a non-selective cyclooxygenase inhibitor. The frigoprotective and energotropic properties of nonsteroidal anti-inflammatory drugs dissociate.