NSAIDs are promising agents for preventing cold injury (frigoprotectors). The influence of prophylactic administration of the non-selective COX inhibitor diclofenac sodium (7 mg/kg) and the highly selective COX-2 inhibitor etoricoxib (5 mg/kg) on cyclooxygenase pathway biomarkers was studied on the model of acute general cooling (air hypothermia at -18 °С for 2 hours). Diclofenac completely prevented a decrease in body temperature, surpassing etoricoxib. In the liver of the rats immediately after cold exposure, the content of COX-1 was increased moderately and the content of COX-2 highly significantly. Very significantly, the level of PGE2 decreased, and the levels of PGF2α, especially PGI2 and TXB2, were elevated. In the blood serum, the level of COX-1 was decreased, and the changes in COX-2 and prostaglandins levels were similar to those in the liver. Diclofenac exerted a moderate effect towards the normalization of both COX isoforms in the liver, moderately increased the content of PGE2, and decreased - PGF2α and TXB2 without changing the level of PGI2. In serum, diclofenac reduced COX-1 level to subnormal values, and its effect on other biomarkers was similar to that in the liver, except for a moderate decrease in PGI2. Thus, diclofenac was inferior to etoricoxib, which normalized COX-1, COX-2, PGE2, and PGI2 in the liver and reduced the content of PGF2α and TXB2 in the liver to subnormal values. At the same time, in the blood serum, it decreased COX-1, COX-2, and PGE2 to subnormal values, normalized PGF2α, and PGI2, and significantly reduced TXB2. The opposite degree of intensity of the influence of diclofenac and etoricoxib on the cyclooxygenase pathway and body temperature indicates a dissociation of anti-inflammatory and frigoprotective activity. Inhibition of oxidative stress is not determinative for the frigoprotective activity of NSAIDs since diclofenac, despite the weaker influence on the content of 8-isoprostane in the liver, still exerts the maximum frigoprotective activity.
Keywords: Body temperature; body temperature; cold injury prevention; cyclooxygenase; diclofenac sodium; etoricoxib; frigoprotective activity; prostaglandins.