Effect of Cyclooxygenase Inhibitors Etoricoxib and Diclofenac Sodium and Their Combinations with Mexidol on Blood Pressure and Hematological Indices in Rats

The effect on blood pressure (BP), hematological indices, and body weight of rats was evaluated for nonselective cyclooxygenase (COX) inhibitor diclofenac sodium (1 and 5 mg/kg) and selective COX-2 inhibitor etoricoxib (1 and 10 mg/kg), 2-ethyl-6-methyl-3-hydroxypyridine succinate (mexidol, 25 mg/kg) and combinations of these nonsteroidal anti-inflammatory drugs (NSAIDs, 1 mg/kg) with mexidol administered per os as a 2- and 3-week daily course. BP increase was observed in rats after 3 weeks of NSAID administration. Specifically, etoricoxib at both doses increased the systolic and diastolic pressures, while diclofenac sodium at a dose of 5 mg/kg only affected the diastolic pressure. Mexidol prevented the BP increase when taken together with etoricoxib. The administration of NSAIDs at maximum doses for 2 weeks was associated with an increase in certain leukocyte type counts. Furthermore, diclofenac sodium increased the number of platelets and induced iron-deficiency anemia, indicating the NSAID-induced enteropathy. Both NSAIDs were shown to negatively affect the dynamics of weight gain in rats, with diclofenac sodium having a more pronounced effect. The combination of diclofenac sodium and etoricoxib with mexidol did not enhance the negative effects of NSAIDs on hematological parameters and weight gain in rats.