Ability of Mexidol to Enhance Antiexudative Effect of Diclofenac Sodium and Etoricoxib in Rats and Mice with Carrageenan-Induced Edema

Nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most widely used drugs in existence. However, they can cause numerous side effects. Therefore, it is crucial to develop approaches to reducing the severity of their side effects. The purpose of this study is to investigate the effect of mexidol on the anti-inflammatory activity of NSAIDs, such as selective cyclooxygenase (COX)-2 inhibitor etoricoxib and nonselective COX inhibitor diclofenac sodium. Effect of a single oral dose of the drugs was evaluated in rats and mice with carrageenan-induced edema by measuring the severity of edema over a period of 4 and 6 h, respectively. Diclofenac sodium at doses of 1 and 10 mg/kg exhibits a dose-dependent antiexudative effect, the effect of etoricoxib at these doses is comparable, and mexidol at a dose of 25 mg/kg does not exhibit an antiexudative effect. In mice, the effect of a combination of diclofenac sodium at a dose of 1 mg/kg and mexidol at a dose of 25 mg/kg is noninferior to diclofenac sodium at a dose of 10 mg/kg and superior to the effect of diclofenac sodium at a dose of 1 mg/kg. In rats, the combination of diclofenac sodium and mexidol significantly reduces the severity of edema at 4 h after its induction compared with diclofenac sodium at a dose of 1 mg/kg only. In mice, a combination of etoricoxib at a dose of 1 mg/kg and mexidol at a dose of 25 mg/kg is more effective than etoricoxib at doses of 1 and 10 mg/kg. In rats, etoricoxib at a dose of 10 mg/kg and the combination of etoricoxib at a dose of 1 mg/kg and mexidol at a dose of 25 mg/kg have a comparable effect. Mexidol at a low dose (25 mg/kg) enhances the antiexudative effect of diclofenac sodium and etoricoxib. Therefore, a decrease in the dose of NSAIDs in combination with mexidol will help to reduce the side effects of these drugs.