In vivo effects of the antidepressant fluoxetine on spleen antioxidant status of C57BL/6 mice were studied using a melanoma experimental model. After a 14-day treatment with fluoxetine (10 mg kg À1 day À1 , i.p.), the endogenous antioxidant non-enzyme (glutathione) and enzyme (superoxide dismutase (SOD) and glutathione peroxidase (GPx)) defense systems in spleen of healthy animals were not changed; the lipid peroxidation (LP) was also unchanged. When B16F10 melanoma cells were introduced in C57BL/6 mice 2 h before fluoxetine treatment, a drug-protective effect against the melanoma-induced oxidative changes (increased LP and decreased total glutathione (GSH)-level, as well as antioxidant enzyme activities) in spleen was observed. Fluoxetine dose-dependently reduced the amounts of free oxygen radicals (hydroxyl and superoxide anion radicals), generated in chemical systems. Taken together, the present results suggest that fluoxetine, acting as antioxidant, prevents from melanoma-induced oxidative changes in mice spleen.

The pathogenesis of many diseases and different pathological conditions, including inflammation, is associated with excess production of reactive oxygen species (ROS). The present study aimed to investigate the effects of the antidepressant desipramine (DES) on carrageenan (CG)-induced inflammation, as well as on the endogenous levels of cell enzyme and non-enzyme antioxidants in rat liver and spleen, 4 and 24 h after CG injection. The intra-plantar CG injection into the right hind paw resulted in a time-dependent increase in the paw volume; the maximum of CG-induced edema peak was in 2-4 h. A single DES dose of 20 mg · kg(-1) , administered 30 min before CG, had no effect on paw edema, whereas the higher drug dose used (50 mg · kg(-1) ) suppressed the edematous response to CG. The latter drug dose protected CG-induced decrease of glutathione (non-enzyme antioxidant) in the liver; it did not affect CG-unchanged activities of superoxide dismutase, glutathione peroxidase (enzyme antioxidants) and glucose-6-phosphate dehydrogenase (enzyme, important for the activity of glutathione-conjugated antioxidant enzymes) in both liver and spleen. The drug showed an efficient antioxidant capacity in ROS-generating chemical systems; it was higher than that of fluoxetine (another type of antidepressant). The present results suggest that the good antioxidant activity of DES might contribute to its beneficial effects in liver injuries.

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