Antioxidant potential of fluoxetine in comparison to Curcuma longa in restraint-stressed rats

Stress plays a potential role in the onset and exacerbation of depression. Chronic restraint stress in rats, and psychosocial stress in humans, is implicated in the pathophysiology of mood and anxiety disorders. Oxidative damage is an established outcome of restraint stress, which has been suggested to induce many damaging processes contributing to the pathology of stress-induced depression. However, the modulatory role of clinically effective antidepressants, such as fluoxetine, in attenuating oxidative stress has not been well characterized. Therefore, the current study was designed to investigate the antioxidant effects of chronic treatment with fluoxetine in animals submitted to restraint stress. The antioxidant potential of the antidepressant fluoxetine was compared with that of turmeric, used as a standard since it integrates both antioxidant and antidepressant properties. Chronic fluoxetine administration to stressed animals for 21 days prevented restraint stress-induced oxidative damage with an efficacy similar to that of turmeric, as evidenced by significant enhancement of key endogenous antioxidant defense components, comprising the free-radical scavenging enzymes, superoxide:superoxide oxidoreductase (EC 1.15.1.1), hydrogen-peroxide:hydrogen-peroxide oxidoreductase (EC 1.11.1.6), glutathione S-transferase (EC 2.5.1.18) and glutathione:NADP+oxidoreductase (EC 1.8.1.7), as well as non-enzymatic antioxidants, GSH, glucose and uric acid, which were severely depleted by restraint stress in animals receiving no treatment. Oxidative stress markers, (S)-lactate:NAD+ oxidoreductase activity (EC 1.1.1.27), malondialdehyde levels (lipid peroxidation product) and protein carbonyl content were also significantly decreased following fluoxetine treatment. Both these drugs when given alone to non-stressed animals did not alter basal levels of antioxidant defense components and oxidative stress markers significantly. Our findings suggest that the therapeutic efficacy of fluoxetine may be mediated, at least partially, via reversal of oxidative damage as demonstrated by protective enhancement of antioxidant status following a stress-induced decline. In addition, this study demonstrates important implications for pharmacological interventions targeting cellular antioxidants as a promising strategy for protecting against oxidative insults in stress-induced depression.