Protective effects of melatonin on long-term administration of fluoxetine in rats

The degree and consequence of tissue injury are highly regarded during long-term exposure to selective antidepressant fluoxetine. Melatonin has been shown to palliate different lesions by scavenging free radicals, but its role in the reduction of the fluoxetine-induced injuries has been little known.

Thirty-six mature male Wistar rats were randomly assigned into control and experimental groups. The experimental rats were included as following; 24 mg/kg/bw fluoxetine for 4 weeks; 1 mg/kg/bw melatonin for 4 weeks; fluoxetine + 1-week melatonin, fluoxetine + 2-week melatonin and fluoxetine + 4-week melatonin. In the current experiment, we investigated weight gain, hematological and biochemical parameters, pathological injuries and oxidative status.

We noted the positive effect of melatonin in weight loss of fluoxetine-treated rats (p < 0.05). The significant reduction of superoxide dismutase, glutathione peroxidase, catalase activities in blood, liver, and kidneys and changes in serum total antioxidant capacity caused by fluoxetine were reversed by melatonin (p < 0.05). Melatonin reduced the increased lipid peroxidation and transaminase activity in rats received fluoxetine (p < 0.05). We also showed the potency of fluoxetine in inducing leukopenia, thrombocytopenia and hypochromic and macrocytic anemia which was blunted by melatonin. Both RBCs and platelets indices were also corrected. Rats received melatonin in combination with fluoxetine showed a reduction in the severity of degeneration and inflammatory changes in different tissues, brain, heart, liver, lungs, testes and kidneys as compared to the fluoxetine group.

Therefore, melatonin fundamentally reversed the side effects of fluoxetine in the rat model which is comparable to human medicine.