Effects of Fluoxetine on the Oxidative Status of Peripheral Blood Leucocytes of Restraint-Stressed Mice

Abstract

Emotional stress can be viewed as a cause of adverse circumstances that induces a wide range of biochemical and behavioural changes. Oxidative stress is a critical route of damage in various psychological stress-induced disorders such as depression. Antidepressants are widely prescribed to treat these conditions; however, no animal study has investigated the effect of selective serotonin reuptake inhibitors (SSRIs) on the levels of intracellular reactive oxygen species in peripheral blood leucocytes of stressed mice. In this study, mice were immobilized for a period of 6 hr. Fluoxetine (5 mg ⁄ kg of bodyweight) was administered 30 min. before subjecting the animals to acute stress. The level of intracellular reactive oxygen species in leucocytes of the peripheral blood of stressed mice was investigated using a 2¢,7¢-dichlorofluorescein diacetate probe, and the antioxidant response of fluoxetine was evaluated by superoxide dismutase, diaphorase, catalase and reduced glutathione. Our results show that restraint stress significantly increases the generation of reactive oxygen species in the peripheral defence cells. Treatment with fluoxetine partially reverses the adverse effects of stress. The improvement in cellular oxidative status may be an important mechanism underlying the protective pharmacological effects of fluoxetine, which are clinically observed in the treatment of depressive disorders.

Antidepressant fluoxetine and its potential against colon tumors

“…Treatment with FLX was found to reduce malondialdehyde (MDA) and carbonyl levels in stressed rats, whilst it enhanced superoxide dismutase (SOD), catalase, glutathione S-transferase, glutathione reductase and glutathione contents [45,46] . Similar findings were reported by another research group [48] . Then, this compound showed neuroprotective effects, decreasing the translocation of p67 protein and ROS generation (by suppressing the activation of nicotinamide adenine dinucleotide phosphate-oxidase oxidase and inducible nitric oxide synthase) in rats exposed to lipopolysaccharide [47] .…”

“…In these epithelial cells, it induces an increase in serotonin (5-HT) levels by blocking L-monoamine oxidase and serotonin reuptake transporters [41][42][43] . On the other hand, FLX has been shown to interfere with the OS machinery in experimental models and humans [44][45][46][47][48][49][50][51][52][53][54][55] . Treatment with FLX was found to reduce malondialdehyde (MDA) and carbonyl levels in stressed rats, whilst it enhanced superoxide dismutase (SOD), catalase, glutathione S-transferase, glutathione reductase and glutathione contents [45,46] .…”

Effect of Anti-stress Activity of Fluoxetine on Restrained Stress Induced Male Albino Rats in Hematological Parameters and Whole Brain Histopathology

“…Considering the ROS-scavenging potential of monoamines, this effect of Fluoxetine imposes a limitation on free radical reactions and concentration of their products. 24 Increased glutaminergic transmission is characteristic of depression. 25 High levels of glutamate, in terms of pathological, can cause excitotoxicity by allowing high levels of calcium ions to enter the cell, which, if present in excess, stimulate the production of ROS.…”

Study of the effect of antidepressant drugs and donepezil on aluminum-induced memory impairment and biochemical alterations in rats

“…The level of GSH in the brain was also increased by the SSRIs in these studies. Other researchers have also reported the ability of different antidepressant drugs to modulate nitric oxide production (Horikawa et al 2010;Krass et al 2011;Liu et al 2011;Michalakeas et al 2011) and brain glutathione (Lobato et al 2010;Novío et al 2011). In depressed patients with chronic heart failure, sertraline treatment decreased the elevated plasma levels of the oxidative stress marker MDA (Michalakeas et al 2011).…”