Venlafaxine Modulates Depression-Induced Oxidative Stress in Brain and Medulla of Rat

Abstract

Venlafaxine is an approved antidepressant that is an inhibitor of both serotonin and norepinephrine transporters. Medical treatment with oral venlafaxine can be beneficial to depression due to reducing free radical production in the brain and medulla of depression-induced rats because oxidative stress may a play role in some depression. We investigated the effect of venlafaxine administration and experimental depression on lipid peroxidation and antioxidant levels in cortex brain, medulla and erythrocytes of rats. Thirty male wistar rats were used and were randomly divided into three groups. Venlafaxine (20 mg/kg) was orally supplemented to depression-induced rats constituting the first group for four week. Second group was depression-induced group although third group was used as control. Depressions in the first and second groups were induced on day zero of the study by chronic mild stress. Brain, medulla and erythrocytes samples were taken from all animals on day 28. Depression resulted in significant decrease in the glutathione peroxidase (GSH-Px) activity and vitamin C concentrations of cortex brain, glutathione (GSH) value of medulla although their levels were increased by venlafaxine administration to the animals of depression group. The lipid peroxidation levels in the three tissues and nitric oxide value in cortex brain elevated although their levels were decreased by venlafaxine administration. There were no significant changes in cortex brain vitamin A, erythrocytes vitamin C, GSH-Px and GSH, medulla vitamin A, GSH and GSH-Px values. In conclusion, cortex brain within the three tissues was most affected by oxidative stress although there was the beneficial effect of venlafaxine in the brain of depression-induced rats on investigated antioxidant defenses in the rat model. The treatment of depression by venlafaxine may also play a role in preventing oxidative stress.

Type 1 diabetes mellitus and major depressive disorder: evidence for a biological link

“…Hypercortisolism, which is present in depression (and diabetes), as described below, can also contribute to increased oxidative stress [58,59]. In rodent studies, experimental models of depression (chronic mild stress model) demonstrate that glucocorticoid hypersecretion causes oxidative stress, both by increasing lipid peroxidation in the brain cortex and medulla and by decreasing glutathione levels in the medulla [60]; this finding requires confirmation in humans. Furthermore, antidepressant treatment in humans and animals has been shown to alleviate oxidative stress [54,60].…”

“…In rodent studies, experimental models of depression (chronic mild stress model) demonstrate that glucocorticoid hypersecretion causes oxidative stress, both by increasing lipid peroxidation in the brain cortex and medulla and by decreasing glutathione levels in the medulla [60]; this finding requires confirmation in humans. Furthermore, antidepressant treatment in humans and animals has been shown to alleviate oxidative stress [54,60]. The mechanism by which oxidative stress may cause depression is not known; however, one potential area of investigation is oxidative stress-induced mitochondrial dysfunction, which is characteristic of depression [61] and may induce altered neuronal activity or death [61].…”

Oxidative stress in psychiatric disorders: evidence base and therapeutic implications

“…Data from animal models have demonstrated the depletion of glutathione (Pal and Dandiya, 1994), reduction of GSH-Px and vitamin C, and rise in lipid peroxidation and NO (Eren et al, 2007b) in association with stress-induced behavioural depression.…”

Study of antidepressant effects of grape seed oil in male mice using tail suspension and forced swim tests

“…Induction of depression using chronic stress model significantly reduced activity of glutathione peroxidase in mouse brain cortex. The induction of depression also reduced the levels of glutathione and vitamin C in the cortex and increased lipids peroxidation (Eren et al, 2007).…”

“…Studies have shown that most symptoms of chronic unpredictable stress-induced depression occur due to the impairment of neuroendocrine, anti-oxidant defense, and inflammatory systems (Eren et al, 2007;Mao et al, 200;Marks et al, 2009;You et al, 2011). A study by Schaalan et al (2011), reported neuroendocrine impairment and significant increase in serum adrenocorticotropin and corticosterone levels in mice exposed to chronic unpredictable stress (Schaalan and Nassar, 2011).…”