Invivo antioxidant status: A putative target of antidepressant action

This is an interesting paper from Department of Life Sciences, Aligarh Muslim University. Bilici et al (2001)reported changes Glutathione peroxidase (GSHPx)and Melondialdehyde (p<0.05) in plasma and significant change in (p<0.05)GSH-Px and SOD in erythrocytes-no Melondialdehyde!-of major depression (with or without melancholia) compared to healthy controls. sub chronic reatment of these patients with SSRIs (Sertraline, Fluoxetin, Citalopram and Fluvoxamine) significantly decreased (p<0.01) GSHpx and melondialdehyde in plasma and SOD and Melondialdehyde in erythrocytes. Micheal et al in 2007 reported increased SOD levels in PFC of patient with depressive disorder when compared to controls (vascular problem matched) but the difference was significant in hippocampus.
This paper induces depression in animal models by immobility and measures it by forced swimming and sucrose preference tests both are corrected by antidepressant treatment (Imipramine, Fluoxetine and Venlafexine-most commonly used antidepressant!!)
Their stress model has less SOD, CAT, GST, GR, GSH and incresed MDA and Carbomoyl content compared to controls. Only MDA data is in line with human subjects plama levels so I doubt that this model can indeed give out all features (including molecular) of depression. Neverthless MDA can itself activate PLCA2, oxidize PUFAs and inhibit serotonin receptors. Also SSRI treatment decreased MDA and Carbomoyl levels and restored SOD levels to that comparable to control animals. Which suggests that SSRIs might be fighting oxidative stress and lipid peroxidation might be important feature of such behavioral abnormalities.

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Progress in Neuro-Psychopharmacology and Biological Psychiatry
In Vivo Antioxidant Status: A Putative Target Of Antidepressant Action
In Press, Accepted Manuscript, Available online 30 November 2008
Ayesha Zafir, Anjum Ara, Naheed Banu
Department of Biochemistry, and 2Department of Zoology, Faculty of Life Sciences, A.M.University, Aligarh, U.P., India

Abstract: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, fewanimal studies have investigated the effect of these drugs on endogenous antioxidant status in thebrain. The present study employed a 21-day chronic regimen of random exposure to restraintstress to induce oxidative stress in brain, and behavioural aberrations, in rodents. The forcedswimming (FST) and sucrose preference tests were used to identify depression-like phenotypes,and reversal in these indices indicated the effectiveness of treatment with fluoxetine (FLU; 20mg/kg/day, p.o.; selective serotonin reuptake inhibitor), imipramine (IMI; 10 mg/kg/day, p.o.;
tricyclic antidepressant) and venlafaxine (VEN; 10 mg/kg/day, p.o.; dual serotonin/norepinephrine reuptake inhibitor) following restraint stress. The antioxidant statuswas investigated in the brain of these animals. The results evidenced a significant recovery in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST),glutathione reductase (GR) and glutathione (GSH) levels by antidepressant treatments following a restraint stress-induced decline of these parameters. The severely accumulated lipid peroxidation product malondialdehyde (MDA) and protein carbonyl contents in stressed animals
were significantly normalized by antidepressant treatments. The altered oxidative status is implicated in various aspects of cellular function affecting the brain. Thus, it is possible that augmentation of in vivo antioxidant defenses could serve as a convergence point for multiple classes of antidepressants as an important mechanism underlying the neuroprotective pharmacological effects of these drugs observed clinically in the treatment of various stress disorders. Consequently, pharmacological modulation of stress-induced oxidative damage as a possible stress-management approach should be an important avenue of further research