Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder

Table 2

In vitro studies with antidepressants.

Method		Antidepressant drugs tested	Main findings	Reference
In vitro	Rat brain mitochondria	Fluoxetine	Indirectly and nonspecifically affects electron transport and F1F0-ATPase activity inhibiting oxidative phosphorylation	Curti et al., 1999 [6]
In vitro	Rat liver mitochondria	Fluoxetine	Multiple effects on the energy metabolism of rat liver mitochondria; potentially toxic in high doses	Souza et al., 1994 [7]
In vitro	Rat liver mitochondria	Fluoxetine	Inhibits the opening of the MPT pore, the release of cytC, and protected against staurosporine-induced apoptotic cell death	Nahon et al., 2005 [8]
In vitro	Rat liver mitochondria	Nortriptyline	Inhibits loss of mitochondrial membrane potential and the activation of caspase 3	Zhang et al., 2008 [9]
Cell culture	PCN cells oxygen/glucose deprived	Nortriptyline	Decrease cell death	Zhang et al., 2008 [9]
Cell culture	PC12 cells exposed to H2O2	Amitriptyline, fluoxetine	Both agents attenuated cell death induced by H2O2, fluoxetine pretreatment increased SOD activity	Kolla et al., 2005 [10]
Cell culture	IFN-γ-activated microglia	Fluvoxamine, imipramine, reboxetine	All drugs inhibited IL-6 and NO production in a dose-dependent manner	Hashioka et al., 2007 [11]
Cell culture	Human monocytic U-937 cells	Desipramine, imipramine, maprotiline, and mirtazapine	Short-term treatment decreased mRNA levels of SOD and CAT after treatment with these drugs; long-term treatment increased mRNA levels of SOD, GST, and GR	Schmidt et al., 2008 [12]

CAT: catalase; cytC: cytochrome C; GR: glutathione reductase; GST: glutathione S-transferase; H₂O₂: hydrogen peroxide; IFN-γ: interferon-gamma; IL-6: interleukin 6; MPT: mitochondrial permeability transition; NO: nitric oxide; SOD: superoxide dismutase.