Evidence for protective effect of lipoic acid and desvenlafaxine on oxidative stress in a model depression in mice

Oxidative stress is implicated in the neurobiology of depression. Here we investigated oxidative alterations in brain areas of animals submitted to the model of depression induced by corticosterone (CORT) and the effects of the antioxidant compound alpha-lipoic acid (ALA) alone or associated with the antidepressant desvenlafaxine (DVS) in these alterations. Female mice received vehicle or CORT (20 mg/kg) during 14 days. From the 15th to 21st days different animals received further administrations of: vehicle, DVS (10 or 20 mg/kg), ALA (100 or 200 mg/kg), or the combinations of DVS10 + ALA100, DVS20 + ALA100, DVS10 + ALA200, or DVS20 + ALA200. Twenty-four hours after the last drug administration prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) were dissected for the determination of the activity of superoxide dismutase (SOD), reduced glutathione (GSH) and lipid peroxidation (LP) levels. CORT significantly increased SOD activity in the PFC and HC, decreased GSH levels in the HC and increased LP in all brain areas studied when compared to saline-treated animals. Decrements of SOD activity were observed in all groups and brain areas studied when compared to controls and CORT. The hippocampal decrease in GSH was reversed by ALA100, DVS10 + ALA100, DVS20 + ALA100 and DVS20 + ALA200. The same DVS + ALA combination groups presented increased levels of GSH in the PFC and ST. The greater GSH levels were observed in the PFC, HC and ST of DVS20 + ALA200 mice. LP was reversed in the groups ALA200 (PFC), DVS10 + ALA100, DVS20 + ALA100 (PFC, HC and ST), and DVS20 + ALA200 (PFC, HC). Our findings contribute to the previous preclinical evidences implicating ALA as a promising agent for augmentation therapy in depression.