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.
Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
Márcia Calheiros Chaves
MC
Silva
Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
Caren Nádia Soares
CN
de Sousa
Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
Patrícia Xavier Lima
PX
Gomes
Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
Gersilene Valente
GV
de Oliveira
Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
Fernanda Yvelize Ramos
FY
Araújo
Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
Naiara Coelho
NC
Ximenes
Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
Jéssica Calheiros
JC
da Silva
Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
Germana Silva
GS
Vasconcelos
Department of Pharmacy, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Luzia Kalyne Almeida Moreira
LK
Leal
Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
Danielle
D
Macêdo
Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil. Electronic address: silvania_vasconcelos@yahoo.com.br.
Silvânia Maria Mendes
SM
Vasconcelos
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D000069468:Desvenlafaxine Succinate / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D013482:Superoxide Dismutase / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*
D000928:Antidepressive Agents; D000975:Antioxidants; D008063:Thioctic Acid; D013482:Superoxide Dismutase; D005978:Glutathione; D003345:Corticosterone; D000069468:Desvenlafaxine Succinate
Augmentation therapy in depression; Depression; Desvenlafaxine; Lipoic acid; Oxidative stress