Oxidative Medicine and Cellular Longevity / 2012 / Article / Tab 3

Review Article

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

Table 3

Animal studies with antidepressant drugs.

Animal modelAntidepressant drugs testedMain findingsReference

Male albino miceAcute treatmentBupropion (10–40 mg/kg), i.p., once, 30 min before brain sample acquisitionModulated the L-arginine-NO-cyclic cGMP signalling pathway in rat brainDhir and Kulkarni, 2007 [13]
Female Swiss miceAcute treatmentEscitalopram (3 mg/kg), p.o., once, 30 min before behavioural testsAntidepressant-like effect was mediated by an inhibition of either the NMDA receptor activation or NO-cGMP synthesisZomkowski et al., 2010 [14]
Male C57Bl/6J miceAcute treatmentImipramine (15 mg/kg), venlafaxine (6 mg/kg), both drugs, i.p., once onlyDecreased brain NO2 + NO3 levels in control miceKrass et al., 2011 [15]
Male Wistar ratsAcute treatmentAmitriptyline (10 mg/kg), i.p., once only, 3 h before analysesDrug did not alter NO2 + NO3 serum levels in control ratsVismari et al., 2012 [16]
Male Wistar ratsAcute and chronic treatmentFluoxetine (20 mg/kg once or 10 mg/kg/day), i.p., once only or once a day for 12 daysShowed stimulation of mitochondrial respiration in state 4 in acute or prolonged treatments, indicating uncoupling of oxidative phosphorylation in rat liver mitochondriaSouza et al., 1994 [7]
Male Wistar ratsAcute and chronic treatmentImipramine (10, 20 and 30 mg/kg), i.p., once only or once a day for 14 daysDecreased MDA and carbonyl content and increased SOD and CAT activity in prefrontal cortex and hippocampusRéus et al., 2010 [17]
Male Wistar ratsAcute and chronic treatmentImipramine (10, 20 and 30 mg/kg), i.p., once only or once a day for 14 daysIncreased brain creatine kinase and mitochondrial respiratory chain activitiesRéus, et al., 2012 [18]
Male Wistar ratsAcute and chronic treatmentImipramine (10, 20 and 30 mg/kg), i.p., once only or once a day for 14 daysAltered respiratory chain complexes and CK activities; these alterations were different with relation to protocols (acute or chronic), complex, dose, and brain areaRéus, et al., 2012 [53]
Female Swiss miceAcute and chronic treatmentFluoxetine (10 mg/kg), p.o., once only or once a day for 28 daysAcute treatment reduced GPx activity in hippocampus; chronic treatment increases GSH in both hippocampus and prefrontal cortexLobato et al., 2010 [19]
Female Wistar ratsChronic treatmentImipramine (10 mg/kg) twice daily, i.p., 1 or 2 weeksPromoted stimulation of the states 3 and 4 respiration rates (1 and 2 week treatments) on rat brain mitochondriaKatyare and Rajan, 1995 [20]
Male Sprague-Dawley ratsChronic treatmentAmitriptyline (5, 10 mg/kg/day), venlafaxine (5, 10 mg/kg/day), both drugs. i.p., for 3 weeksBoth drugs increased SOD immunostaining in the hippocampal neuronsXu et al., 2003 [21]
Male Wistar Han ratsChronic treatmentFluoxetine, 8 and 24 mg/kg/day, p.o., for 4 weeksIncreased levels of carbonyl groups, TBARS, and the uric acid content in the liver, effects more pronounced at high doseInkielewicz-Stêpniak, 2011 [22]
Male Swiss albino miceAcute treatment, with or without previous restraint stress protocolFluoxetine, 5 mg/kg/day, i.p., 30 min before restraint stress protocolPartially reversed the adverse effects of stress (restraint stress significantly increases the generation of ROS in the peripheral defence cells) restoring SOD, CAT, and GSH levelsNovio et al., 2011 [23]
Swiss Albino ratsChronic treatment, with or without previous restraint stress protocolFluoxetine (20 mg/kg/day), imipramine (10 mg/kg/day), venlafaxine (10 mg/kg/day), all drugs, p.o., for 3 weeksAll drugs restored SOD, CAT, GST, and GR activity, increased GSH and decreased MDA and carbonyl in brain samples of stressed animalsZafir et al., 2009 [24]
Male Wistar ratsChronic treatment, with or without previous chronic social isolation stressFluoxetine, 5 mg/kg/day, i.p., for 3 weeksDecreased SOD and increased GPx activity in both groups, increased TAC in stressed animals, also induced several hallmarks of apoptosis in the liver of stressed animalsDjordjevic et al., 2011 [25]
Male Swiss-Webster miceChronic treatment, stress induced by FST and TSTVenlafaxine (5, 10, and 20 mg/kg/day), i.p. for 3 weeksDecreased MDA and NO and increased hippocampal GSH and TAC levels and GST activity in the stressed animals, also, reduced both serum and hippocampal 8-OHdG levelsAbdel-Wahab and Salama, 2011 [26]

8-OHdG: 8-hydroxydeguanosine; CAT: catalase; cGMP: cyclic guanosine monophosphate; CK: creatine kinase; FST: forced swimming test; GPx: glutathione peroxidase; GR: glutathione reductase; GSH: glutathione; GST: glutathione S-transferase; MDA: malondialdehyde; NO: nitric oxide; NO2 + NO3, total nitrite + nitrate; ROS: reactive oxygen species; SOD: superoxide dismutase; TAC: total antioxidant capacity; TBARS: thiobarbituric acid reactive species; TST: tail suspension test.

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