title: Fluoxetine and the mitochondria: A review of the toxicological aspects.
abstract: Fluoxetine (a selective serotonin reuptake inhibitor (SSRI)) is used as an antidepressant by modulating the levels of serotonin in the synaptic cleft. Nevertheless, fluoxetine also induces undesirable effects, such as anxiety, sexual dysfunction, sleep disturbances, and gastrointestinal impairments. Fluoxetine has been viewed as an agent that may interfere with cell fate by triggering apoptosis. On the other hand, fluoxetine intake has been associated with increased cancer risk. Nonetheless, data remain contradictory and no conclusions were taken. Several studies demonstrated that fluoxetine interacts with mitochondria triggering apoptosis and/or altering mitochondrial function by modulating the activity of respiratory chain components and enzymes of the Krebs cycle. Furthermore, fluoxetine affects mitochondria-related redox parameters in different experimental models. In this review, data demonstrating the effects of fluoxetine upon mammalian mitochondria are described and discussed, as well as several unsolved questions in this field of research are addressed. A separate section deals with future needs regarding the research involving the impact of fluoxetine treatment upon mitochondria and mitochondria-related signaling.
authors.affiliation: Department of Chemistry/ICET, Federal University of Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, CEP 78060-900 Cuiaba, MT, Brazil. Electronic address: mrobioq@gmail.com.
authors.forename: Marcos Roberto
authors.initials: MR
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D004347:Drug Interactions; D004579:Electron Transport / Q000187:drug effects; D005473:Fluoxetine / Q000009:adverse effects*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic
chemical_list: D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Apoptosis; Fluoxetine; Mitochondria; Reactive oxygen species; Respiratory chain