title: Fluoxetine affects antioxidant system and promotes apoptotic signaling in Wistar rat liver.
abstract: Selective serotonin reuptake inhibitors (SSRI) are a treatment of choice for stress related disorders including clinical depression and a range of anxiety-related disorders. In the experimental animals, chronic stress paradigms are considered as a model of depression, and in that context are used for examining the effects of different drug treatments. The present research was designed to investigate the effect of SSRI fluoxetine on antioxidant status and apoptotic signaling in Wistar rat liver, which is a central organ for activation and detoxification of many xenobiotics and reactive oxygen species. We also investigated whether chronic fluoxetine treatment exhibits the same effects in the liver of control animals vs. animals stressed by chronic psychosocial isolation. Our results revealed that fluoxetine downregulated the activity of superoxide dismutases and upregulated the activity of glutathione peroxidase in both rat groups, while elevating glutathione reductase activity and total antioxidant status only in stressed animals. These results suggested that fluoxetine interfered with stress-induced pathways of oxidative defense in the liver. In addition, in both experimental groups, fluoxetine induced several hallmarks of apoptosis in the liver, including a decrease in Bcl-2 expression and increased DNA fragmentation. However, apoptotic alterations were more pronounced in stressed animals, suggesting that stress related oxidative damage could have primed apoptotic effects of fluoxetine.
authors.affiliation: Laboratory of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, P.O. Box-522-MBE090, 11001 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Djordjevic
authors.affiliation: Laboratory of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, P.O. Box-522-MBE090, 11001 Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Djordjevic
authors.affiliation: Laboratory of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, P.O. Box-522-MBE090, 11001 Belgrade, Serbia.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Adzic
authors.affiliation: Department of Biochemistry, Institute for Biological Research Sinisa Stanković, University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Elaković
authors.affiliation: Department of Biochemistry, Institute for Biological Research Sinisa Stanković, University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Matić
authors.affiliation: Laboratory of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, P.O. Box-522-MBE090, 11001 Belgrade, Serbia.
authors.forename: Marija B
authors.initials: MB
authors.lastname: Radojcic
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D005473:Fluoxetine / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005473:Fluoxetine; D019253:Proto-Oncogene Proteins c-bcl-2; D017367:Selective Serotonin Reuptake Inhibitors; D051028:bcl-2-Associated X Protein