TY  - JOUR
AU  - Perić, Ivana
AU  - Stanisavljević, Andrijana
AU  - Gass, Peter
AU  - Filipović, Dragana
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1806
AB  - Exposure of an organism to chronic social isolation (CSIS) has been shown to have an important role in depression. Fluoxetine (Flx) is a first-line treatment for depression; however, its downstream mechanisms of action beyond serotonergic signaling remain ill-defined. We investigated the effect of 3 weeks of Flx (15 mg/kg/day) treatment on behavioral changes and protein expression/activity of the GSH-dependent defense system, including reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GLR), and glutathione S-transferase (GST), as well as catalase (CAT), in the hippocampus of rats exposed to 6 weeks of CSIS. The subcellular distributions of nuclear factor-kappa B (NF-kappa B), as well as, cytosolic IL-1 beta and IL-6 protein expression, were also determined. CSIS induced depressive- and anxiety-like behaviors, evidenced by a decrease in sucrose preference and an increase in the number of buried marbles. Moreover, CSIS compromised redox homeostasis, targeting enzymes such as GPx, CAT, GST, and caused NF-kappa B nuclear translocation with a concomitant increase in IL-6 protein expression, without an effect on IL-1 beta. Flx treatment reversed CSIS-induced depressive- and anxiety-like behaviors, modulated GSH-dependent defense by increasing GLR and GST activity, and suppressed NF-kappa B activation and cytosolic IL-6 protein expression in socially isolated rats. The present study suggests that changes in the GSH-dependent defense system, NF-kappa B activation and increased IL-6 protein expression may have a role in social isolation-induced changes in a rat model of depression and anxiety, and contributes to our understanding of the mechanisms that underlie the antidepressant and anti-inflammatory activity of Flx in socially isolated rats.
T2  - European Archives of Psychiatry and Clinical Neuroscience
T1  - Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines
VL  - 267
IS  - 8
SP  - 737
EP  - 749
DO  - 10.1007/s00406-017-0807-9
ER  - 

@article{
author = "Perić, Ivana and Stanisavljević, Andrijana and Gass, Peter and Filipović, Dragana",
year = "2017",
abstract = "Exposure of an organism to chronic social isolation (CSIS) has been shown to have an important role in depression. Fluoxetine (Flx) is a first-line treatment for depression; however, its downstream mechanisms of action beyond serotonergic signaling remain ill-defined. We investigated the effect of 3 weeks of Flx (15 mg/kg/day) treatment on behavioral changes and protein expression/activity of the GSH-dependent defense system, including reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GLR), and glutathione S-transferase (GST), as well as catalase (CAT), in the hippocampus of rats exposed to 6 weeks of CSIS. The subcellular distributions of nuclear factor-kappa B (NF-kappa B), as well as, cytosolic IL-1 beta and IL-6 protein expression, were also determined. CSIS induced depressive- and anxiety-like behaviors, evidenced by a decrease in sucrose preference and an increase in the number of buried marbles. Moreover, CSIS compromised redox homeostasis, targeting enzymes such as GPx, CAT, GST, and caused NF-kappa B nuclear translocation with a concomitant increase in IL-6 protein expression, without an effect on IL-1 beta. Flx treatment reversed CSIS-induced depressive- and anxiety-like behaviors, modulated GSH-dependent defense by increasing GLR and GST activity, and suppressed NF-kappa B activation and cytosolic IL-6 protein expression in socially isolated rats. The present study suggests that changes in the GSH-dependent defense system, NF-kappa B activation and increased IL-6 protein expression may have a role in social isolation-induced changes in a rat model of depression and anxiety, and contributes to our understanding of the mechanisms that underlie the antidepressant and anti-inflammatory activity of Flx in socially isolated rats.",
journal = "European Archives of Psychiatry and Clinical Neuroscience",
title = "Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines",
volume = "267",
number = "8",
pages = "737-749",
doi = "10.1007/s00406-017-0807-9"
}

Perić, I., Stanisavljević, A., Gass, P.,& Filipović, D.. (2017). Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines. in European Archives of Psychiatry and Clinical Neuroscience, 267(8), 737-749.
https://doi.org/10.1007/s00406-017-0807-9

Perić I, Stanisavljević A, Gass P, Filipović D. Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines. in European Archives of Psychiatry and Clinical Neuroscience. 2017;267(8):737-749.
doi:10.1007/s00406-017-0807-9 .

Perić, Ivana, Stanisavljević, Andrijana, Gass, Peter, Filipović, Dragana, "Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines" in European Archives of Psychiatry and Clinical Neuroscience, 267, no. 8 (2017):737-749,
https://doi.org/10.1007/s00406-017-0807-9 . .

TY  - JOUR
AU  - Todorović, Nevena
AU  - Tomanović, Nada
AU  - Gass, Peter
AU  - Filipović, Dragana
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/883
AB  - Olanzapine, an atypical antipsychotic, is efficient in stress associated psychiatric diseases, but its effect on the liver, a primary organ for drug activation and detoxification, still remains unclear. The effect of olanzapine administration (7.5 mg/kg/day), on rat hepatic glutathione (GSH)-dependent defense and proinflammatory cytokines following 6 weeks of chronic social isolation (CSIS), which causes depressive-and anxiety-like behavior in adult male Wistar rats, was investigated. The subcellular distribution of nuclear factor-kappa B (NF-kappa B), cytosolic inducible nitric oxide synthase (iNOS) protein levels and hepatic histological alterations were also determined. Decreased GSH content and glutathione reductase activity associated with increased catalase and glutathione S-transferase activity following CSIS indicated hepatic oxidative stress. Moreover, CSIS caused NF-kappa B nuclear translocation and the concomitant increase in iNOS together with increase in interleukin-1beta and tumor necrosis factor alpha protein levels, but no effect on interleukin-6. Olanzapine treatment suppressed NF-kappa B activation and iNOS expression and caused modulation of GSH-dependent defense systems but failed to reverse CSIS-induced increase in hepatic proinflammatory cytokines. Portal inflammation, focal hepatocyte necrosis and an increased number of Kupffer cells in CSIS rats (vehicle-or olanzapine-treated) were found. Olanzapine-treated socially reared rats showed portal inflammation and focal hepatocyte necrosis. Data suggest that CSIS compromised GSH-dependent defense, triggered a proinflammatory response and histological alterations in rat liver. Olanzapine treatment partially reversed the alterations in hepatic GSH-dependent defense, but showed no anti-inflammatory effect suggesting that it may provide protective effect against hepatic CSIS-induced oxidative stress, but not against inflammation. (C) 2015 Elsevier B.V. All rights reserved.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats
VL  - 81
SP  - 94
EP  - 102
DO  - 10.1016/j.ejps.2015.10.010
ER  - 

@article{
author = "Todorović, Nevena and Tomanović, Nada and Gass, Peter and Filipović, Dragana",
year = "2016",
abstract = "Olanzapine, an atypical antipsychotic, is efficient in stress associated psychiatric diseases, but its effect on the liver, a primary organ for drug activation and detoxification, still remains unclear. The effect of olanzapine administration (7.5 mg/kg/day), on rat hepatic glutathione (GSH)-dependent defense and proinflammatory cytokines following 6 weeks of chronic social isolation (CSIS), which causes depressive-and anxiety-like behavior in adult male Wistar rats, was investigated. The subcellular distribution of nuclear factor-kappa B (NF-kappa B), cytosolic inducible nitric oxide synthase (iNOS) protein levels and hepatic histological alterations were also determined. Decreased GSH content and glutathione reductase activity associated with increased catalase and glutathione S-transferase activity following CSIS indicated hepatic oxidative stress. Moreover, CSIS caused NF-kappa B nuclear translocation and the concomitant increase in iNOS together with increase in interleukin-1beta and tumor necrosis factor alpha protein levels, but no effect on interleukin-6. Olanzapine treatment suppressed NF-kappa B activation and iNOS expression and caused modulation of GSH-dependent defense systems but failed to reverse CSIS-induced increase in hepatic proinflammatory cytokines. Portal inflammation, focal hepatocyte necrosis and an increased number of Kupffer cells in CSIS rats (vehicle-or olanzapine-treated) were found. Olanzapine-treated socially reared rats showed portal inflammation and focal hepatocyte necrosis. Data suggest that CSIS compromised GSH-dependent defense, triggered a proinflammatory response and histological alterations in rat liver. Olanzapine treatment partially reversed the alterations in hepatic GSH-dependent defense, but showed no anti-inflammatory effect suggesting that it may provide protective effect against hepatic CSIS-induced oxidative stress, but not against inflammation. (C) 2015 Elsevier B.V. All rights reserved.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats",
volume = "81",
pages = "94-102",
doi = "10.1016/j.ejps.2015.10.010"
}

Todorović, N., Tomanović, N., Gass, P.,& Filipović, D.. (2016). Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats. in European Journal of Pharmaceutical Sciences
Elsevier., 81, 94-102.
https://doi.org/10.1016/j.ejps.2015.10.010

Todorović N, Tomanović N, Gass P, Filipović D. Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats. in European Journal of Pharmaceutical Sciences. 2016;81:94-102.
doi:10.1016/j.ejps.2015.10.010 .

Todorović, Nevena, Tomanović, Nada, Gass, Peter, Filipović, Dragana, "Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats" in European Journal of Pharmaceutical Sciences, 81 (2016):94-102,
https://doi.org/10.1016/j.ejps.2015.10.010 . .