Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats
Само за регистроване кориснике
2016
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
Olanzapine / Chronic social isolation / Liver / Oxidative stress / Inflammation / HistopathologyИзвор:
European Journal of Pharmaceutical Sciences, 2016, 81, 94-102Издавач:
- Elsevier
Финансирање / пројекти:
- Молекуларни механизми патофизиолошких промена у ћелијама централног нервног система и периферног ткива код сисара (RS-MESTD-Basic Research (BR or ON)-173044)
- Deutsche Forschungsgemeinschaft [SFB636-TP3]
DOI: 10.1016/j.ejps.2015.10.010
ISSN: 0928-0987; 1879-0720
PubMed: 26474692
WoS: 000367787700012
Scopus: 2-s2.0-84944754606
Колекције
Институција/група
VinčaTY - 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 . .