Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats

• Verfasst von: Todorović, Nevena [VerfasserIn]
• Verfasst von: Gass, Peter [VerfasserIn]
• Titel: Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats
• Verf.angabe: Nevena Todorović, Nada Tomanović, Peter Gass, Dragana Filipović
• Jahr: 2016
• Jahr des Originals: 2015
• Umfang: 9 S.
• Fussnoten: Gesehen am 22.01.2019 ; Available online 19 October 2015
• Titel Quelle: Enthalten in: European journal of pharmaceutical sciences
• Ort Quelle: New York, NY [u.a.] : Elsevier, 1993
• Jahr Quelle: 2016
• Band/Heft Quelle: 81(2016), Seite 94-102
• ISSN Quelle: 1879-0720
• DOI: doi:10.1016/j.ejps.2015.10.010
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Chronic social isolation
• Sach-SW: Histopathology
• Sach-SW: Inflammation
• Sach-SW: Liver
• Sach-SW: Olanzapine
• Sach-SW: Oxidative stress
• K10plus-PPN: 1586487930

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 (7.5mg/kg/day), on rat hepatic glutathione (GSH)-dependent defense and proinflammatory cytokines following 6weeks 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-κB (NF-κB), 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-κB 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-κB 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.