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

• Published in: European journal of pharmaceutical sciences Vol. 81; pp. 94 - 102
• Main Authors: Todorović, Nevena, Tomanović, Nada, Gass, Peter, Filipović, Dragana
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-01-2016
• Subjects: Animals; Antipsychotic Agents - pharmacology; Benzodiazepines - pharmacology; Catalase - metabolism; Chronic social isolation; Cytokines - metabolism; Glutathione - metabolism; Glutathione Peroxidase - metabolism; Glutathione Reductase - metabolism; Glutathione Transferase - metabolism; Histopathology; Inflammation; Inflammation - metabolism; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; NF-kappa B - metabolism; Nitric Oxide Synthase Type II - metabolism; Olanzapine; Oxidative stress; Oxidative Stress - drug effects; Rats, Wistar; Social Isolation; Oxidative stress; Olanzapine; Histopathology; Olanzapine (PubChem CID: 11163889); Liver; Inflammation; Chronic social isolation
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2015.10.010

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.
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