Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats
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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.
Keywords:Olanzapine / Chronic social isolation / Liver / Oxidative stress / Inflammation / Histopathology
Source:European Journal of Pharmaceutical Sciences, 2016, 81, 94-102
- Molecular mechanisms of cellular responses on pathological changes in central neuronal system and peripheral organs of mammals (RS-173044)
- Deutsche Forschungsgemeinschaft [SFB636-TP3]