The anti-inflammatory effects of orexin receptor antagonist on endotoxemia induced sepsis model


Kolgazi Gürcanlı M. , Kılınç E. , Çilingir S.

XXX. National Congress of the Turkish Biochemical Society TBS 2019, Antalya, Türkiye, 26 - 31 Ekim 2019

  • Basıldığı Şehir: Antalya
  • Basıldığı Ülke: Türkiye

Özet

Objectives: Inflammatory diseases, including sepsis, are often accompanied by loss of appetite. As an orexigenic peptite, Orexin increases appetite; however little is known about its role in sepsis related inflammatory conditions. Thus, the aim of the study is to investigate the role of orexin in Escherichia coli lipopolysaccharide (LPS) induced endotoxemia by using its dual receptor antagonist almorexant.

Methods: Sprague Dawley rats (male=female; 250-300g) were used: (1) Control and (2) Endotoxemia (E) groups were treated with saline; (3) E + orexin antagonist group was treated with almorexant (30 mg/kg ip) for 3 days. On the 4th day, saline (control group) or LPS (others) was injected. Six hours after LPS injection, rats were sacrificed; their trunk blood, duodenum, stomach, liver, colon and kidney samples were collected. Tissue samples were analyzed for myeloperoxidase (MPO) activity, malondialdehyde (MDA) and glutathione (GSH) levels and microscopic damage was scored. Cortisol, tumor necrosis factor (TNF)-a, Interleukin (IL)-1b and IL-6 levels were measured in serum samples.

Results: Endotoxemia increased MPO activity, MDA levels in all tissues and caused GSH depletion. MPO activity and MDA levels in all tissues and, cortisol, TNF-a, IL-1b and IL-6 levels in serum were decreased with almorexant injection compared with the endotoxemia group. Microscopic damage scores also reduced. However, almorexant treatment could not prevent GSH depletion induced by endotoxemia.

Conclusion: The results of our research showed that almorexant has anti-inflammatory effects on LPS induced sepsis. Probably, dual orexin receptor antagonist, almorexant showed its anti-inflammatory effects by inhibiting tissue neutrophil infiltration and preventing lipid peroxidation.

Keywords: Orexin, Almorexant, Sepsis, Endotoxemia, inflammation