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