Gastroprotective effect of orexin-A and heme oxygenase system

• Published in: The Journal of surgical research 2015-02, Vol.193 (2), p.626-633
• Main Authors: Gemici, Burcu, PhD, Tan, Ruken, PhD, Birsen, İlknur, MSc, İzgüt Uysal, V. Nimet, PhD
• Format: Article
• Language: English
• Subjects: Animals; Drug Evaluation, Preclinical; Gastric; Heme Oxygenase (Decyclizing) - metabolism; Heme oxygenase-1; Heme Oxygenase-1 - metabolism; Heme oxygenase-2; Intracellular Signaling Peptides and Proteins - pharmacology; Intracellular Signaling Peptides and Proteins - therapeutic use; Ischemia–reperfusion; Lesion; Male; Malondialdehyde - analogs & derivatives; Malondialdehyde - metabolism; Neuropeptides - pharmacology; Neuropeptides - therapeutic use; Neurotransmitter Agents - pharmacology; Neurotransmitter Agents - therapeutic use; Orexin-A; Orexins; Peroxidase - metabolism; Random Allocation; Rats, Wistar; Reperfusion Injury - prevention & control; Stomach - drug effects; Stomach - enzymology; Surgery; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2014.08.048

Abstract Background Orexin-A, besides playing an important role in the mechanism of food intake, exhibits a potent gastroprotective action against the formation of acute gastric mucosal injury. The aim of the present study was to determine the effect of administered orexin-A against ischemia–reperfusion (I/R)-induced gastric injury on the expression of heme oxygenase (HO)-1 and HO-2 in gastric tissue. Materials and methods Wistar rats were subjected to 30 min of ischemia followed by 3 h reperfusion. Orexin-A was infused at a dose of 500 pmol/kg/min during the I/R period. The lesion area was measured by stereomicroscope. The myeloperoxidase activity and 4-hydroxinonenol-malondialdehyde content of gastric mucosa were evaluated spectrophotometrically, and the gastric tumor necrosis factor-α was measured by enzyme linked immune sorbent assay. The expression of HO-1 and HO-2 was determined by Western blotting analysis. Results Orexin-A significantly decreased the I/R-induced gastric lesions, myeloperoxidase activity, and 4-hydroxinonenol-malondialdehyde concentration in gastric tissue exposed to I/R. The gastroprotective effect of orexin-A in gastric I/R model was accompanied by the increase in HO-2 expression and the decrease in HO-1 expression. Conclusions Orexin-A exerts a protective action on gastric mucosa subjected to I/R, and this effect is associated with the reduction of neutrophil infiltration and lipid peroxidation in gastric tissue in addition to the increase in HO-2 expression due to the administration of orexin-A.