title: Nesfatin-1 alleviates gastric damage via direct antioxidant mechanisms.
abstract: BACKGROUND
  Indomethacin is a nonsteroidal anti-inflammatory drug, which is known to produce serious side effects, causing ulcerative lesions. Nesfatin-1, a newly identified anorexigenic peptide, was recently shown to have neuroprotective effects. The aim of the study was to investigate the anti-inflammatory effects of nesfatin-1 on indomethacin-induced gastric ulcer.
  
  
  METHODS
  After a 24-h starvation period, ulcer was induced in Sprague-Dawley rats by subcutaneous administration of indomethacin (25 mg/kg), whereas control group received vehicle. Fifteen minutes after ulcer induction, rats were treated with either saline or nesfatin-1 (0.1, 0.3, or 1 μg/kg, intraperitoneally). At the fourth hour, all rats were decapitated and their trunk blood was collected for tumor necrosis factor (TNF)-α and interleukin (IL)-6 measurements. Stomach samples were examined microscopically and analyzed for myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), luminol-, and lucigenin-enhanced chemiluminescence (CL) levels.
  
  
  RESULTS
  Ulcer induction increased serum TNF-α; and IL-6 levels, gastric CL and MDA levels and MPO activity but decreased gastric GSH content (P < 0.05-0.001). On the other hand, 0.1 μg/kg dose of nesfatin-1 reduced microscopic and macroscopic damage scores, decreased MPO activity and MDA levels, CL and IL-6 levels, whereas gastric GSH was replenished (P < 0.01). However, indomethacin-induced increase in TNF-α level was abolished at only 1 μg/kg dose of nesfatin-1 (P < 0.01).
  
  
  CONCLUSIONS
  Nesfatin-1 alleviated indomethacin-induced gastric injury, suggesting that the anti-inflammatory and gastroprotective effects of nesfatin-1 on oxidative gastric damage could be implemented by supporting the balance in oxidant and antioxidant systems while inhibiting the generation of pro-inflammatory mediators.
authors.affiliation: Department of Physiology, Acibadem University School of Medicine, Istanbul, Turkey.
authors.forename: Meltem
authors.initials: M
authors.lastname: Kolgazi
authors.affiliation: Department of Physiology, Marmara University School of Medicine, Istanbul, Turkey.
authors.forename: Cigdem
authors.initials: C
authors.lastname: Cantali-Ozturk
authors.affiliation: Department of Physiology, Marmara University School of Medicine, Istanbul, Turkey.
authors.forename: Rabia
authors.initials: R
authors.lastname: Deniz
authors.affiliation: Department of Physiology, Marmara University School of Medicine, Istanbul, Turkey.
authors.forename: Zarife Nigar
authors.initials: ZN
authors.lastname: Ozdemir-Kumral
authors.affiliation: Department of Medical Laboratory, Marmara University Vocational School of Health-Related Professions, Istanbul, Turkey.
authors.forename: Meral
authors.initials: M
authors.lastname: Yuksel
authors.affiliation: Department of Histology and Embryology, Marmara University School of Medicine, Istanbul, Turkey.
authors.forename: Serap
authors.initials: S
authors.lastname: Sirvanci
authors.affiliation: Department of Physiology, Marmara University School of Medicine, Istanbul, Turkey. Electronic address: byegen@marmara.edu.tr.
authors.forename: Berrak C
authors.initials: BC
authors.lastname: Yeğen
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology*; D001067:Appetite Depressants / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007213:Indomethacin / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D000080866:Nucleobindins; D009195:Peroxidase / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001067:Appetite Depressants; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D009195:Peroxidase; D005978:Glutathione; D007213:Indomethacin
keywords: Antioxidant; Gastric damage; Indomethacin; Nesfatin-1; Ulcer