title: Inhibiting renin angiotensin system in rate limiting step by aliskiren as a new approach for preventing indomethacin induced gastric ulcers.
abstract: OBJECTIVE
  Previously blocking the renin angiotensin system (RAAS) has been effective in the prevention of gastric damage. Therefore, the aim of this study was to investigate the effects of aliskiren, and thus, direct renin blockage, in indomethacin-induced gastric damage model.
  
  
  METHODS
  Effects of aliskiren were evaluated in indomethacin-induced gastric damage model on Albino Wistar rats. Effects of famotidine has been investigated as standard antiulcer agent. Stereological analyses for ulcer area determination, biochemical analyses for oxidative status determination and molecular analyses for tissue cytokine and cyclooxygenase determination were performed on stomach tissues. In addition, to clarify antiulcer effect mechanism of aliskiren pylorus ligation-induced gastric acid secretion model was applied on rats.
  
  
  RESULTS
  Aliskiren was able to inhibit indomethacin-induced ulcer formation. It also inhibited renin, and thus, decreased over-produced Angiotensin-II during ulcer formation. Aliskiren improved the oxidative status and cytokine profile of the stomach, which was most probably impaired by increased Angiotensin II concentration. Aliskiren also increased gastroprotective prostaglandin E2 concentration. Finally, aliskiren did not change the gastric acidity in pylorus ligation model.
  
  
  CONCLUSIONS
  Aliskiren exerted its protective effects on stomach tissue by decreasing inflammatory cytokines and oxidative stress as a result of inhibiting the RAAS, at a rate-limiting step, as well as its end product, angiotensin II. Aliskiren also significantly increased protective factors such as PGE2, but not affect aggressive factors such as gastric acidity.
authors.affiliation: Department of Pharmacology, Ataturk University, Faculty of Medicine, Erzurum, Turkey.
authors.forename: Zekai
authors.initials: Z
authors.lastname: Halici
authors.affiliation: Department of Pharmacology, Ataturk University, Faculty of Pharmacy, Erzurum, Turkey.
authors.forename: Beyzagul
authors.initials: B
authors.lastname: Polat
authors.affiliation: Department of Pharmacology, Ataturk University, Faculty of Medicine, Erzurum, Turkey. Electronic address: ecadirci@atauni.edu.tr.
authors.forename: Elif
authors.initials: E
authors.lastname: Cadirci
authors.affiliation: Department of Pharmacology, Recep Tayyip Erdoğan University, Faculty of Medicine, Rize, Turkey.
authors.forename: Atilla
authors.initials: A
authors.lastname: Topcu
authors.affiliation: Department of Pharmacology and Toxicology, Ataturk University, Faculty of Veterinary Medicine, Erzurum, Turkey.
authors.forename: Emre
authors.initials: E
authors.lastname: Karakus
authors.affiliation: Department of Pharmacology, Ataturk University, Faculty of Medicine, Erzurum, Turkey.
authors.forename: Duygu
authors.initials: D
authors.lastname: Kose
authors.affiliation: Department of Pharmacology, Ataturk University, Faculty of Medicine, Erzurum, Turkey.
authors.forename: Abdulmecit
authors.initials: A
authors.lastname: Albayrak
authors.affiliation: Department of Biochemistry, Ataturk University, Faculty of Pharmacy, Erzurum, Turkey.
authors.forename: Yasin
authors.initials: Y
authors.lastname: Bayir
mesh_terms: D000577:Amides / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005650:Fumarates / Q000494:pharmacology* / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin; D007700:Kinetics; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013270:Stomach / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000188:drug therapy* / Q000235:genetics / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000577:Amides; D016207:Cytokines; D005650:Fumarates; D012333:RNA, Messenger; D008315:Malondialdehyde; C446481:aliskiren; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D005978:Glutathione; D015232:Dinoprostone; D007213:Indomethacin
keywords: Aliskiren; Cytokine; Indomethacin; Renin angiotensin aldestron system; Ulcer