title: Inhibition of neutrophil activation by ranitidine contributes to prevent stress-induced gastric mucosal injury in rats.
abstract: OBJECTIVE
  Activated neutrophils play a critical role in stress-induced gastric mucosal injury. We investigated the effect of ranitidine, an H2-receptor antagonist, on neutrophil activation in vitro and in rats with stress-induced gastric mucosal injury.
  
  
  METHODS
  Prospective, randomized, blinded, controlled study.
  
  
  METHODS
  Research laboratory at a university medical center.
  
  
  METHODS
  Effects of ranitidine on neutrophil elastase release, production of O2-, intracellular calcium concentration and expression of adhesion molecules CD11b and CD18 were examined in human neutrophils in vitro. The effect of ranitidine (30 mg/kg iv) on the development of gastric mucosal injury, neutrophil accumulation, and lipid peroxidation was investigated in male Wistar rats subjected to water-immersion restraint stress.
  
  
  RESULTS
  Ranitidine inhibited the release of neutrophil elastase as well as the production of O2-, the increase in the concentrations of intracellular calcium, a second messenger of neutrophil activation, and increases in CD11b and CD18 expression, in activated neutrophils. Ranitidine did not affect the expression of E-selectin on endothelial cells in vitro. Ranitidine significantly inhibited gastric accumulation of neutrophils and gastric mucosal lipid peroxidation in rats subjected to stress. Although oral administration of acid reversed the preventive effect of pirenzepine, an anti-cholinergic drug that inhibits gastric acid secretion, it did not affect the preventive effect of ranitidine. Leukocytopenia produced effects similar to those of ranitidine in animals subjected to stress.
  
  
  CONCLUSIONS
  Inhibition of neutrophil activation and gastric acid secretion by ranitidine might contribute to reduce stress-induced gastric mucosal injury.
authors.affiliation: Department of Laboratory Medicine, Kumamoto University School of Medicine, Japan. whynot@kaiju.medic.kumamoto-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Okajima
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Uchiba
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006851:Hydrochloric Acid / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D007970:Leukopenia; D015227:Lipid Peroxidation; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects*; D010890:Pirenzepine / Q000494:pharmacology; D011446:Prospective Studies; D011897:Random Allocation; D011899:Ranitidine / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013272:Stomach Diseases / Q000209:etiology / Q000517:prevention & control; D013312:Stress, Physiological / Q000150:complications*; D013997:Time Factors
chemical_list: D019040:E-Selectin; D006635:Histamine H2 Antagonists; D010890:Pirenzepine; D011899:Ranitidine; D006851:Hydrochloric Acid; D002118:Calcium