title: Preventive effects of geranylgeranylacetone on rat ethanol-induced gastritis.
abstract: OBJECTIVE
  To establish a rat ethanol gastritis model, we evaluated the effects of ethanol on gastric mucosa and studied the preventive effects of geranylgeranylacetone on ethanol-induced chronic gastritis.
  
  
  METHODS
  One hundred male Sprague-Dawley rats were randomly divided into 4 equal groups: normal control group, undergoing gastric perfusion of normal saline (NS) by gastrogavage; model control group and 2 model therapy groups that underwent gastric perfusion with ethanol (distillate spirits with 56% ethanol content) by gastrogavage for 4 wk. Low or high doses of geranylgeranylacetone were added 1 h before ethanol perfusion in the 2 model therapy groups, while the same amount of NS, instead of geranylgeranylacetone was used in that model control group. The rats were then sacrificed and stomachs were removed. The injury level of the gastric mucosa was observed by light and electron microscopy, and the levels of prostaglandin 2 (PGE₂), endothelin-1 (ET-1) and nitric oxide (NO) were measured by radioimmunoassay and the Griess method.
  
  
  RESULTS
  The gastric mucosal epidermal damage score (EDS; 4.5) and ulcer index (UI; 12.0) of the model control group were significantly higher than that of the normal control group (0 and 0 respectively, all P = 0.000). The gastric mucosal EDS and UI of the 2 model therapy groups (EDS: 2.5 and 2.0; UI: 3.5 and 3.0) were significantly lower than that of the model control group (all P < 0.01). There was no statistically significant difference between the low-dose and high-dose model therapy groups. The expression value of plasma ET-1 of the model control group was higher than that of the normal control group (P < 0.01) and the 2 model therapy groups (all P < 0.01). The expression values of gastric mucosal PGE₂ and serum NO of the model control group were lower than those of the normal control group (all P < 0.05) and the 2 model therapy groups (all P < 0.05). The thickness of the gastric mucous layerand the hexosamine content in the model control group were significantly lower than that in the normal control group (all P < 0.01) and the 2 model therapy groups (all P < 0.05). Scanning and transmission electron microscopy observation showed that in the model control group, the epithelial junctions were vague, the intercellular joints disappeared and damage of the intracellular organelles were significantly worse than those in the normal control group. However, in the 2 model therapy groups, damage to the intercellular joints and organelles was ameliorate relative to the model control group.
  
  
  CONCLUSIONS
  Administration of geranylgeranylacetone was correlated with a more favorable pattern of gastric mucosa damage after ethanol perfusion. The mechanism could be related to regulation of ET-1, NO and PGE₂.
authors.affiliation: Department of Emergency, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Ning
authors.forename: Guan-Bin
authors.initials: GB
authors.lastname: Lin
authors.forename: Feng
authors.initials: F
authors.lastname: Ji
authors.forename: Jia
authors.initials: J
authors.lastname: Xu
authors.forename: Najeeb
authors.initials: N
authors.lastname: Sharify
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D019610:Cytoprotection; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D019332:Endothelin-1 / Q000097:blood; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005756:Gastritis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009569:Nitric Oxide / Q000097:blood; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000097:blood / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000897:Anti-Ulcer Agents; D004224:Diterpenes; D019332:Endothelin-1; D009569:Nitric Oxide; D000431:Ethanol; D015232:Dinoprostone; C031049:geranylgeranylacetone