title: 15-PGDH inhibitors: the antiulcer effects of carbenoxolone, pioglitazone and verapamil in indomethacin induced peptic ulcer rats.
abstract: OBJECTIVE
  15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the enzyme responsible for prostaglandins (PGs) metabolism. PGs have an important role in the protection of stomach mucosa against destructive stimuli. The aim of the present study is to investigate the inhibitory effect of carbenoxolone, pioglitazone and verapamil on 15-PGDH enzyme.
  
  
  METHODS
  The experiments were carried out in the Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt from May 2011 to August 2011. Adult male albino rats were fasted for 18 hours before administration of high dose of indomethacin (30 mg/kg, p.o.), except for the negative control group which received saline only, followed by pyloric ligation to induce acute gastric ulcers. The rats were pretreated orally with saline, pioglitazone (20 mg/kg), verapamil (25 mg/kg), carbenoxolone (30 mg/kg) or their combinations 30 minutes before indomethacin. The rats were sacrificed after four hours of pyloric ligation. The effects of the previous treatments on the ulcer index (Ui), the microscopic appearance of gastric mucosa, the gastric acid output, the gastric barrier mucus content, and 15-PGDH enzyme activity were determined.
  
  
  RESULTS
  Indomethacin resulted in severe ulceration and increased gastric acid output (p < 0.05) compared to negative control. The rats pretreated with carbenoxolone, pioglitazone, verapamil had reduced ulcer index, gastric acid output and 15-PGDH activity (p < 0.05) compared to either indomethacin group or the negative control group. Individual treatments with carbenoxolone, pioglitazone or verapamil increased gastric barrier mucus (p < 0.05) compared to either indomethacin group or the negative control group. The combinations of verapamil with either carbenoxolone or pioglitazone caused further reduction in ulcer index, gastric acid output and 15-PGDH activity (p < 0.05), while causing further increase in gastric barrier mucus (p < 0.05) compared to their respective individual treatment group.
  
  
  CONCLUSIONS
  The antiulcer properties of pioglitazone and verapamil are, in part, consequences of their inhibitory effect on the enzyme 15-PGDH, responsible for PGs degradation, and the resultant prolongation of PGE2 biological activity in rat stomach mucosa.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt. fouda77@hotmail.com  
authors.forename: Y M
authors.initials: YM
authors.lastname: Moustafa
authors.forename: M F
authors.initials: MF
authors.lastname: El-Azab
authors.forename: A
authors.initials: A
authors.lastname: Fouda
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D002229:Carbenoxolone / Q000494:pharmacology / Q000627:therapeutic use*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007213:Indomethacin; D008297:Male; D009093:Mucus / Q000378:metabolism; D010437:Peptic Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077205:Pioglitazone; D051381:Rats; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000897:Anti-Ulcer Agents; D045162:Thiazolidinediones; D014700:Verapamil; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D002229:Carbenoxolone; D000077205:Pioglitazone; D007213:Indomethacin