title: Effect of exogenous administration of transforming growth factor-beta and famotidine on the healing of duodenal ulcer under the impact of indomethacin.
abstract: BACKGROUND
  Non-steroidal anti-inflammatory drugs delay ulcer healing and cause refractory peptic ulcers in humans.
  
  
  OBJECTIVE
  To study the effects of growth factors on experimental duodenal ulcer healing in indomethacin-treated rats.
  
  
  METHODS
  Duodenal ulcers were induced in male Wistar rats by the serosal application of 75% acetic acid for 10 s. Rats were then treated with indomethacin (2 mg/kg/day; s.c.), transforming growth factor beta (15 ng locally injected subserosally at the ulcer site) or famotidine (5 mg/kg/day; p.o.), vehicle or combinations of treatments. On day 5, 8 or 12, rats were sacrificed and the ulcer area planimetrically measured under a dissecting microscope. Macroscopic area, microscopic diameter, collagen content and mucosal regeneration were assessed in histological preparations. Gastric secretion was assessed also in the pylorus-ligated rat-model. Data expressed as median and ranges were analyzed by non-parametric test.
  
  
  RESULTS
  Indomethacin delayed ulcer healing but transforming growth factor-beta and famotidine improved ulcer healing and reversed the effects of indomethacin. Maximal differences were observed on day 8. Transforming growth factor-beta was associated with an increase in epithelial and granulation tissue cell proliferation. Famotidine induced a profound inhibition of gastric secretion and increased collagen secretion but it did not affect cell proliferation.
  
  
  CONCLUSIONS
  Transforming growth factor-beta and famotidine accelerate ulcer healing delayed by indomethacin.
authors.affiliation: Service of Digestive Diseases, University Hospital, C/San Juan Bosco 15, 50009 Zaragoza, Spain. alanas@posta.unizar.es
authors.forename: A
authors.initials: A
authors.lastname: Pérez-Aisa
authors.forename: F
authors.initials: F
authors.lastname: Sopeña
authors.forename: E
authors.initials: E
authors.lastname: Arceiz
authors.forename: J
authors.initials: J
authors.lastname: Ortego
authors.forename: R
authors.initials: R
authors.lastname: Sainz
authors.forename: A
authors.initials: A
authors.lastname: Lanas
mesh_terms: D000818:Animals; D004381:Duodenal Ulcer / Q000188:drug therapy* / Q000473:pathology; D015738:Famotidine / Q000627:therapeutic use*; D005744:Gastric Acid / Q000378:metabolism; D007213:Indomethacin / Q000009:adverse effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*
chemical_list: D016212:Transforming Growth Factor beta; D015738:Famotidine; D007213:Indomethacin