Effect of exogenous administration of transforming growth factor-beta and famotidine on the healing of duodenal ulcer under the impact of indomethacin.
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.
Pérez-Aisa
A
A
Service of Digestive Diseases, University Hospital, C/San Juan Bosco 15, 50009 Zaragoza, Spain. alanas@posta.unizar.es
Sopeña
F
F
Arceiz
E
E
Ortego
J
J
Sainz
R
R
Lanas
A
A
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*
D016212:Transforming Growth Factor beta; D015738:Famotidine; D007213:Indomethacin