[Effect of exogenous administration of platelet-derived growth factor and epidermal growth factor on duodenal ulcer healing in rats treated with indomethacin].
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) delay peptic ulcer healing through mechanisms that are still not entirely understood. Growth factors play a significant role in healing.


OBJECTIVE
To evaluate whether exogenous administration of platelet-derived growth factor (PDGF) reverses the effect of indomethacin in experimental duodenal ulcers in rats and to define the potential mechanisms involved in this process.


METHODS
Duodenal ulcer was induced in male Wistar rats with acetic acid. The rats were then administered indomethacin (2 mg/kg/day), PDGF-BB (30 ng/100 g/day), epidermal growth factor (EGF) (50 /kg/day) or famotidine (positive control) or the possible combinations of these. Macroscopic area, reduction in microscopic diameter, epithelial and granulation tissue proliferation, collagen secretion by granulation tissue, and gastric acid secretion were analyzed.


RESULTS
Indomethacin delayed duodenal ulcer healing by decreasing cellular proliferation and inhibiting collagen secretion. PDGF and EGF accelerated healing and reversed the effects of indomethacin. The mechanisms involved were associated with an increase in collagen proliferation and secretion without affecting gastric acid secretion. Famotidine also accelerated healing and reversed the effect of indomethacin, and these effects were associated with a marked inhibition of gastric acid secretion and increase in collagen secretion by granulation tissue.


CONCLUSIONS
Exogenous administration of PDGF and EGF accelerated healing and reversed the harmful effects of indomethacin in an experimental model of duodenal ulcer.
Pérez Aisa
A
A
Servicio de Aparato Digestivo. Hospital Clínico Universitario. Zaragoza. Spain.
Sopeña Biarge
F
F
Arceiz Gonzalo
E
E
Sainz Samitier
R
R
Ortego Díez De Retana
J
J
Lanas Arbeloa
A
A
D019342:Acetic Acid; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015738:Famotidine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D010982:Platelet-Derived Growth Factor; D015738:Famotidine; D004815:Epidermal Growth Factor; D019342:Acetic Acid; D007213:Indomethacin