Different molecular forms of basic fibroblast growth factor (bFGF) accelerate duodenal ulcer healing in rats.
Basic fibroblast growth factor is an angiogenic polypeptide that exhibits potent antiulcer activity without decreasing gastric acid or pepsin secretion. In this study, we investigated the effect of three acid-stable derivatives of human recombinant bFGF (hrbFGF) on the healing of chronic duodenal ulcer in rats. In Sprague-Dawley female rats, duodenal ulcers were induced by cysteamine-HCl. After laparotomy, rats were randomized to create six groups with homogeneously severe ulcers (perforated or penetrated into the liver or pancreas) and treated by gavage twice a day for 3 weeks with a) vehicle, b) cimetidine (10 mg/100 g), c) Ser78,96-hrbFGF (bioequivalent to rbFGF-CS23), d) CMC-hrbFGF, a carboxymethyl cysteine derivative of hrbFGF or e) PEG-hrbFGF, a polyethylene glycol derivative of hrbFGF. The peptides were administered at 100 ng/100 g. Autopsy was performed on the 21st day, and the ulcer size was measured. The ulcer sizes (mm2) were reduced from 10.3 +/- 1.8 in controls to 4.8 +/- 1.4* after cimetidine treatment and to 5.0 +/- 2.4, 4.2 +/- 1.1* and 0.5 +/- 0.2**, respectively, after administration of aforementioned hrbFGF derivatives (*P < .05; **P < .01 vs. vehicle group), which also significantly enhanced angiogenesis in the ulcer bed.


CONCLUSIONS
1) Oral administration of novel derivatives of hrbFGF accelerated the healing of cysteamine-induced chronic duodenal ulcer. 2) The PEG-hrbFGF derivative was more active than the other hrbFGF analogs. 3) The naturally occurring bFGF provides a good prototype to design new locally acting antiulcer drugs.
Kusstatscher
S
S
Chemical Pathology Research Division, Brigham & Women's Hospital, Boston, Massachusetts, USA.
Sandor
Z
Z
Szabo
S
S
Seddon
A
A
Böhlen
P
P
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004355:Drug Stability; D004381:Duodenal Ulcer / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007536:Isomerism; D008853:Microscopy; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D011092:Polyethylene Glycols; D002927:Cimetidine