Stimulation of mucosal glutathione and angiogenesis: new mechanisms of gastroprotection and ulcer healing by sucralfate.
BACKGROUND
Among the endogenous mediators (e.g., PG, SH) of gastroprotection, so far only PG was implicated in the mechanism of acute gastroprotection by sucralfate. Angiogenesis, which is stimulated by bFGF, is a recently recognized element in ulcer healing, and sucralfate binds bFGF in vitro and in vivo.


METHODS
In fasted rats the gastric mucosal concentration of GSH and protein SH was measured at 30, 60, 120, and 240 min after a single gastroprotective dose of sucralfate. In normally fed rats, angiogenesis was measured in the subcutaneous sponge assay 7 days after the implantation of sponges containing sucralfate and/or bFGF.


RESULTS
A gastroprotective dose of sucralfate time-dependently increased GSH concentration in the gastric mucosa. Sucralfate alone accelerated angiogenesis, which was significantly enhanced by combination with an ineffective dose of bFGF in the subcutaneous sponge assay. The same dose of sucralfate combined with an angiogenic dose of bFGF also resulted in synergistic stimulation (e.g., more than fivefold) of angiogenesis.


CONCLUSIONS
It appears that elevated mucosal GSH concentration may represent a new factor in the mechanism of acute gastroprotection by sucralfate, and stimulation of angiogenesis is one of the mechanisms of ulcer healing by sucralfate.
Sandor
Z
Z
Dept. of Pathology, University of California, Irvine, USA.
Nagata
M
M
Kusstatscher
S
S
Szabo
S
S
D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D005260:Female; D005346:Fibroblast Growth Factors / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000502:physiology*; D006097:Granulation Tissue / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D013392:Sucralfate / Q000627:therapeutic use*
D000897:Anti-Ulcer Agents; D013392:Sucralfate; D005346:Fibroblast Growth Factors; D005978:Glutathione