Epidermal growth factor in the gastroprotective and ulcer-healing actions of sucralfate in rats.
Sucralfate exhibits gastroprotective properties in laboratory animals and enhances the healing of chronic gastroduodenal ulcers, but the mechanisms of these actions have not been entirely elucidated. The present study was designed to determine whether or not epidermal growth factor (EGF), which also has gastroprotective and ulcer-healing properties, contributes to the action of sucralfate in rat stomach. It was confirmed that sucralfate, like 16,16-dimethyl prostaglandin E2, protects the gastric mucosa against ethanol damage and increases mucosal generation of prostaglandins. Removal of the endogenous source of EGF (sialoadenectomy) did not abolish the protective and prostaglandin-stimulating effects of sucralfate. Exogenous EGF and 16,16-dimethyl prostaglandin E2 were also protective in rats with intact and removed salivary glands. Sucralfate, like EGF, enhanced the healing of chronic gastric and duodenal ulcerations induced by serosal application of acetic acid. Sucralfate was found to bind EGF in a pH-dependent manner and to accumulate it in ulcer areas. Thus, the peptide is available locally in high concentrations to accelerate tissue repair and the healing process in ulcerated mucosa. The ulcer-healing effects of sucralfate were reduced with sialoadenectomy and partially restored with oral administration of EGF. It was concluded that EGF is not essential for the gastroprotection induced by sucralfate, but seems to play an important role in the ulcer-healing action of this drug.
Konturek
S J
SJ
Institute of Physiology, Academy of Medicine, Krakow, Poland.
Brozozowski
T
T
Bielanski
W
W
Warzecha
Z
Z
Drozdowicz
D
D
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000085:Acetates / Q000633:toxicity; D019342:Acetic Acid; D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D015232:Dinoprostone / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000502:physiology*; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D010437:Peptic Ulcer / Q000188:drug therapy / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013363:Submandibular Gland / Q000601:surgery; D013392:Sucralfate / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
D000085:Acetates; D000431:Ethanol; D013392:Sucralfate; D004815:Epidermal Growth Factor; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2; D019342:Acetic Acid