Possible mechanism of gastric mucosal protection by epidermal growth factor in rats.
The mechanism of the protection by human epidermal growth factor (hEGF) against the gastric mucosal lesions induced by acidified ethanol was studied in rats. At different times following the subcutaneous administration of hEGF (30 micrograms/kg), intragastric acidified ethanol (EtOH: 0.125 M HC1 = 50:50 v/v%) was administered to induce an experimental gastric mucosal lesion. Mean length of the lesion in the gastric mucosa was used as a lesion index. Extravasation of intravenously injected Evans blue into the gastric wall and gastric contents was used as an indicator of vascular permeability. Pretreatment with hEGF decreased both the gastric mucosal lesions and the increase of vascular permeability caused by acidified ethanol with similar time profiles relative to pretreatment with hEGF. Maximal protective actions of hEGF occurred about 10 to 30 min after the observed peak plasma concentration of hEGF. Indomethacin and N-ethylmaleimide, but not iodoacetamide, blocked the protective action of hEGF, indicating that endogenous prostaglandins and/or sulfhydryls may participate in the protective action of hEGF. The content of endogenous nonprotein sulfhydryls in the gastric mucosa decreased markedly after acidified ethanol. However, pretreated hEGF did not restore the sulfhydryl contents. Thus, it seemed that endogenous prostaglandins, but not sulfhydryls, are the probable mediators for protection against gastric mucosal injury caused by acidified ethanol.
Amagase
H
H
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
Murakami
T
T
Misaki
M
M
Higashi
Y
Y
Hashimoto
K
K
Fuwa
T
T
Yata
N
N
D000818:Animals; D000897:Anti-Ulcer Agents; D002199:Capillary Permeability / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000097:blood / Q000494:pharmacology*; D005033:Ethylmaleimide / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007460:Iodoacetamide / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013997:Time Factors
D000897:Anti-Ulcer Agents; D011453:Prostaglandins; D011994:Recombinant Proteins; D013438:Sulfhydryl Compounds; D004815:Epidermal Growth Factor; D005033:Ethylmaleimide; D007213:Indomethacin; D007460:Iodoacetamide