Transforming growth factor alpha protection against drug-induced injury to the rat gastric mucosa in vivo.

Romano M, Polk WH, Awad JA, Arteaga CL, Nanney LB, Wargovich MJ, Kraus ER, Boland CR, Coffey RJ
J Clin Invest. 1992 90 (6): 2409-21

PMID: 1281834 · PMCID: PMC443397 · DOI:10.1172/JCI116132

This study was designed to determine whether transforming growth factor alpha (TGF alpha) protects rat gastric mucosa against ethanol- and aspirin-induced injury. Systemic administration of TGF alpha dose-dependently decreased 100% ethanol-induced gastric mucosal injury; a dose of 50 micrograms/kg delivered intraperitoneally 15 min before ethanol decreased macroscopic mucosal injury by > 90%. At the microscopic level, TGF alpha prevented deep gastric necrotic lesions and reduced disruption of surface epithelium. Pretreatment with orogastric TGF alpha (200 micrograms/kg) only partially (40%) decreased macroscopic ethanol damage. Intraperitoneal administration of TGF alpha at a dose of 10 micrograms/kg, which does not significantly inhibit gastric acid secretion, decreased aspirin-induced macroscopic damage by > 80%. TGF alpha protection does not seem to be mediated by prostaglandin, glutathione, or ornithine decarboxylase-related events, as evidenced by lack of influence of the inhibition of their production. Pretreatment with the sulfhydryl blocking agent N-ethylmaleimide partially abolished (40%) the protective effect of TGF alpha. In addition, systemic administration of TGF alpha resulted in a two-fold increase in tyrosine phosphorylation of phospholipase C-gamma 1 and in a time- and dose-dependent increase in levels of immunoreactive insoluble gastric mucin; these events occurred in a time frame consistent with their participation in the protective effect of TGF alpha.

MeSH Terms (21)

Animals Aspirin Dinoprostone Ethanol Ethylmaleimide Gastric Mucins Gastric Mucosa Image Processing, Computer-Assisted Indomethacin Microscopy, Electron, Scanning Necrosis Ornithine Decarboxylase Phosphorylation Phosphotyrosine Rats Rats, Sprague-Dawley Sulfhydryl Compounds Time Factors Transforming Growth Factor alpha Type C Phospholipases Tyrosine

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