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

J Clin Invest. 1992 Dec;90(6):2409-21. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspirin / toxicity
  • Dinoprostone / metabolism
  • Ethanol / toxicity
  • Ethylmaleimide / pharmacology
  • Gastric Mucins / metabolism
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Image Processing, Computer-Assisted
  • Indomethacin / pharmacology
  • Microscopy, Electron, Scanning
  • Necrosis
  • Ornithine Decarboxylase / metabolism
  • Phosphorylation
  • Phosphotyrosine
  • Rats
  • Rats, Sprague-Dawley
  • Sulfhydryl Compounds / metabolism
  • Time Factors
  • Transforming Growth Factor alpha / pharmacology*
  • Type C Phospholipases / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism


  • Gastric Mucins
  • Sulfhydryl Compounds
  • Transforming Growth Factor alpha
  • Phosphotyrosine
  • Ethanol
  • Tyrosine
  • Type C Phospholipases
  • Ornithine Decarboxylase
  • Dinoprostone
  • Ethylmaleimide
  • Aspirin
  • Indomethacin