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

M. Romano, W. H. Polk, J. A. Awad, C. L. Arteaga, L. B. Nanney, M. J. Wargovich, E. R. Kraus, C. R. Boland, R. J. Coffey

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102 Scopus citations

Abstract

This study was designed to determine whether transforming growth factor α (TGFα) protects rat gastric mucosa against ethanol- and aspirin-induced injury. Systemic administration of TGFα dose-dependently decreased 100% ethanol-induced gastric mucosal injury; a dose of 50 μg/kg delivered intraperitoneally 15 min before ethanol decreased macroscopic mucosal injury by > 90%. At the microscopic level, TGFα prevented deep gastric necrotic lesions and reduced disruption of surface epithelium. Pretreatment with orogastric TGFα (200 μg/kg) only partially (40%) decreased macroscopic ethanol damage. Intraperitoneal administration of TGFα at a dose of 10 μg/kg, which does not significantly inhibit gastric acid secretion, decreased aspirin-induced macroscopic damage by > 80%. TGFα 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 TGFα. In addition, systemic administration of TGFα 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 TGFα.

Original languageEnglish (US)
Pages (from-to)2409-2421
Number of pages13
JournalJournal of Clinical Investigation
Volume90
Issue number6
DOIs
StatePublished - Jan 1 1992

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Keywords

  • aspirin
  • ethanol
  • prostaglandin
  • sulfhydryl
  • transforming growth factor α

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Romano, M., Polk, W. H., Awad, J. A., Arteaga, C. L., Nanney, L. B., Wargovich, M. J., Kraus, E. R., Boland, C. R., & Coffey, R. J. (1992). Transforming growth factor α protection against drug-induced injury to the rat gastric mucosa in vivo. Journal of Clinical Investigation, 90(6), 2409-2421. https://doi.org/10.1172/JCI116132