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

Marco Romano, William H. Polk, Joseph A. Awad, Carlos L. Arteaga, Lillian B. Nanney, Michael J Wargovich, Eugene R. Kraus, C. Richard Boland, Robert J. Coffey

Research output: Contribution to journalArticle

101 Citations (Scopus)

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
StatePublished - Dec 1992
Externally publishedYes

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Transforming Growth Factors
Gastric Mucosa
Wounds and Injuries
Pharmaceutical Preparations
Ethanol
Aspirin
Stomach
Gastric Mucins
Phospholipase C gamma
Ethylmaleimide
Ornithine Decarboxylase
Gastric Acid
Prostaglandins
Glutathione
Tyrosine
Epithelium
Phosphorylation

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., ... Coffey, R. J. (1992). Transforming growth factor a protection against drug-induced injury to the rat gastric mucosa in vivo. Journal of Clinical Investigation, 90(6), 2409-2421.

Transforming growth factor a protection against drug-induced injury to the rat gastric mucosa in vivo. / Romano, Marco; Polk, William H.; Awad, Joseph A.; Arteaga, Carlos L.; Nanney, Lillian B.; Wargovich, Michael J; Kraus, Eugene R.; Boland, C. Richard; Coffey, Robert J.

In: Journal of Clinical Investigation, Vol. 90, No. 6, 12.1992, p. 2409-2421.

Research output: Contribution to journalArticle

Romano, M, Polk, WH, Awad, JA, Arteaga, CL, Nanney, LB, Wargovich, MJ, Kraus, ER, Boland, CR & Coffey, RJ 1992, 'Transforming growth factor a protection against drug-induced injury to the rat gastric mucosa in vivo', Journal of Clinical Investigation, vol. 90, no. 6, pp. 2409-2421.
Romano, Marco ; Polk, William H. ; Awad, Joseph A. ; Arteaga, Carlos L. ; Nanney, Lillian B. ; Wargovich, Michael J ; Kraus, Eugene R. ; Boland, C. Richard ; Coffey, Robert J. / Transforming growth factor a protection against drug-induced injury to the rat gastric mucosa in vivo. In: Journal of Clinical Investigation. 1992 ; Vol. 90, No. 6. pp. 2409-2421.
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