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Misoprostol but not antacid prevents endotoxin-induced gastric mucosal injury

Role of tumor necrosis factor—Alpha

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Abstract

Many of the complications of septic shock are believed to be a consequence of elevated circulating levels of tumor necrosis factor (TNF), which is an important mediator of tissue injury. Prostaglandins (PGs) of the E series have recently been reported to inhibit TNF productionin vitro. We investigated thein vivo effect of misoprostol, a PGE1 analog, on endotoxin-induced gastric mucosal injury and TNF production. For the gastric mucosal injury studies, groups of animals were pretreated with intragastric misoprostol (100 and 200 μg/kg) or with antacid (2 ml/animal of Maalox Plus) 30 min prior to a challenge with intravenousE. coli lipopolysaccharide (LPS) at 5.0 mg/kg. Stomachs were examined 3 hr after LPS. Systemic endotoxin alone induced microscopic edema, vascular congestion, and polymorphonuclear (PMN) infiltration of the gastric mucosa. Pretreatment with misoprostol, but not with antacid, significantly and dose-dependently reduced the gastric mucosal injury. For the TNF studies, groups of rats were given either misoprostol (100 or 200 μg/kg, intragastric), or saline 1 hr prior to LPS challenge. Serum samples were obtained 1.5 hr after LPS challenge. Misoprostol dose-dependently and significantly (P<0.01) inhibited TNF activity. We conclude that misoprostol is a potent inhibitor of TNF systemic production and inhibits the gastric mucosal injury induced by endotoxemia. These studies suggest a potentially important therapeutic role for misoprostol in inflammatory diseases in which TNF exerts a contributory role.

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Authors and Affiliations

  1. Department of Medicine, Section of Gastroenterology, Tulane University School of Medicine, 1430 Tulane Avenue, 70112, New Orleans, Loursiana

    Mahendra Mahatma MD,  Naurang Agrawal MD, Esam Z. Dajani PhD, Steve Nelson MD, Chester nakamura BS & John Sitton BS

  2. G.D. Searle and Co., Chicago, Illinois

    Mahendra Mahatma MD,  Naurang Agrawal MD, Esam Z. Dajani PhD, Steve Nelson MD, Chester nakamura BS & John Sitton BS

  3. Department of Medicine, Section of Pulmonary and Critical Care, LSU Medical Center, New Orleans, Louisiana

    Mahendra Mahatma MD,  Naurang Agrawal MD, Esam Z. Dajani PhD, Steve Nelson MD, Chester nakamura BS & John Sitton BS

  4. Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana

    Mahendra Mahatma MD,  Naurang Agrawal MD, Esam Z. Dajani PhD, Steve Nelson MD, Chester nakamura BS & John Sitton BS

Authors
  1. Mahendra Mahatma MD
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  2. Naurang Agrawal MD
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  3. Esam Z. Dajani PhD
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  4. Steve Nelson MD
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  5. Chester nakamura BS
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  6. John Sitton BS
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Additional information

The study was funded by the Section of Gastroenterology, Department of Medicine, Tulane University.

Preliminary communication of this work was recently presented in abstract form: Mahatma M, Yagel, RV, Sitton J, Sbeiti M, Hoda, Nelson S, Agrawal N: Prevention of endotoxin-induced gastric injury by misoprostol. J Am Coll Gastroenteral85:1237, 1990.

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Mahatma, M., Agrawal, N., Dajani, E.Z. et al. Misoprostol but not antacid prevents endotoxin-induced gastric mucosal injury. Digest Dis Sci 36, 1562–1568 (1991). https://doi.org/10.1007/BF01296398

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  • DOI: https://doi.org/10.1007/BF01296398

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