Reduction of gastrointestinal injury in acute endotoxic shock by flurbiprofen nitroxybutylester

Eur J Pharmacol. 1995 Jun 23;280(1):63-8. doi: 10.1016/0014-2999(95)00184-m.


Nitric oxide has been reported to have paradoxical effects in experimental endotoxic shock, contributing to the hemodynamic consequences of endotoxin administration, but apparently protecting the gastrointestinal mucosa. A novel class of nitric oxide-releasing nonsteroidal anti-inflammatory drug (NSAID) derivatives has recently been described which exert anti-inflammatory activities but produce significantly less gastrointestinal injury than the parent nonsteroidal anti-inflammatory drugs from which they are derived. Thus, the present study was performed to determine the effects of one of these derivatives, flurbiprofen 4-nitroxybutylester, compared to the native nonsteroidal anti-inflammatory drug, flurbiprofen, in an experimental model of endotoxic shock. Intravenous administration of endotoxin from Salmonella typhosa to rats pretreated with flurbiprofen produced a profound decrease in systemic arterial blood pressure, an increase in hematocrit and extensive gastric and small intestinal damage. In rats pretreated with flurbiprofen 4-nitroxybutylester, endotoxin produced comparable changes in blood pressure and hematocrit to those seen in rats treated with flurbiprofen; however, the severity of gastrointestinal damage was significantly reduced. Gastric blood flow was profoundly decreased following endotoxin administration, but was significantly higher in rats pretreated with flurbiprofen 4-nitroxybutylester than in rats pretreated with flurbiprofen. These results demonstrate that despite not affecting the acute systemic effects of endotoxin administration, flurbiprofen 4-nitroxybutylester is capable of protecting the gastrointestinal mucosa from injury, possibly through preservation of mucosal blood flow.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Blood Pressure / drug effects
  • Flurbiprofen / therapeutic use
  • Gastric Mucosa / drug effects
  • Gastrointestinal Diseases / chemically induced
  • Gastrointestinal Diseases / prevention & control*
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / prevention & control
  • Lipopolysaccharides / toxicity
  • Male
  • Nitric Oxide / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Salmonella typhi
  • Shock, Septic / complications*
  • Shock, Septic / drug therapy*
  • Stomach / blood supply


  • Anti-Inflammatory Agents, Non-Steroidal
  • Lipopolysaccharides
  • Nitric Oxide
  • Flurbiprofen