title: Reduction of gastrointestinal injury in acute endotoxic shock by flurbiprofen nitroxybutylester.
abstract: 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.
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D005480:Flurbiprofen / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000187:drug effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012485:Salmonella typhi; D012772:Shock, Septic / Q000150:complications* / Q000188:drug therapy*; D013270:Stomach / Q000098:blood supply
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D005480:Flurbiprofen