REDUCTION OF GASTROINTESTINAL INJURY IN ACUTE ENDOTOXIC-SHOCK BY FLURBIPROFEN NITROXYBUTYLESTER

Nitric oxide has been reported to have paradoxical effects in experime ntal endotoxic shock, contributing to the hemodynamic consequences of endotoxin administration, but apparently protecting the gastrointestin al mucosa. A novel class of nitric oxide-releasing nonsteroidal anti-i nflammatory drug (NSAID) derivatives has recently been described which exert anti-inflammatory activities but produce significantly less gas trointestinal injury than the parent nonsteroidal anti-inflammatory dr ugs 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-inflammator y drug, flurbiprofen, in an experimental model of endotoxic shock. Int ravenous administration of endotoxin from Salmonella typhosa to rats p retreated with flurbiprofen produced a profound decrease in systemic a rterial blood pressure, an increase in hematocrit and extensive gastri c and small intestinal damage. In rats pretreated with flurbiprofen 4- nitroxybutylester, endotoxin produced comparable changes in blood pres sure and hematocrit to those seen in rats treated with flurbiprofen; h owever, the severity of gastrointestinal damage was significantly redu ced. Gastric blood flow was profoundly decreased following endotoxin a dministration, but was significantly higher in rats pretreated with fl urbiprofen 4-nitroxybutylester than in rats pretreated with flurbiprof en. These results demonstrate that despite not affecting the acute sys temic effects of endotoxin administration, flurbiprofen 4-nitroxybutyl ester is capable of protecting the gastrointestinal mucosa from injury , possibly through preservation of mucosal blood flow.