Gastrointestinal damage induced by platelet-activating factor. Inhibition by the corticoid, dexamethasone.
Intravenous infusion of platelet-activating factor (PAF-acether) induces extensive vasocongestion and damage in the stomach and small intestine of the rat. The effect of pretreatment with the corticoid dexamethasone (2 mg/kg) on such gastrointestinal damage in the rat has now been investigated, using macroscopic observation and the release of acid phosphatase, as an enzyme marker of cell disruption. Administration of PAF-acether (100 ng/kg/min intravenously, for 10 min) induced focal, intense hyperemia and hemorrhage in all the regions of the gastrointestinal tract, with the exception of the distal colon. This damage was associated with an increase in the release of acid phosphatase into the lumen of the stomach, duodenum, jejunum, and ileum following incubation in vitro. Pretreatment with dexamethasone reduced the macroscopically apparent gastrointestinal damage following PAF-acether administration and abolished the intraluminal release of acid phosphatase. Dexamethasone also significantly suppressed the hemoconcentration, as determined by changes in platelet and erythrocyte count and hematocrit, 30 min after PAF-acether infusion. Thus, as in endotoxin shock, this glucocorticoid can reduce the gastrointestinal damage associated with PAF-acether administration.
Wallace
J L
JL
Department of Mediator Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, England.
Whittle
B J
BJ
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004906:Erythrocyte Count; D005753:Gastric Mucosa / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D010972:Platelet Activating Factor; D010976:Platelet Count; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains
D010972:Platelet Activating Factor; D003907:Dexamethasone; D000135:Acid Phosphatase