Paraaminosalicylate blocks that ileal injury induced by phorbol myristate acetate.
Activation of neutrophils with the release of oxidant radicals has been implicated in the pathogenesis of gut injury in inflammatory bowel disease (IBD). The pathogenesis of gut injury in the multiple organ dysfunction syndrome associated with acute lung injury, although less focal, appears to be similar. Paraaminosalicylate (PAS) has been shown to be effective in treating IBD, most likely because of its ability to scavenge oxidant radicals. The present study was therefore designed to test the hypothesis that PAS attenuates the gut injury typically seen during systemic neutrophil activation by phorbol myristate acetate (PMA). We assessed gut injury by measuring the concentration ratio of lymph to plasma protein (CL/CP) at steady-state lymph flows in autoperfused cat ileum preparations. As expected, the CL/CP increased in animals given PMA (15 micrograms/kb; n = 6) compared with control animals (n = 5) (0.205 +/- 0.033 versus 0.118 +/- 0.004; p = 0.04) 0.04) and were accompanied by morphologic alterations. In contrast, the intravenous administration of PAS (100 mg/kg) to animals prior to PMA infusion (n = 5) yielded a CL/CP value indistinguishable from that in control animals (0.113 +/- 0.017 versus 0.118 +/- 0.004). Additional in vitro studies suggested that the protective effects of PAS were not the result of altered neutrophil margination, chemotaxis, or oxidant burst. Although PAS appeared to protect the ileum from PMA-induced microvascular injury, it had no protective effects on the lungs.
Overdahl
M C
MC
Department of Medicine, Ohio State University, Columbus.
Julian
M W
MW
Weisbrode
S E
SE
Davis
W B
WB
Dorinsky
P M
PM
D000208:Acute Disease; D010131:Aminosalicylic Acid / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis; D001798:Blood Proteins / Q000032:analysis; D002199:Capillary Permeability / Q000187:drug effects / Q000276:immunology; D002415:Cats; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000187:drug effects* / Q000276:immunology; D007077:Ileal Diseases / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007958:Leukocyte Count; D008196:Lymph / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology*; D011292:Premedication; D016897:Respiratory Burst / Q000187:drug effects / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate
D001798:Blood Proteins; D010131:Aminosalicylic Acid; D013755:Tetradecanoylphorbol Acetate