Role of leukocytes in indomethacin-induced small bowel injury in the rat.
This study assesses the role of neutrophils in indomethacin-induced small bowel injury and determines the influence of intestinal pH on the magnitude of this injury. Rat jejunum was perfused via the lumen with buffer, and mucosal injury was assessed by blood-to-lumen clearance of 51Cr-EDTA and quantitative histology. Reduction in luminal pH from 7.4 to 6.0 in the presence of indomethacin (1.0 mg/ml) increased 51Cr-EDTA clearance from 2.0 +/- 0.1 to 6.5 +/- 0.3 microliter.min-1.g-1. Indomethacin caused a reduction in villus length, an increase in villus width, and an increase in lesion score. Depletion of neutrophils with antiserum largely prevented the increase in 51Cr-EDTA clearance and morphological changes. Intravenous indomethacin given at a dose to mimic therapeutic plasma levels (1 mg/kg iv) had no significant effect on 51Cr-EDTA clearance but caused similar morphological changes to those observed following intraluminal administration. The data suggest that neutrophils play a role in acute indomethacin injury and that the drug given intravenously can cause morphological changes without necessarily altering mucosal permeability to 51Cr-EDTA.
Chmaisse
H M
HM
School of Physiology and Pharmacology, University of New South Wales, Sydney, Australia.
Antoon
J S
JS
Kvietys
P R
PR
Grisham
M B
MB
Perry
M A
MA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004492:Edetic Acid / Q000493:pharmacokinetics; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology*; D007583:Jejunum / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D010477:Perfusion; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar
D004492:Edetic Acid; D007213:Indomethacin