Inhibition of arachidonic acid metabolism in colonic inflammation
1986
The authors have previously identified a lipoxygenase product profile in the acetic acid-induced model of colonic inflammation in the rat and have demonstrated utility of this model in evaluating inhibitors of arachidonic acid (AA) metabolism under in vitro conditions. They now demonstrate efficacy of an inhibitor of AA metabolism in this model under in vivo conditions. Male rats were pretreated with either nordihydroguaiaretic acid (NDGA) (50 mg/kg, p.o.) or vehicle for 3 consecutive days prior to induction of colonic inflammation with intraluminal administration of 2 mls of 5% acetic acid. After sacrifice, colonic mucosa was removed and incubated in the presence and absence of Ca/sup 2 +/ ionophore, A23187 (2 ..mu..M) for 5 min at 37/sup 0/C. Production of AA metabolites (LTB/sub 4/, 5-HETE, PGE/sub 2/, TxB/sub 2/) was determined by high pressure liquid chromatography and radioimmunoassay. NDGA treatment caused a significant inhibition of metabolite production (LTB/sub 4/, 5-HETE, PGE/sub 2/, TxB/sub 2/) compared to vehicle controls. This inhibition was evident in both ionophore-stimulated and non-stimulated samples. These results show that intestinal AA metabolism can be inhibited by in vivo drug administration and further suggest that this animal model may provide a simple means for evaluating potential therapies for inflammatorymore » bowel disease.« less
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