Inhibition of arachidonic acid metabolism in colonic inflammation
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 inflammatory bowel disease.
- Research Organization:
- Smith Kline and French Labs., Philadelphia, PA
- OSTI ID:
- 5318751
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ACETIC ACID
ANIMALS
ARACHIDONIC ACID
BIOLOGICAL EFFECTS
BIOLOGICAL MODELS
BODY
CARBOXYLIC ACIDS
CHROMATOGRAPHY
DIGESTIVE SYSTEM
GASTROINTESTINAL TRACT
IMMUNOASSAY
IMMUNOLOGY
IN VIVO
INFLAMMATION
INHIBITION
INTESTINES
ISOTOPE APPLICATIONS
LARGE INTESTINE
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
METABOLISM
METABOLITES
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNOLOGY
RATS
RODENTS
SEPARATION PROCESSES
SYMPTOMS
TRACER TECHNIQUES
VERTEBRATES