Treatment with 16,16'-dimethyl prostaglandin E2 before and after induction of colitis with trinitrobenzenesulfonic acid in rats decreases inflammation.
Colitis was induced in rats by intrarectal administration of trinitrobenzene sulfonic acid (80 mg/kg, in 30% ethanol). An acute inflammation with ulcers and neutrophil infiltration developed that evolved into a chronic inflammation and luminal narrowing with attendant smooth muscle hypertrophy. We assessed the effects of 16,16-dimethyl prostaglandin E2, administered either before or after trinitrobenzene sulfonic acid, on the development of inflammation. Inflammation was assessed by gross appearance using a grading scale (0-4) and by histology. The number of neutrophils present in inflamed colonic tissue was quantitated by the myeloperoxidase assay. The production of lipoxygenase products was monitored by incubation of colonic specimens with [14C]arachidonic acid and separation of the products by thin-layer chromatography and high-pressure liquid chromatography. Levels of leukotriene B4 were measured in tissue extracts by high-pressure liquid chromatography and ultraviolet absorbance. Eicosanoid production was also assayed by incubating colonic specimens and assaying the media for prostaglandin E2, leukotriene B4, and leukotriene C4 by radioimmunoassay. Trinitrobenzene sulfonic acid treatment resulted in a greatly increased amount of leukotriene B4 in the media. Treatment with 16,16-dimethyl prostaglandin E2 before administration of trinitrobenzene sulfonic acid resulted in a lower inflammation index, lower myeloperoxidase activity, and decreased production of leukotriene B4. Administration of 16,16-dimethyl prostaglandin E2 24 h after administration of trinitrobenzene sulfonic acid was also effective in reducing the inflammatory response. Treatment with 16,16-dimethyl prostaglandin E2 also prevented the development of long-term architectural changes 3 wk after administration of trinitrobenzene sulfonic acid. Rectal administration of dimethyl prostaglandin E2 also diminished the colitis induced by direct injection of trinitrobenzene sulfonic acid into the colonic wall.
Allgayer
H
H
Department of Medicine, Jewish Hospital of St. Louis, Washington University School of Medicine, Missouri.
Deschryver
K
K
Stenson
W F
WF
D015064:16,16-Dimethylprostaglandin E2 / Q000627:therapeutic use*; D000208:Acute Disease; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D015232:Dinoprostone / Q000096:biosynthesis; D015289:Leukotrienes / Q000096:biosynthesis; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011459:Prostaglandins E, Synthetic / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D014302:Trinitrobenzenesulfonic Acid
D001095:Arachidonic Acids; D015289:Leukotrienes; D011459:Prostaglandins E, Synthetic; D016718:Arachidonic Acid; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2