16-16-dimethylprostaglandin-e2 and Colitis

A standard colitic lesion was induced in male BKA mice by intrarectal administration of butyric acid (7.5%, 0.1 ml, 10 sec contact). Animals were killed after 5 h and the 'colitic score', increase in colonic tissue water ('oedema') and colonic tissue content of myeloperoxidase (MPO, a marker for neutrophils) were determined. Drug was administered intrarectally in 0.2 ml saline 20 min before colitis induction. In colitic animals given vehicle alone, all these parameters increased (P less than 0.05) compared to the non-colitic controls. In colitic animals given 16,16-dimethyl PGE2 (0.2-20000 micrograms/kg), colitic score was reduced (P less than 0.05) at all dose levels when compared with vehicle-treated colitic animals. The oedema and MPO showed a dose-related reduction (r = -0.895 and -0.904 respectively). In mouse colon 16,16-dimethyl PGE2 showed a protective action against butyric acid-induced colitic damage.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Butyrates; Butyric Acid; Colitis; Colon; Dose-Response Relationship, Drug; Intestinal Mucosa; Male; Mice; Peroxidase

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.

Topics: 16,16-Dimethylprostaglandin E2; Acute Disease; Animals; Arachidonic Acid; Arachidonic Acids; Colitis; Colon; Dinoprostone; Leukotrienes; Male; Peroxidase; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Trinitrobenzenesulfonic Acid

Topics: 16,16-Dimethylprostaglandin E2; Animals; Colitis; Prostaglandins E, Synthetic; Rats