16-16-dimethylprostaglandin-e and Necrosis

A mechanism of cytoprotection by 16,16-dimethylprostaglandin E2 (16,16-dimethyl-PGE2) was investigated in rats with respect to possible roles of the gastric juice and the mucus gel layer. 16,16-Dimethyl-PGE2 significantly increased the volume of gastric juice and mucus thickness. In a gastric juice-emptied stomach, 16,16-dimethyl-PGE2 protected the gastric mucosa against 30% ethanol, but not against 40% ethanol. Moreover, this agent did not show any cytoprotective action even against 30% ethanol when both gastric juice and mucus gel were removed. In this situation there was no histological change in the depth of injury, whether 16,16-dimethyl-PGE2 was given as pretreatment or not. These results suggest that there are two mechanisms that may play major roles in the cytoprotection of the gastric mucosa by 16,16-dimethyl-PGE2: (a) dilution of necrotizing agents by increased gastric juice and (b) thickening of the mucus gel layer.

Topics: Animals; Ethanol; Gastric Juice; Gastric Mucosa; Male; Microscopy, Electron, Scanning; Necrosis; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains

16,16-Dimethyl prostaglandin E2, a known cytoprotective agent, was examined for its ability to protect the liver against complement-mediated necrosis induced by an intravenous injection of a monoclonal antibody against a rat liver-specific antigen in rats. The hepatic injury induced by the antibody was characterized by (a) rapid development of numerous massive hemorrhagic foci of necrotic liver cells, (b) marked increases in serum liver enzyme activities and (c) pronounced reduction in the CH50 level, presumably as a result of complement consumption in the liver. Pretreatment with 16,16-dimethyl prostaglandin E2 at intraperitoneal doses of 20 and 100 micrograms/kg suppressed the hepatic injury, as evidenced by markedly mitigated liver-cell necrosis and much smaller increases in the serum-enzyme activities compared with the values in diseased control animals. The prostaglandin analogue failed to prevent serum complement consumption in response to the antibody injection or affect the CH50 level at the preinjury stage, indicating that neither complement inactivation nor interference with the antigen-antibody reaction was involved in the hepatic protection. The hepatoprotective doses of 16,16-dimethyl prostaglandin E2 produced a significant increase in liver cyclic AMP content in a dose-related manner. In addition, intravenous dibutyryl cyclic AMP at 3 and 10 mg/kg dose-dependently prevented histological and biochemical changes in the hepatic damage without altering the rate of reduction in serum complement activity. Like 16,16-dimethyl prostaglandin E2, dibutyryl cyclic AMP did not affect the preinjury CH50 level.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bucladesine; Complement System Proteins; Cyclic AMP; Liver; Male; Necrosis; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains

The role of increased prostaglandin production and the effects of exogenous prostaglandins on inflammation of colitis are not established. We administered intramuscular 16,16-dimethyl prostaglandin E2 (DiM-PGE2) and indomethacin to rabbits with formalin immune-complex colitis and measured leukotriene B4 (LTB4), prostaglandin E2 (PGE2) and severity of inflammation. DiM-PGE2 (100 micrograms/kg/BID) reduced LTB4 production (from 401 +/- 108 to 216 +/- 58 pg/ml) and infiltration of neutrophils, mucosal necrosis, inflammatory exudate and edema (all P less than 0.05). Other studies determined that parenteral DiM-PGE2 did not reduce the initial chemical damage induced by formalin, suggesting that cytoprotection of chemical insult was not the mechanism of suppressed inflammation in the immune colitis model. Indomethacin (10 mg/kg/d) reduced endogenous PGE2 by 80%, but did not reduce leukotriene production or inflammation. Exogenous prostaglandins cause a dose-dependent suppression of inflammation in experimental colitis, by a mechanism other than cytoprotection of chemical-induced mucosal injury.

Topics: Animals; Colitis; Colon; Dinoprostone; Dose-Response Relationship, Drug; Indomethacin; Leukotriene B4; Male; Necrosis; Prostaglandins E, Synthetic; Rabbits