prostaglandin-d2 and Stomach-Ulcer

Prostaglandin E(2) and D(2) (PGE(2) and PGD(2)) production and cyclooxygenase-2 (COX-2) expression during the resolution of acute and chronic gastric inflammatory lesions in Wistar rats have been investigated. Differences between ibuprofen, nonselective COX inhibitor, and rofecoxib, specific COX-2 inhibitor, on the development of the induced responses were also analysed. In an acute model, by instillation of HCL, the greatest injury was observed early with a rapid and progressive restoration. Maximal up-regulation of COX-2 protein was detected at 6 h and was accompanied by increase of PGE(2) synthesis but not PGD(2). Both drugs stimulated COX-2 expression in accordance to their capacity of inhibiting this enzymatic activity, driving to delay in the healing. In a chronic model, by acetic acid-induced gastric ulcers, COX-2 was expressed at 7 days and was also associated with PGE(2) increase. Ibuprofen and rofecoxib also augmented COX-2 protein and inhibited PGE(2) levels. However, PGD(2) production was augmented when none signal of COX-2 protein could be detected. Together, this study confirms the role played by COX-2 enzyme in the resolution of acute and chronic gastric inflammatory process, PGE(2) being the principal product. The antiinflammatory effect of nonsteroidal antiinflammatory drugs (NSAIDs) could be mediated not only through the inhibition of COX activity but also through the induction of antiinflammatory PGs production-such as PGD(2)-although further studies would be needed to clarify the mechanisms of this activity and the possible implicated processes.

Topics: Acetic Acid; Acute Disease; Animals; Chronic Disease; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Disease Models, Animal; Hydrochloric Acid; Ibuprofen; Lactones; Male; Membrane Proteins; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Stomach Ulcer; Sulfones

In the present study, the role of endogenous prostanoid synthesis in gastric mucosa in the healing of chronic gastric ulcers was investigated. Nineteen patients were divided into two groups in accordance with healing state after one month of treatment with cimetidine only: "healed group" and "unhealed group". Biopsy specimens taken from the mucosa around the ulceration (damaged gastric mucosa) and at a distance from the ulceration (normal gastric mucosa) at endoscopy prior to treatment were homogenized, and the mucosal prostanoid synthesis was determined using [14C]arachidonic acid. The mean value of prostaglandin E2 synthesis in the normal gastric mucosa of the healed group was 60% higher than in that of the unhealed group, but the difference was not significant. However, prostaglandin E2 synthesis in the damaged gastric mucosa of the healed group was 117% higher than in that of the unhealed group. The same tendency was observed for prostaglandin D2 and 6-keto prostaglandin F1 alpha synthesis as for prostaglandin E2. In our study it was demonstrated that there is a good correlation of prostaglandin synthesis in the damaged mucosa with healing of chronic gastric ulceration. Furthermore, our study indicated that prostaglandin synthesis, especially in damaged mucosa, might be important in the healing of gastric ulceration.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Autoradiography; Chronic Disease; Cimetidine; Dinoprostone; Female; Gastric Mucosa; Humans; Male; Middle Aged; Prostaglandin D2; Prostaglandins; Stomach Ulcer

Four kinds of prostaglandins (PGs), 6-keto-PGF1 alpha, PGF2 alpha, PGE2 and PGD2, in rat gastric mucosa were decreased at 1 or 6 h after oral administration of indomethacin (2 or 12 mg/kg). With 2 mg/kg of indomethacin, the PG levels had slightly recovered 6 h later. Gastric lesions were observed 6 h after administration of indomethacin (12 mg/kg), but not with 2 mg/kg. Omeprazole (20 mg/kg, i.p.) prevented ulcer formation caused by indomethacin, without improvement of the reduced gastric mucosal PG levels. PGD2 (0.5 mg/kg, p.o.) reduced indomethacin-induced gastric lesions and considerable amounts of PGD2 existed in the gastric mucosa. We conclude that H+ is a determining factor in the genesis of indomethacin-induced gastric lesions and persistent decreases in tissue PG levels also participate in ulcer formation.

Topics: Animals; Biomechanical Phenomena; Gastric Mucosa; Indomethacin; Male; Omeprazole; Prostaglandin D2; Prostaglandins; Rats; Rats, Inbred Strains; Stomach; Stomach Ulcer

We investigated the different effects of administration of high and low concentrations of ethanol (from 3% to 50%) on gastric mucosa in rats in relation to the changes in prostaglandin (PG) levels. Gastric lesions were induced by 50% ethanol, and all kinds of PGs were significantly decreased 1 h after administration, concomitantly. Thirty percent ethanol did not induce gastric lesions and had no effects on PG levels. Five percent ethanol significantly increased 6-keto-PGF1 alpha, PGF2 alpha, and PGE2 levels. Ten percent ethanol increased significantly PGD2 level. Premedication with sucralfate protected significantly gastric mucosa against 50% ethanol, and maintained PG levels, concomitantly. We also investigated the recovery time course of gastric lesions by 50% ethanol. Gastric lesions did not recover significantly after 24 h, recovered considerably after 48 h, and fully after 96 h. Levels of 6-keto-PGF1 alpha, PGF2 alpha, and PGE2 were fully recovered 24 h after exposure to 50% ethanol; however, a significant decrease in PGD2 level still was observed. PGD2 was recovered significantly after 48 h. These results indicate that different concentrations of ethanol induce different effects on gastric mucosal PGs, and that not only PGE2, but also other PGs, especially PGD2, might be linked with the genesis and recovery of gastric lesions by 50% ethanol.

Topics: Animals; Ethanol; Gastric Mucosa; Male; Prostaglandin D2; Prostaglandins; Rats; Rats, Inbred Strains; Stomach Ulcer; Sucralfate

We have observed that the contents of prostaglandin (PG) D2 and 6-keto-PGF1 alpha were five times higher than those of PGE2 and PGF2 alpha in rat gastric mucosa. In order to elucidate the role of PGs in the function of gastric mucosa, we studied the effect of hypoxia on the levels of PGs in relation to the degree of gastric mucosal lesions. 6-Keto-PGF1 alpha levels were significantly decreased only by severe and long-term hypoxia (10% O2, 18 hours) when severe ulcerative lesions were observed. PGE2 levels were significantly decreased even by mild and short-term hypoxia (13% O2, 4 hours) when slight ulcerative lesions were observed. PGF2 alpha and PGD2 levels were significantly decreased by mild and short-term hypoxia; however, there was no significant difference from the control group under severe and long-term hypoxia. These results suggest that each of the PGs plays a different role in the pathogenesis of acute gastric mucosal lesions induced by hypoxia.

Topics: Animals; Dinoprost; Dinoprostone; Epoprostenol; Gastric Mucosa; Hypoxia; Male; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Stomach Ulcer