thromboxane-b2 and Gastritis

Neutrophil infiltration mediated by TNF-alpha is associated with various types of gastric injury, whereas PGs play a crucial role in gastric defense. We examined roles of two isoforms of cyclooxygenase (COX) and PGE2 in Helicobacter pylori-induced gastritis in mice. Mice infected with H. pylori were given selective COX-1 inhibitor SC-560 (10 mg/kg), selective COX-2 inhibitor NS-398 (10 mg/kg), or nonselective COX inhibitor indomethacin (2 mg/kg) with or without 16,16-dimethyl PGE2 for 1 wk. H. pylori infection increased levels of mRNA for COX-1 and -2 in gastric tissue by 1.2-fold and 3.3-fold, respectively, accompanied by a significant increase in PGE2 production by gastric tissue. H. pylori infection significantly elevated MPO activity, a marker of neutrophil infiltration, and epithelial cell apoptosis in the stomach. SC-560 augmented MPO activity and epithelial cell apoptosis with associated reduction in PGE2 production, whereas NS-398 had the same effects without affecting PGE2 production. Inhibition of both COX-1 and -2 by indomethacin or concurrent treatment with SC-560 and NS-398 resulted in a stronger increase in MPO activity and apoptosis than inhibition of either COX-1 or -2 alone. H. pylori infection elevated TNF-alpha mRNA expression in the stomach, which was further increased by indomethacin. Effects of COX inhibitors on neutrophil infiltration, apoptosis, and TNF-alpha expression in H. pylori-infected mice were abolished by exogenous 16,16-dimethyl PGE2. In conclusion, PGE2 derived from either COX-1 or -2 is involved in regulation of gastric mucosal inflammation and contributes to maintenance of mucosal integrity during H. pylori infection via inhibition of TNF-alpha expression.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Blotting, Western; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Epithelial Cells; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Indomethacin; Isoenzymes; Membrane Proteins; Mice; Mice, Inbred C57BL; Prostaglandin-Endoperoxide Synthases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thromboxane B2; Tumor Necrosis Factor-alpha

The PG content were determined in 62 cases with peptic ulcer and erosive gastritis before and after the treatment of Chinese herbal drugs. The value of PGE2,PGF1 alpha, 6-keto-PGF1 alpha and TXB2 were 96.25 +/- 28.51, 14.24 +/- 13.26, 10.72 +/- 9.14 and 16.51 +/- 12.24 pg/mg respectively before the treatment and were 121.42 +/- 30.02, 18.59 +/- 18.40, 18.79 +/- 12.61, 8.29 +/- 6.27 pg/mg respectively after the treatment. 6-keto-PGF1 alpha was significantly increased (P < 0.01), TXB2 was decreased (P < 0.01), but there were no significant changes in PGE2 and PGF1 alpha. Experimental study also showed that Chinese Herbal drugs played an important role in protecting indomethacine induced ulcer rats.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Animals; Dinoprostone; Drugs, Chinese Herbal; Female; Gastric Mucosa; Gastritis; Humans; Male; Middle Aged; Peptic Ulcer; Rats; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Chronic Disease; Female; Gastric Juice; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Peptic Ulcer; Prostaglandins; Thromboxane B2

Colonisation with Helicobacter pylori may influence susceptibility to gastroduodenal injury and ulceration in patients taking non-steroidal anti-inflammatory drugs (NSAIDs). The aim of this study was to determine if Helicobacter pylori colonisation altered eicosanoid synthesis by gastric mucosa in these patients. Sixty five patients with long-standing NSAID intake and 23 control subjects underwent endoscopy. In vitro gastric antral biopsies were stimulated by vortex mixing and eicosanoid measurements determined by radioimmunoassay. Helicobacter pylori colonisation was determined by a CLO test (a gel based rapid urease test) and histological assessment. Median prostaglandin E2 synthesis by gastric mucosa was 61.0 (interquartile range: 19.2-73.1) pg/mg in control subjects colonised with Helicobacter pylori compared with 46.5 (23.3-65.5) pg/mg in Helicobacter pylori negative subjects. This was not significantly different. Treatment with NSAIDs was associated with a significant difference (p < 0.001) in prostaglandin E2 (PGE2) synthesis between those colonised with Helicobacter pylori (37.5(22.0-77.3) pg/mg) compared with patients not infected (12.6(7.0-19.3) pg/mg). Values in patients taking NSAIDs who were colonised were not different from control subjects. Synthesis of PGE2 was strongly associated with type B (chronic active), but not type C (chemical) gastritis. Dyspeptic symptoms were more common in subject colonised with Helicobacter pylori (p < 0.002) and were associated with higher PGE2 synthesis. In patients taking NSAIDs Helicobacter pylori colonisation removes rather then enhances depression of PGE2 synthesis associated with NSAIDs and may promote dyspepsia associated with ulcers and prevent superficial mucosal injury.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Dinoprostone; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Smoking; Stomach Ulcer; Thromboxane B2

Many organs have the capacity to form prostanoids. Under pathophysiological conditions the biosynthesis of TXB2 and 6-oxo-PGF1 alpha is markedly increased in the myocardium and the gastric mucosa. Tumor growth is linked with an enhanced prostanoid formation. Furthermore a rise of the PG content could be found in the liquor, aqueous humor and urine under diseases of the related organs. These results could be of some significance for diagnosis and therapy control.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aqueous Humor; Brain Diseases; Child; Gastric Mucosa; Gastritis; Guinea Pigs; Heart Diseases; Humans; Hypertension, Portal; In Vitro Techniques; Indomethacin; Kidney Transplantation; Myocardium; Skin Neoplasms; Thromboxane B2

Prostaglandins seem to play an important role in the protection of the gastric mucosa, but the effect of cytoprotective drugs such as sucralfate on prostaglandin synthesis and in the prevention of gastritis induced by gastric surgery has not been definitely established. The purpose of this study was to determine: (1) the prostanoid production and the histologic changes occurring after various surgical techniques in rat gastric mucosa; and (2) the influence of sucralfate treatment on prostanoid levels and gastric damage induced by gastric surgery. Animals included in the study had undergone one of three surgical procedures: Billroth I, Billroth II, or truncal vagotomy plus pyleroplasty. Animals that had no surgery and "sham-operated" animals were used as controls. One third of the animals in each group received sucralfate treatment (an average of 100 mg/kg per day). Samples of gastric mucosa were taken after one year, and prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, and thromboxane B2 synthesis were measured by radioimmunoassay. The sucralfate-treated group consistently showed higher PGE2 and 6-keto-PGF1 alpha values and a higher 6-keto-PGF1 alpha:thromboxane B2 ratio, as well as lower thromboxane B2 levels than untreated animals, although the differences were statistically significant only in the 6-keto-PGF1 alpha:thromboxane B2 ratio. Similarly, gastritis was more frequent and more severe in the untreated animals. In conclusion, sucralfate seems to provide protection against gastritis induced by gastric surgery and increases the 6-keto-PGF1 alpha:thromboxane B2 ratio.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprostone; Female; Gastrectomy; Gastric Mucosa; Gastritis; Prostaglandins; Rats; Rats, Inbred Strains; Sucralfate; Thromboxane B2; Vagotomy, Truncal

Because endogenous prostaglandins may protect the gastric mucosa a study was conducted to determine factors influencing the synthesis of immunoreactive prostaglandin (iPG) E2 and thromboxane (iTx) B2 as measured by radioimmunoassay and prostaglandin catabolism measured radiometrically, in human gastric mucosa. Gastric mucosa was obtained at endoscopy. Synthesis of iPE2 and iTxB2 was inhibited in vitro by indomethacin; iTxB2 synthesis was also selectively inhibited by the thromboxane synthesis inhibitor dazmegrel. Prostaglandin catabolism was inhibited by carbenoxolone. Multivariate analysis showed that synthesis of iPGE2 from endogenous precursor during homogenisation was decreased in patients on non-steroidal anti-inflammatory drugs. Mucosal inflammation was associated with significantly increased synthesis of iPGE2 and decreased prostaglandin catabolism. There were no differences between the mucosa of patients with or without gastric ulcers, nor between the ulcer rim and mucosa 5 cm away. Age, sex, smoking history and ingestion of antisecretory drugs appeared to exert no influence. In this study gastritis was the major influence on prostaglandin synthesis. It seems unlikely that prostaglandin deficiency is a strong predisposing factor for gastric ulceration.

Topics: Dinoprostone; Female; Gastric Mucosa; Gastritis; Humans; Indomethacin; Male; Prostaglandin Antagonists; Prostaglandins; Prostaglandins E; Radioimmunoassay; Stomach Ulcer; Thromboxane B2