leukotriene-b4 and Gastritis

Chronic non-specific pulmonary diseases are frequently followed by the development of inflammatory-degenerative and erosive-ulcerative processes in the mucous membrane of the stomach and duodenum. The literature date are presented on the frequency of combination of these conditions, the attempt is made to assess their link from the viewpoint of pathogenesis. Disturbances of respiratory lung function and hypoxia as well as non-respiratory metabolic functions of the pulmonary tissue are regarded as etiological factors of pathological processes in the gastro-duodenal area.

Topics: Adult; Angiotensins; Arachidonic Acid; Arachidonic Acids; Chronic Disease; Duodenal Diseases; Duodenitis; Female; Gastritis; Histamine; Humans; Hypoxia; Leukotriene B4; Lung; Lung Diseases; Male; Middle Aged; Peptic Ulcer; Prostaglandins; SRS-A; Stomach Diseases; Thromboxane A2

To investigate the effects of Clostridium butyricum (C. butyricum) on experimental gastric ulcers (GUs) induced by alcohol, restraint cold stress, or pyloric ligation in mice, respectively.. One hundred and twenty mice were randomly allocated into three types of gastric ulcer models (n = 40 each), induced by alcohol, restraint cold stress, or pyloric ligation. In each GU model, 40 mice were allocated into four groups (n = 10 each): the sham control group; model group (GU induction without pretreatment); C. butyricum group (GU induction with C. butyricum pretreatment); and Omeprazole group (GU induction with Omeprazole pretreatment). The effects of C. butyricum were evaluated by examining the histological changes in the gastric mucosal erosion area, the activities of superoxide dismutase (SOD) and catalase (CAT), the level of malondialdehyde (MDA), and the contents of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, leukotriene B4 (LTB4) and 6-keto-PGF-1α (degradation product of PGI2) in the gastric tissue.. Our data showed that C. butyricum significantly reduced the gastric mucosal injury area and ameliorated the pathological conditions of the gastric mucosa. C. butyricum not only minimized the decreases in activity of SOD and CAT, but also reduced the level of MDA in all three GU models used in this study. The accumulation of IL1-β, TNF-α and LBT4 decreased, while 6-keto-PGF-1α increased with pretreatment by C. butyricum in all three GU models.. Our data demonstrated the protective effects of pretreatment with C. butyricum on anti-oxidation and anti-inflammation in different types of GU models in mice. Further studies are needed to explore its potential clinical benefits.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Catalase; Clostridium butyricum; Cold Temperature; Disease Models, Animal; Ethanol; Gastric Mucosa; Gastritis; Inflammation Mediators; Interleukin-1beta; Leukotriene B4; Ligation; Male; Malondialdehyde; Mice, Inbred ICR; Omeprazole; Oxidative Stress; Probiotics; Proton Pump Inhibitors; Pylorus; Restraint, Physical; Stomach Ulcer; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Cyclooxygenases (COXs) play important roles in inflammation and carcinogenesis. The present study aimed to determine the effects of COX-1 and COX-2 gene disruption on Helicobacter pylori-induced gastric inflammation.. Wild-type (WT), COX-1 and COX-2 heterozygous (COX-1+/- and COX-2+/-), and homozygous COX-deficient (COX-1-/- and COX-2-/-) mice were inoculated with H. pylori strain TN2 and killed after 24 weeks of infection. Uninfected WT and COX-deficient mice were used as controls. Levels of gastric mucosal inflammation, epithelial cell proliferation and apoptosis, and cytokine expression were determined.. COX deficiency facilitated H. pylori-induced gastritis. In the presence of H. pylori infection, apoptosis was increased in both WT and COX-deficient mice, whereas cell proliferation was increased in WT and COX-1-deficient, but not in COX-2-deficient, mice. Tumor necrosis factor (TNF)-alpha and interleukin-10 mRNA expression was elevated in H. pylori-infected mice, but only TNF-alpha mRNA expression was further increased by COX deficiency. Prostaglandin E2 levels were increased in infected WT and COX-2-deficient mice but were at very low levels in infected COX-1-deficient mice. Leukotriene (LT) B4 and LTC4 levels were increased to a similar extent in infected WT and COX-deficient mice.. COX deficiency enhances H. pylori-induced gastritis, probably via TNF-alpha expression. COX-2, but not COX-1, deficiency suppresses H. pylori-induced cell proliferation.

Topics: Animals; Apoptosis; Cell Proliferation; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Gastric Mucosa; Gastritis; Gene Expression Regulation; Helicobacter Infections; Helicobacter pylori; Interleukin-10; Leukotriene B4; Leukotriene C4; Mice; Mice, Inbred C57BL; Mice, Knockout; RNA, Messenger; Tumor Necrosis Factor-alpha

CI-986 is a potent inhibitor of 5-lipoxygenase and cyclooxygenase pathway product biosynthesis from rat basophilic leukemia (RBL) cells. Because metabolites from these pathways have proinflammatory properties, CI-986 was evaluated in several acute and chronic models of inflammation and hyperalgesia. The compound inhibited swelling in the carrageenan footpad edema, Mycobacterium foot-pad edema and adjuvant arthritis models of inflammation with ID40 values of 1.0, 7.7., and 7.2 mg/kg, respectively. It was roughly equivalent in potency to the standard selective cyclooxygenase inhibitor, naproxen (ID40 = 0.7, 6.3, and 3.8 mg/kg, respectively). CI-986 was also evaluated in the acetic acid induced writhing hyperalgesia assay (ID50 = 0.23 mg/kg) and was approximately equipotent with indomethacin (ID50 = 0.87 mg/kg). Although the effects of CI-986 were similar to those of standard nonsteroidal antiinflammatory drugs (NSAIDs) in the inflammation models, its gastrointestinal profile was unique. CI-986 caused no gastrointestinal irritation at doses up to 200 mg/kg in acute and chronic studies. In contrast, standard NSAIDs caused ulcers at doses of 3.7-37 mg/kg after a single dose. Moreover, CI-986 inhibited the release of LTC4 and PGE2 by gastric mucosa and reduced mucosal and vascular damage induced by oral administration of absolute ethanol to rats. These results indicate that CI-986 is a potent nonulcerogenic antiinflammatory agent with novel pharmacologic properties.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Arthritis, Experimental; Cyclooxygenase Inhibitors; Dinoprost; Disease Models, Animal; Ethanol; Female; Gastritis; Inflammation; Leukotriene B4; Lipoxygenase Inhibitors; Male; Mice; Pain; Rats; Rats, Wistar; Thiadiazoles; Tumor Cells, Cultured

The effects of longstanding non-steroidal anti-inflammatory drug (NSAID) treatment on gastric mucosal synthesis of leukotriene B4 (LTB4), leukotriene C4 (LTC4), and prostaglandin E2 (PGE2) was studied. Gastric antral biopsies in 65 patients with arthritis taking NSAIDs and 23 control patients were taken and eicosanoid concentrations, stimulated by vortex mixing or calcium ionophore, were measured by radioimmunoassay. Median gastric mucosal synthesis of LTB4 was increased in patients taking NSAIDs compared with non-users: (0.9(0.2-2.5) pg/mg v 0 (0-0.6) pg/mg (p < 0.001)). These differences persisted when subgroups of patients were analysed according to Helicobacter pylori colonisation or degree of mucosal injury. Synthesis of LTB4 was strongly associated with the presence of type C (chemical) gastritis. Increased synthesis of LTC4 was associated with Helicobacter pylori colonisation but not NSAID use. Synthesis of PGE2 was decreased in patients taking NSAIDs compared with control patients (p < 0.001). Enhanced gastric mucosal synthesis of LTB4 in patients taking NSAIDs may represent a primary effect of these drugs and could be implicated in the pathogenesis of gastritis and ulceration associated with NSAIDs.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Dinoprostone; Female; Gastric Mucosa; Gastritis; Humans; Leukotriene B4; Male; Middle Aged; SRS-A; Stomach Ulcer

The effects and mechanism of action of PF-10040, a quinoline derivative, were examined in an experimental model of NSAID-gastritis. Oral pretreatment with PF-10040 dose-dependently reduced the severity of indomethacin-induced gastric damage, with a significant protective effect being observed with doses of 10 mg/kg or greater. The protective effects of this compound persisted for as long as 6 h after administration. PF-10040 also significantly reduced the severity of aspirin- or naproxen-induced gastric damage. At protective doses, PF-10040 did not significantly affect gastric LTB4 synthesis, LTB4-induced granulocyte recruitment to intradermal injection sites, or LTD4-induced changes in gastric blood flow. The free radical scavenging effects of PF-10040 were examined using an in vitro assay, in which it failed to exert significant effects at concentrations of up to 10 mM. PF-10040 had no significant effect on gastric acid secretion. In rat mesenteric venules, PF-10040 inhibited PAF-, but not LTB4-induced leukocyte adherence and emigration. These results suggest that the protective effects of PF-10040 are not attributable to scavenging of free radicals, inhibition of leukotriene synthesis, blockade of LTB4 or LTD4 receptors or inhibition of LTB4-mediated leukocyte endothelial cell adhesion.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Adhesion; Cell Movement; Disease Models, Animal; Free Radical Scavengers; Gastric Acid; Gastric Mucosa; Gastritis; Isoquinolines; Leukocytes; Leukotriene B4; Male; Platelet Activating Factor; Rats; Rats, Sprague-Dawley; Rats, Wistar; Stomach; Vasoconstriction

Forty patients suffering from peptic ulcer were examined for concentrations of leukotrienes B4 and C4 as compared to the activity of myeloperoxidase in the periulcerous zone of the gastric mucosa. 20 healthy persons made up the control. It is assumed that the rise of leukotrienes B4 and C4 concentrations as well as myeloperoxidase activation contribute to chronic inflammation in the periulcerous zone. Chronic inflammation of the gastric mucosa is regarded as an important pathogenetic factor of ulcerogenesis.

Topics: Adult; Arachidonic Acid; Arachidonic Acids; Female; Gastric Mucosa; Gastritis; Histamine H2 Antagonists; Humans; Leukotriene B4; Lipoxygenase; Male; Middle Aged; Peptic Ulcer; Peroxidase; SRS-A

This study was done to evaluate the role of leukotrienes (LTs) in gastritis associated with Campylobacter pylori. Biopsy specimens of gastric mucosa were obtained endoscopically from 18 patients with nonulcer dyspepsia for bacteriological and histological examination and extraction of LTs. There was correlation between the LTB4 level in the mucosa and the degree of gastritis evaluated histologically. The level was higher when infiltration of neutrophils in the gastric mucosa was more extensive. The LTB4 level in mucosa infected with C. pylori was higher than that in noninfected mucosa. These findings suggest that endogenous LTs may be related to the pathogenesis of gastritis associated with C. pylori.

Topics: Adult; Dyspepsia; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Leukotriene B4; Male; Middle Aged

Topics: Campylobacter Infections; Chronic Disease; Gastric Mucosa; Gastritis; Humans; Leukotriene B4