geranylgeranylacetone and Gastritis

Controversy remains regarding the treatment of choice for chronic gastritis patients with dyspeptic symptoms when Helicobacter pylori eradication is not indicated or fails for their gastric lesions. A multicenter, randomized, double-blind trial was performed to compare the effectiveness of geranylgeranylacetone (GGA), a mucoprotective drug, against cimetidine (CIT), an H(2)-receptor antagonist, on the treatment of erosions and petechial hemorrhage in H. pylori-infected patients with dyspeptic symptoms.. 128 H. pylori-positive gastritis patients with mucosal erosions and/or petechial hemorrhage were randomized to receive 150 mg GGA t.i.d. or 400 mg CIT b.i.d. for 2 weeks. Improvement and cure rates on endoscopic findings, symptom disappearance rates, and changes in mucosal neutrophil infiltration were compared.. Endoscopic improvement rates were significantly higher in the GGA group (n = 50) than in the CIT group (n = 54; 86.0 vs. 64.8%, p = 0.014). Endoscopic cure rates were also significantly higher for GGA than for CIT (80.0 vs. 55.6%, p = 0.012). Symptom disappearance rates were 52.0% for GGA and 42.6% for CIT, but the difference was not significant. There was also no significant difference in mucosal neutrophil infiltration between the groups.. GGA treatment appears to be more effective than CIT for chronic gastritis-associated erosion and petechial hemorrhage.

Topics: Anti-Ulcer Agents; Cimetidine; Diterpenes; Double-Blind Method; Dyspepsia; Female; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Male; Middle Aged; Statistics, Nonparametric; Treatment Outcome

Upper gastrointestinal bleeding is a lethal complication after open heart surgery. We designed a prospective randomized trial to test the efficacy of different antisecretory agents to prevent upper gastrointestinal disease after operation.. A total of 210 patients were divided into 3 groups: group I had 70 patients who had mucosal protection (teprenone 150 mg/day), group II had 70 patients who had histamine2-receptor antagonist (ranitidine 300 mg/day), and group III included 70 patients who had a proton pump inhibitor (rabeprazole 10 mg/day). Gastric fiberscopy was used in all patients postoperatively during days 5 to 7. We compared the 3 groups in terms of endoscopic findings. Four patients (5.7%) had gastric bleeding complications in each of groups I and II; 2 died of coagulopathy. In group III no patients had gastric bleeding. The incidence of hemorrhagic gastritis was significantly higher in groups I (22.9%) and II (15.7%) than in III (2.9%) (p=0.0003). The incidence of active ulcers was also significantly higher in groups I (28.6%) and II (21.4%) than in III (4.3%) (p=0.0001).. Early medication postoperative by a proton pump inhibitor was shown to be the most effective treatment and indeed might be described as mandatory to prevent upper gastrointestinal diseases after open heart surgery.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Cardiac Surgical Procedures; Diterpenes; Endoscopy, Gastrointestinal; Gastritis; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Incidence; Omeprazole; Postoperative Complications; Premedication; Proton-Translocating ATPases; Rabeprazole; Ranitidine; Ulcer; Upper Gastrointestinal Tract

The role of teprenone in Helicobacter pylori-associated gastritis has yet to be determined. To investigate the effect of teprenone on inflammatory cell infiltration, and on H. pylori colonization of the gastric mucosa in H. pylori-infected patients, we first compared the effect of teprenone with that of both histamine H2 receptor antagonists (H2-RA) and sucralfate on the histological scores of H. pylori gastritis. We then examined its in vitro effect on H. pylori-induced interleukin (IL)-8 production in MKN28 gastric epithelial cells.. A total of 68 patients were divided into three groups, each group undergoing a 3-month treatment with either teprenone (150 mg/day), H2-RA (nizatidine, 300 mg/day), or sucralfate (3 g/day). All subjects underwent endoscopic examination of the stomach before and after treatment. IL-8 production in MKN28 gastric epithelial cells was measured by enzyme-linked immunosorbent assay (ELISA).. Following treatment, the teprenone group showed a significant decrease in both neutrophil infiltration and H. pylori density of the corpus (before vs. after: 2.49 +/- 0.22 vs. 2.15 +/- 0.23, p =.009; 2.36 +/- 0.25 vs. 2.00 +/- 0.24, p =.035, respectively), with no significant differences seen in either the sucralfate or H2-RA groups. Teprenone inhibited H. pylori-enhanced IL-8 production in MKN28 gastric epithelial cells in vitro, in a dose-dependent manner.. Teprenone may modify corpus H. pylori-associated gastritis through its effect on neutrophil infiltration and H. pylori density, in part by its inhibition of IL-8 production in the gastric mucosa.

Topics: Anti-Ulcer Agents; Biopsy; Cell Line; Diterpenes; Epithelial Cells; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Interleukin-8; Male; Middle Aged; Neutrophil Infiltration; Nizatidine; Pepsinogen A; Pepsinogen C; Sucralfate; Urease

Teprenone (Selbex), a gastric mucosal protective drug for treatment of chronic gastritis and gastric ulcer, has recently been used in the People's Republic of China. Teprenone in the treatment of chronic superficial gastritis (CSG): a surveillance study was recently conducted in 4 major hospitals in Beijing. The study included 98 patients (teprenone group 53 patients, Merzulene-S group 45 patients) with endoscopically proven gastritis. The study showed that teprenone may relieve symptoms of CSG in 8 weeks. The effectiveness rate for flatulence was 90.9% and for epigastralgia 87.2%. The improvement rate for the chronic inflammation in histopathology was 39.6% and disappearance rate for the activity of inflammation was 13.9%. It raised significantly the aminohexose level in gastric mucosa (P < 0.05) and increased gastric mucosal blood flow in gastric antrum (P < 0.05). These data suggest that teprenone is a safe and effective gastric mucosal protective drug.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; China; Diterpenes; Female; Gastric Mucosa; Gastritis; Humans; Male; Middle Aged

To establish a rat ethanol gastritis model, we evaluated the effects of ethanol on gastric mucosa and studied the preventive effects of geranylgeranylacetone on ethanol-induced chronic gastritis.. One hundred male Sprague-Dawley rats were randomly divided into 4 equal groups: normal control group, undergoing gastric perfusion of normal saline (NS) by gastrogavage; model control group and 2 model therapy groups that underwent gastric perfusion with ethanol (distillate spirits with 56% ethanol content) by gastrogavage for 4 wk. Low or high doses of geranylgeranylacetone were added 1 h before ethanol perfusion in the 2 model therapy groups, while the same amount of NS, instead of geranylgeranylacetone was used in that model control group. The rats were then sacrificed and stomachs were removed. The injury level of the gastric mucosa was observed by light and electron microscopy, and the levels of prostaglandin 2 (PGE₂), endothelin-1 (ET-1) and nitric oxide (NO) were measured by radioimmunoassay and the Griess method.. The gastric mucosal epidermal damage score (EDS; 4.5) and ulcer index (UI; 12.0) of the model control group were significantly higher than that of the normal control group (0 and 0 respectively, all P = 0.000). The gastric mucosal EDS and UI of the 2 model therapy groups (EDS: 2.5 and 2.0; UI: 3.5 and 3.0) were significantly lower than that of the model control group (all P < 0.01). There was no statistically significant difference between the low-dose and high-dose model therapy groups. The expression value of plasma ET-1 of the model control group was higher than that of the normal control group (P < 0.01) and the 2 model therapy groups (all P < 0.01). The expression values of gastric mucosal PGE₂ and serum NO of the model control group were lower than those of the normal control group (all P < 0.05) and the 2 model therapy groups (all P < 0.05). The thickness of the gastric mucous layerand the hexosamine content in the model control group were significantly lower than that in the normal control group (all P < 0.01) and the 2 model therapy groups (all P < 0.05). Scanning and transmission electron microscopy observation showed that in the model control group, the epithelial junctions were vague, the intercellular joints disappeared and damage of the intracellular organelles were significantly worse than those in the normal control group. However, in the 2 model therapy groups, damage to the intercellular joints and organelles was ameliorate relative to the model control group.. Administration of geranylgeranylacetone was correlated with a more favorable pattern of gastric mucosa damage after ethanol perfusion. The mechanism could be related to regulation of ET-1, NO and PGE₂.

Topics: Animals; Anti-Ulcer Agents; Cytoprotection; Dinoprostone; Disease Models, Animal; Diterpenes; Endothelin-1; Ethanol; Gastric Mucosa; Gastritis; Male; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Nitric Oxide; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Stomach Ulcer

The effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, CAS 11911-87-6) in preventing acute gastritis was examined in rats by stomach perfusion. Teprenone (CAS 6809-52-5), cimetidine (CAS 51481-61-9) and omeprazole (CAS 73590-58-6) were used as control drugs. Severe gastric hemorrhage was observed in conscious restrained rats, 1 h after treatment with indometacin (20 mg/kg i.p.). Pretreatment with rebamipide (3, 10 or 30 mg/kg s.c.) suppressed the hemorrhage induced by indometacin plus restraint stress, being more effective than teprenone or cimetidine. Pretreatment with omeprazole (30 mg/kg s.c.) did not suppress the gastric hemorrhage. Superoxide dismutase (30,000 U/kg s.c.) significantly decreased the hemorrhage. Anti-rat PMN (polymorphonuclear leukocytes), 1 ml/kg i.v., which caused depletion of circulating neutrophils, also suppressed the hemorrhage induced by indometacin plus restraint stress. Thus reactive oxygen species derived from neutrophils may play a role in the occurrence of the hemorrhage during acute gastritis induced by indometacin with restraint stress.

Topics: Acute Disease; Alanine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Catalase; Cimetidine; Diterpenes; Gastritis; Gastrointestinal Hemorrhage; Indomethacin; Leukocyte Count; Male; Neutrophils; Omeprazole; Perfusion; Quinolones; Rats; Rats, Wistar; Restraint, Physical; Stress, Psychological; Superoxide Dismutase

To evaluate the effects of teprenone on acute gastritis, its inhibitory effects on gastric mucosal damage were compared to that of gefarnate in taurocholate/hydrochloric acid-induced acute gastric mucosal lesions in rats. After oral administration of 160 mM taurocholic acid and 250 mM hydrochloric acid, hemorrhage and erosion were macroscopically observed in the gastric mucosal surface layer. Edema in the submucosal tissue and decreased PAS staining in the mucosa were histomorphologically observed. Concerning macroscopic findings, pretreatment with teprenone at a dose of 50 mg/kg or more significantly reduced pathological changes in the mucosa of the fundic glandular area. However, gefarnate slightly inhibited these changes in at a dose of 50 mg/kg and significantly inhibited them at a dose of 200 mg/kg. With regards to histomorphological findings in the fundic glandular area, teprenone slightly inhibited erosion at a dose of 50 mg/kg, and it significantly and slightly inhibited the decrease in PAS staining in this area at doses of 50 and 200 mg/kg, respectively. Gefarnate at doses of 50 and 200 mg/kg showed significant inhibition of decreased PAS staining in the fundic glandular area. In the pyloric mucosa, decreased PAS staining was slightly inhibited by teprenone at both doses but not by gefarnate at either dose. The differences between teprenone and gefarnate observed in this model appear to be due to their differences in mucus production ability. These results suggest that teprenone was more effective than gefarnate for the treatment of gastritis.

Topics: Acute Disease; Animals; Anti-Ulcer Agents; Disease Models, Animal; Diterpenes; Dose-Response Relationship, Drug; Gastric Mucosa; Gastritis; Gefarnate; Hydrochloric Acid; Male; Mucus; Rats; Rats, Wistar; Taurocholic Acid