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Trametenolic acid B (TAB), the bioactive component in the Trametes lactinea (Berk.) Pat, was reported to possess cytotoxic activities and thrombin inhibiting effects. This study was performed to investigate the effects of TAB on H(+)/K(+)-ATPase and gastric cancer. The H(+)/K(+)-ATPase inhibitory activity was determined by gastric parietal cells. Compared to the normal control group, TAB (10, 20, 40 and 80 μg/mL) inhibited the H(+)/K(+)-ATPase activity by 15.97, 16.96, 24.86 and 16.25%, respectively. In the study, 36 Kunming mice were randomly divided into six groups: control, model, TAB-L (TAB, 5 mg/kg/day, i.g.), TAB-M (TAB, 20 mg/kg/day, i.g.), TAB-H (TAB, 40 mg/kg/day, i.g.) and omeprazole (OL, 10 mg/kg/day, i.g.). All mice except the control group were administrated with anhydrous alcohol (5.0 mL/kg, i.g.) for induced gastric-ulcer 1h after the 5th day. At the same time, the control mice were given the same volume of physiological saline. After 4h, TAB was evaluated for H(+)/K(+)-ATPase inhibitory activities of ulcerative gaster, gastric ulcer index and ulcer inhibition. In vitro, the anti-proliferation effect of TAB to gastric cancer cell (HGC-27) in acid environment was detected by MTT, and the apoptosis morphological changes were also observed by Hoechst 33258 dye assay. The results indicated that TAB inhibited moderately H(+)/K(+)-ATPase activity in vitro. Compared to the model group, TAB showed anti-ulcer effects in gastric tissue with the dosages of 20 and 5 mg/kg in vivo. Apart from that, TAB could selectively inhibit gastric cancer cell viability and reduce cell apoptosis against HGC-27 cells at low doses in acid environment., (Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

Gastric ulcer is a multifaceted process that involves reactive oxygen species (ROS) generation, extracellular matrix degradation and mitochondrial damage. Mitochondria play a crucial role for homeostasis of ROS and cell survival. In our study, we investigated the efficacy and mechanism of polymeric nanocapsuled quercetin (NQC) over the free quercetin (QC) molecule in prevention of ethanol-induced gastric ulcer in rat. NQC possessed significantly higher efficacy (~20 fold) than free QC while preventing gastric ulcers. Our data show that prior administration of NQC and/or QC significantly blocked synthesis and secretion of matrix metalloproteinase (MMP)-9 as well as infiltration of inflammatory cells and oxidative damage in rat gastric tissues. As compared to free QC, NQC protected much better the mitochondrial integrity and size along with mitochondrial functions by controlling succinate dehydrogenase and NADH oxidase in rat gastric tissues. In addition, both free QC and NQC down regulated PARP-1 as well as apoptosis during protection against ethanol-induced gastric ulcer. Herein, the effect of NQC was greater than QC on expression of enzymes like cyclooxygenase and nitric oxidase synthase (NOS)-2. We conclude that NQC with greater bioavailability offers significantly higher potency in downregulating MMP-9 and NOS-2 as well as oxidative stress in blocking ethanol-induced gastric ulcer., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To characterize the expression of the cyclooxygenase (COX)-1 and COX-2 isoforms in naturally occurring ulcers of the nonglandular portion of the stomach in horses. SPECIMEN POPULATION: 38 specimens from ulcerated stomachs and 10 specimens from healthy stomachs., Procedures: Specimens were collected at an abbatoir; for each specimen of squamous gastric mucosa, 1 portion was fixed in neutral-buffered 10% formalin for immunohistochemical analysis and another was frozen at -70 degrees C for immunoblotting analysis. Immunoreactivity to 2 antibodies, MF241 (selective for COX-1) and MF243 (selective for COX-2), was evaluated by a veterinary pathologist using a scoring system. Expression of COX-1 and COX-2 was confirmed by use of immunoblotting analyses., Results: All specimens from healthy stomachs strongly expressed COX-1, whereas only 2 of 10 expressed COX-2. The expression of both isoforms varied greatly in the ulcerated mucosal specimens. Expression of COX-1 was significantly lower and expression of COX-2 was significantly higher in ulcerated versus healthy specimens., Conclusions and Clinical Relevance: Increased expression of COX-2 in gastric ulcers of the squamous portion of the stomach in horses suggested a role for this enzyme in gastric ulcer healing.

This study investigated the effects of Onosma armeniacum K. (Boraginaceae) root extract (AR-1) on ethanol-induced stomach ulcers, and on some oxidant and antioxidant parameters, in stomach tissue in rats. The results obtained showed that AR-1 significantly inhibited ethanol-induced ulcers at 25, 50, 100 and 200 mg/kg doses. We found that 50, 100 and 200 mg/kg doses of AR-1 inhibited ulcers more effectively than did ranitidine. AR-1 at doses of 25, 50, 100 and 200 mg/kg significantly prevented the decrease in total glutathione (tGSH) level which occurs in damaged stomach tissues of rats given ethanol (control group). Only a 100 mg/kg dose of AR-1 significantly increased the glutathione S-transferase (GST) level in stomach tissue compared to the control. All doses of AR-1 except the 25 mg/kg dose eliminated the decrease in the superoxide dismutase (SOD) level in the stomach tissue of rats given ethanol. While all doses of AR-1 decreased malondialdehyde (MDA) levels significantly; all doses AR-1 except 25 mg/kg decreased myeloperoxidase (MPO) levels significantly compared to the control. The effect of AR-1 on catalase (CAT) activity was insignificant at all doses. AR-1 significantly increased nitric oxide (NO) levels at 50, 100 and 200 mg/kg doses compared to the control. Our results indicate that the protection of some antioxidant mechanisms and the inhibition of some oxidant mechanisms have a role in AR-1's antiulcer effect mechanism.

Histamine is involved in the development of gastric lesions. To examine the contribution of the histamine-forming enzyme, histidine decarboxylase, to drug-induced gastric lesions, we compared the effects of aspirin, indomethacin and dexamethasone on histidine decarboxylase activity in mice. Administration of these drugs, orally or intraperitoneally, elevated histidine decarboxylase activity in the stomach but not in the liver, lung or spleen, dexamethasone being the most potent. In contrast, acetaminophen (a non-ulcerogenic drug) was inactive. These results and our previously reported findings (elevation of histidine decarboxylase activity by lipopolysaccharide, interleukin-1 and tumour necrosis factor, and by different types of stress) suggest that an elevation of histidine decarboxylase activity in the stomach may be a common feature of the responses to ulcerogenic stimuli. The possible participation of histidine decarboxylase in gastric lesions is discussed on the basis of the known actions of histamine, our findings and the effect of histamine H(2) receptor antagonists on histidine decarboxylase activity.

A modification of Berstad's spectrophotometric method was tested and proved capable of detecting pepsin concentrations in mucosal perendoscopic biopsy homogenates. The relationship between this parameter and pepsin in gastric juice and pepsinogen group I in serum and in biopsy homogenates was analyzed. From the biochemical point of view, the assay was found sufficiently accurate. Mucosal pepsinogen group I, but not mucosal pepsin, concentration was found higher in gastric and duodenal ulcer patients than in controls. Patients with corpus-fundic gastric ulcer showed significantly lower mucosal pepsin and mucosal pepsinogen group (PG) I. Aging and smoking did not influence either parameter but male duodenal ulcer subjects presented higher mucosal pepsinogen group I concentration. The lack of any relationship between serum and mucosal PG I and between pepsin in gastric juice and in mucosa raises a question, at least in methodological terms, about the validity of using serum pepsinogen group I and pepsin as indicators of peptic output.

About half of Chinese individuals lack mitochondrial aldehyde dehydrogenase-2 (ALDH2) activity, which is responsible for the oxidation of acetaldehyde produced during ethanol metabolism. The ALDH2 deficiency in Chinese has been implicated in alcohol flush reaction and reported to be a negative risk factor for development of alcohol dependence. To assess the effects of inactive ALDH2 subunits, encoded by the mutant ALDH2(2) allele, on the catalytic activity of tetrameric enzyme molecules, we have phenotyped ALDH2 from 30 gastroendoscopic biopsies by using agarose isoelectric focusing and determined the genotypes from leukocytes of the same individuals by using polymerase-chain-reaction amplification and hybridization with allele-specific oligonucleotide probes. Sixteen subjects were homozygous for the ALDH2(1) allele, one was homozygous for ALDH2(2), and thirteen were the heterozygous genotype. None of the subjects with the mutant homozygotic and the heterozygotic genotypes exhibited the ALDH2 activity band or intermediate bands between ALDH2 and ALDH1 on isoelectric focusing gels. Our results support the notion that the mutant allele is dominant and that the heterotetrameric ALDH2 molecules containing the mutant subunits are enzymatically inactive or far less active.

Tryptase, a serine endoprotease, was determined in mucosal biopsies from fundus, corpus, antrum and corpus-fundus of the stomach and from the duodenum in 15 controls, 66 patients with duodenal ulcer, 22 with gastric ulcer and 9 with duodenitis. Intra- and inter-assay coefficients of variation ranged from 3.3% to 8.0% and from 3.5% to 8.6%, respectively. In controls, the highest values for tryptase were found in the fundus and progressively decreased in the corpus, antrum and duodenum. Analysis of variance of data from repeated measurements, performed in six subjects having multiple determinations, achieved statistical significance (F = 16.85, P less than 0.001). Data from the corpus-fundus area documented a significant difference among patient groups (F = 2.70, P less than 0.05). Patients with an active gastric ulcer had higher mean values when compared to controls and to patients with healed gastric ulcer. A similar trend was found in patients with active duodenal ulcer. Furthermore, corpus-fundus tryptase evaluated longitudinally in three patients with an active ulcer (point A) and after healing (point B), showed significant decrease from point A to point B. By contrast it remained elevated or showed only minor decrease in two patients with a persistent active ulcer.

In the experiments on Wistar rats we showed that administration of ulcerogenic drugs (cinchophen, acetylsalicylic acid, butadione, indomethacin etc.) produced the alterations of free activity of lysosomal enzymes in the homogenates of ulcerated stomachs, presumably the significant elevation of the activity of cathepsins (more often cathepsin with optimum of activity at pH 5.5) and the significant reduction of free activity of acid nucleases (more often of DNA-ase). The alterations of free activity of lysosomal enzymes were as in cases with gastric ulcerations as in cases with unaffected stomachs.

A technique for determining pepsinogen group I (PGI) concentrations in endoscopic gastroduodenal biopsies is described and validated. This method has a good precision (intra-assay CVs 4.1% to 8.4%; between-assay CVs 4.6% to 9.3%), and analytical recovery is satisfactory (94% to 102%). Results were uninfluenced by the storage interval of the samples. At PGI-producing sites (i.e., fundus, corpus) peptic activity was greater than in the antrum and duodenum. PGI concentrations in serum and in gastroduodenal biopsies were not correlated. This simple, reliable method can quantify better than other assays peptic activity in humans, without being influenced by gastric secretory volumes. It will also facilitate prospective studies on the effect of various secretagogues in vivo and evaluations of the influence of anti-ulcer drugs on peptic secretion.

A metalloproteinase was extracted from a medium of cultured gastric tissues following acetic acid-induced ulcer or taurocholic acid-induced gastritis, and the enzyme was partially purified by Sephadex G-200 column chromatography. This proteinase was released in active and latent forms with apparent molecular weights of 170,000 and 210,000, respectively. Its activity was abolished by treatment with ethylenediaminetetraacetic acid or 1,10-phenanthroline, but not with phenylmethylsulfonyl fluoride or soybean trypsin inhibitor. This enzyme degraded type I gelatin and type IV collagen but did not attack type I collagen. In contrast, very little of this enzyme was released from gastric tissue following erosion caused by water-immersion stress or from normal gastric tissue. These results suggest that this metalloproteinase plays an important role in gastric lesions by breaking down the basement membrane.

Gastric acidity was evaluated, using the histamine test (Key's test), measurement of nocturnal gastric secretion and gastric pH-metry, in 174 patients with gastric ulcers. Acidity proved to be lowered in 25% of gastric ulcers patients, normal in 30% and increased in nearly half of the patients. Intragastric proteolysis was studied in 48 individuals, including 27 patients with peptic ulcers and 21 normal controls. It was found to be normal in the overwhelming majority of peptic ulcer patients (74%). It is concluded that intragastric proteolysis can only be regarded as an aggressive factor, resulting in the formation of a gastric ulcer, when it is combined with high acidity.

New data have been made available which confirm the existence of differing quateron sensitivity of tissular monaminoxidases possessing dissimilar substrate specificity. An experimental neurogenic dystrophy of the stomach is attended on the whole by an activated deamidization of monamines, but there could be seen marked differences in the ability to intensify oxidation depending upon the localization of the mitochondrial monaminoxidases in various parts of the stomach. When introduced to intact animals in a dose of 5 mg/kg quateron tends to lower the activity of mitochondrial monaminoxidases in individual receptor areas of the stomach with respect to norepinephrine and, especially, serotonin. In such instances preliminary introduction of quateron prevents an activated oxidation of norepinephrine and serotonin, observed 24 hours after inflicting an injury. In the mechanisms governing deposition of catecholamines and serotonin in the gastric wall occurring under the effect of quateron a definite role plays also the inhibition of the mitochondrial monaminoxidases.

To clarify the destruction of connective tissue in ulcerated regions, collagenase and gelatinolytic activities in homogenates of rat acetic acid-induced ulcers were examined. Gelatinolytic activity in the ulcerated regions was significantly higher than that in normal tissues. Collagenase, however, was not detectable. Gelatin-gel-electrophoresis showed that the gelatinolytic activity was due to several species, some of which crossreacted with a sheep anti-(rabbit prostromelysin) antibody. The H2-blocker, famotidine, significantly depressed the gelatinolytic activity in the ulcerated regions. Thus, both stromelysin and gelatinolytic enzymes may play important roles in the degradation of the basement membrane, especially type IV collagen.