Amelioration of alcohol­induced gastric mucosa damage by oral administration of food­polydeoxyribonucleotides.

Gastritis refers to inflammation caused by injury to the gastric epithelium, which is usually due to excessive alcohol consumption and prolonged use of nonsteroidal anti­inflammatory drugs. Millions of individuals worldwide suffer from this disease. However, the lack of safe and promising treatments makes it urgent to explore and develop leads from natural resources. Therefore, food as medicine may be the best approach for the treatment of these disorders. The present study described the protective effects of food­polydeoxyribonucleotides (f­PDRNs) in a rat model of gastric mucosal injury induced by HCl­EtOH. Administration of f­PDRN was performed with low­PRF002 (26 mg/kg/day), medium­PRF002 (52 mg/kg/day) and high­PRF002 (78 mg/kg/day) on the day of autopsy. The site of damage to the mucous membrane was also analysed. In addition, an increase in gastric juice pH, total acidity of gastric juice and decrease in gastric juice secretion were confirmed, and gastric juice secretion­related factors corresponding to the administration of f­PDRN were analysed. Administration of f­PDRN reduced the mRNA expression of histamine H2 receptor, muscarinic acetylcholine receptor M3, cholecystokinin 2 receptor and H+/K+ ATPase related to gastric acid secretion and downregulation of histamine, myeloperoxidase and cyclic adenosine monophosphate. In addition, it was histologically confirmed that the loss of epithelial cells and the distortion of the mucosa were recovered in the group in which f­PDRN was administered compared to the model group with gastric mucosa damage. In summary, the present study suggested that f­PDRN has therapeutic potential and may have beneficial effects if taken regularly as a food supplement.

Is gastrointestinal motility related to alkaloids of Charred Semen Arecae?

ETHNOPHARMACOLOGICAL RELEVANCE: Semen Arecae (SA) is one of the most commonly used Traditional Chinese Medicine. Charred Semen Arecae (CSA) is the processed product of SA. Alkaloids are considered as pharmacological mechanisms of SA and CSA on gastrointestinal motility. Recent studies have shown alkaloids decreased quickly after procession. However, the promoting on gastrointestinal motility were not decreased. Is gastrointestinal motility related to alkaloids of CSA? This study explored the effects of SA, CSA, Semen Arecae-Removal (SA-R), and Charred Semen Arecae-Removal (CSA-R) on gastrointestinal motility, Gastric Inhibitory Polypeptide (GIP), Glucagon Like Peptide-1 (GLP-1), gastric juice and bile in rats. MATERIAL AND METHODS: Rats were randomly divided into six groups, including the Control group, SA group, CSA group, SA-R group, CSA-R group, and Positive drug group (Mosapride). Alkaloids of samples were knocked out by using the "target constituent removal" strategy. Gastric residue and intestinal propulsion rate were evaluated in rats. Serum levels of GIP and GLP-1 were measured by Enzyme-Linked Immunosorbent Assay (ELISA). Gastric juice and bile were examined, respectively. RESULTS: CSA-R and SA-R have been investigated by the Preparative Thin-layer Chromatography (PTLC) method. Intestinal propulsion and gastric residue assessments confirmed the effectiveness of CSA and CSA-R. CSA-R was higher than SA-R in the GLP-1, pepsin activity, the secretion of bile, Bilirubin (BIL), and Cholesterol (CHO). The statistical comparison demonstrated that there is no difference between the CSA group and CSA-R group. CONCLUSIONS: After processing, the promoting gastrointestinal motility might be not related to alkaloids. Maillard reaction could be produced to promote the secretion of GLP-1, bile, and CHO for gastrointestinal motility. Our findings provide a pharmacological reference for the clinical application of SA and CSA in the treatment of digestive diseases.

Pretreatment with Lactobacillus fermentum XY18 Relieves Gastric Injury Induced by HCl/Ethanol in Mice via Antioxidant and Anti-Inflammatory Mechanisms.

AIM: Lactobacillus fermentum XY18 (LF-XY18) is a bacterial strain with satisfactory antioxidant properties in vitro that we previously isolated from Xinjiang yogurt. This article will explore the preventive effect of LF-XY18 on acute gastric injury and provide the basis for the innovative development and application of lactic acid bacteria (LAB). METHODS: Kunming mice underwent gastric injury induced by hydrochloric acid and ethanol. LF-XY18 isolated from yogurt in Xinyuan County in the Yili region of Xinjiang was subsequently administered intragastrically to mice for 2 weeks to explore the mechanism of LF-XY18 in preventing gastric injury via its antioxidant effects. RESULTS: There was decreased gastric juice volume, gastric injury area, and formation of gastric mucosal lesions in the LF-XY18 mice as compared to those in the control mice, while LF-XY18 prevented the decrease in the gastric juice pH value in mice. Compared with the gastric injury model group mice, LF-XY18 reduced the serum levels of motilin, substance P, interleukin-6, interleukin-12, tumor necrosis factor-α, and interferon-γ but increased the serum levels of somatostatin and vasoactive intestinal peptide. The activities of superoxide dismutase, glutathione peroxidase, glutathione, and nitric oxide were increased in the gastric tissue of the LF-XY18 mice compared with the control mice, but malondialdehyde activity was decreased in the LF-XY18 mice. Quantitative polymerase chain reaction analysis illustrated that in the gastric tissue of LF-XY18 mice, the messenger RNA (mRNA) expression of occludin, epidermal growth factor (EGF), EGF receptor, vascular EGF, inhibitor kappa-B-α, neuronal nitric oxide synthase, endothelial nitric oxide synthase, cuprozinc superoxide dismutase, manganese superoxide dismutase, and catalase was stronger than that in the control mice, but the mRNA expression of activated B cells (NF-κB), inducible nitric oxide synthase, and cyclooxygenase-2 was weaker than in the control mice. CONCLUSION: These results indicate that LF-XY18 has a potential role in the prevention of gastric injury through antioxidant effects, and a high concentration (1.0 × 109 CFU/kg b.w.) of LF-XY18 has a stronger anti-gastric injury effect than a low concentration (1.0 × 108 CFU/kg b.w.).

Gastroprotective effect of araloside A on ethanol- and aspirin-induced gastric ulcer in mice: involvement of H+/K+-ATPase and mitochondrial-mediated signaling pathway.

The aim of this study was to elucidate the gastroprotective activity and possible mechanism of involvement of araloside A (ARA) against ethanol- and aspirin-induced gastric ulcer in mice. The experimental mice were randomly divided into control, model, omeprazole (20 mg/kg, orally) and ARA (10, 20 and 40 mg/kg, orally). Gastric ulcer in mice was induced by intragastric administration of 80% ethanol (10 mL/kg) containing 15 mg/mL aspirin 4 h after drug administration on day 7. The results indicated that ARA could significantly raise gastric juice volume and acidity; ameliorate gastric mucosal blood flow, gastric binding mucus volume, ulcer index and ulcer inhibition rate; suppress H+/K+-ATPase activity, which was confirmed by computer-aided docking simulations; inhibit the release of mitochondrial cytochrome c into the cytoplasm; inhibit caspase-9 and caspase-3 activities and down-regulate mRNA expression levels; down-regulate the mRNA and protein expressions of apoptosis protease-activating factor-1 and protein expression of cleaved poly(ADP ribose) polymerase-1; and up-regulate Bcl-2 mRNA and protein expressions and down-regulate Bax mRNA and protein expressions, thus elevating the Bcl-2/Bax ratio in a dose-dependent manner. Histopathological observations further provided supportive evidence for the aforementioned results. The results demonstrated that ARA exerted beneficial gastroprotective effects on alcohol- and aspirin-induced gastric ulcer in mice, which was related to suppressing H+/K+-ATPase activity as well as pro-apoptotic protein expression, and promoting anti-apoptotic protein expression, thus alleviating gastric mucosal injury and cell death.

Artesunate affords protection against aspirin-induced gastric injury by targeting oxidative stress and proinflammatory signaling.

BACKGROUND: Prolonged use of aspirin, a commonly prescribed non steroidal anti-inflammatory drug, is well known to produce gastrointestinal toxicity which could be minimized by various anti-secretory agents. The present study was carried out to evaluate the protective effect of artesunate against aspirin induced gastric injury in rats. METHODS: Gastric injury was induced in fasted Wistar rats by oral administration of aspirin. The effect of 50 and 150mg/kg of artesunate was studied on macroscopic changes, gastric secretions, histology, oxidative stress and inflammatory markers in the stomach tissue after 5h of induction of gastric injury. Immunohistochemical analysis for the expression of IL-1ß, IL-6, NF-κB(p65) and COX-2 was also carried out. The effect of artesunate was compared with that of standard anti-ulcer drug famotidine (20mg/kg). RESULTS: Artesunate pretreatment produced a dose-dependent reduction in aspirin induced gastric injury and restored the gastric juice parameters. It normalized the tissue levels of oxidative stress markers (glutathione, malondialdehyde and superoxide dismutase activity) and mediators of inflammation (myeloperoxidase and TNF-α). The protection afforded by artesunate was evident from the histoarchitecture of stomach tissue and marked reduction in tissue expression of IL-1ß, IL-6, NF-κB(p65) and COX-2. The effect of artesunate was found to be comparable to that of standard drug famotidine. CONCLUSION: Artesunate markedly ameliorated aspirin induced gastric injury in rats by targeting oxidative stress and COX-2 dependent as well as COX-2 independent proinflammatory signaling pathways and could have a therapeutic potential in gastric ulcer disease.

Tegoprazan, a Novel Potassium-Competitive Acid Blocker to Control Gastric Acid Secretion and Motility.

Tegoprazan [(S)-4-((5,7-difluorochroman-4-yl)oxy)-N,N,2-trimethyl-1H-benzo[d]imidazole-6-carboxamide], a potassium-competitive acid blocker (P-CAB), is a novel potent and highly selective inhibitor of gastric H+/K+-ATPase. Tegoprazan inhibited porcine, canine, and human H+/K+-ATPases in vitro with IC50 values ranging from 0.29 to 0.52 µM, while that for canine kidney Na+/K+-ATPase was more than 100 µM. A kinetic analysis revealed that tegoprazan inhibited H+/K+-ATPase in a potassium-competitive manner and the binding was reversible. Oral single administrations of tegoprazan ranging from 0.3 to 30 mg/kg in dogs were well absorbed into the blood stream and distributed in gastric tissue/fluid higher than in plasma. Tegoprazan potently inhibited histamine-induced gastric acid secretion in dogs, and a complete inhibition was observed at 1.0 mg/kg starting from 1 hour after administration. Moreover, an oral administration of tegoprazan at 1 and 3 mg/kg reversed the pentagastrin-induced acidified gastric pH to the neutral range. Interestingly, 3 mg/kg tegoprazan immediately evoked a gastric phase III contraction of the migrating motor complex in pentagastrin-treated dogs and similar effects was observed with the other P-CAB, vonoprazan. Tegoprazan is the novel P-CAB that may provide a new option for the therapy of gastric acid-related and motility-impaired diseases.

Prophylactic effects of Clausena excavata Burum. f. leaf extract in ethanol-induced gastric ulcers.

Clausena excavata is a natural herb with both antioxidant and anti-inflammatory properties. It has been used for decades in folkloric practice for the amelioration of various ailments. In this study, the gastroprotective activity of methanolic extract of C. excavata leaves (MECE) was determined in the Sprague Dawley rat ethanol-induced gastric ulcer model. Rats were pretreated with a single dose of vehicle (5% Tween 20), 20 mg/mL omeprazole, 400 and 200 mg/mL of MECE dissolved in 5% Tween 20. Ulcer was induced with 5 mL/kg of ethanol and stomach tissue was obtained after 1 hour. Histological examination was done on hematoxylin and eosin, periodic acid-Schiff, and immunochemically stained gastric mucosal tissues. Prostaglandin E2, superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation levels of the gastric tissue homogenates were also determined. Significantly (P<0.05) smaller ulcer areas, less intense edema, and fewer leukocytes' infiltration were observed in MECE- and omeprazole-treated than in untreated gastric mucosa with ulcer. The gastric pH, mucus production, superoxide dismutase, catalase, and glutathione peroxidase contents increased, while the lipid peroxidation content decreased as a result of MECE treatment. Bcl-2-associated X protein was underexpressed, while heat shock protein 70 and transforming growth factor-beta protein were overexpressed in the ulcerated gastric mucosa tissues treated with omeprazole and MECE. Similarly, there was a reduction in the levels of tumor necrotic factor-alpha and interleukin-6, while the level of interleukin-10 was increased. This study showed that the gastroprotective effect of MECE is achieved through inhibition of gastric juice secretion and ulcer lesion development, stimulation of mucus secretion, elevation of gastric pH, reduction of reactive oxygen species production, inhibition of apoptosis in the gastric mucosa, and modulation of inflammatory cytokines.

Apocynin protects against ethanol-induced gastric ulcer in rats by attenuating the upregulation of NADPH oxidases 1 and 4.

Gastric ulcer is a common gastrointestinal disorder affecting many people all over the world. Absolute ethanol (5 ml/kg) was used to induce gastric ulceration in rats. Apocynin (50 mg/kg) was given orally one hour before the administration of absolute ethanol. Omeprazole (20 mg/kg) was used as a standard. Interestingly, apocynin pre-treatment provided 93.5% gastroprotection against ethanol-induced ulceration. Biochemically, gastric mucin content was significantly increased with apocynin pre-treatment. This finding was further supported by alcian blue staining of stomach sections obtained from the different treated groups. Also, gastric juice volume and acidity were significantly reduced. Apocynin significantly ameliorated ethanol-induced oxidative stress by replenishing reduced glutathione and superoxide dismutase levels as well as reducing elevated malondialdehyde levels in gastric tissues. Besides, ethanol-induced pro-inflammatory response was significantly decreased by apocynin pre-treatment via reducing elevated levels of pro-inflammatory markers; interleukin-1ß, tumor necrosis factor-α, cyclooxygenase-2 and inducible nitric oxide synthase. Additionally, caspase-3 tissue level was significantly reduced in apocynin pre-treated group. Interestingly, NADPH oxidase-1 (NOX-1) and NOX-4 up-regulation was shown to be partially involved in the pathogenesis of ethanol-induced gastric ulceration and was significantly reversed by apocynin pre-treatment. Gastroprotective properties of apocynin were confirmed by histopathological examination. It is worth mentioning that apocynin was superior in all aspects except gastric mucin content parameter where it was significantly increased by 13.5 folds in the omeprazole pre-treated group. This study was the first to show that apocynin is a promising gastroprotective agent against ethanol-induced gastric ulceration, partially via its anti-oxidant, anti-inflammatory, anti-apoptotic effects as well as down-regulating NOX-1 and NOX-4 expression.

Antisecretory, gastroprotective, antioxidant and anti-Helicobcter pylori activity of zerumbone from Zingiber zerumbet (L.) Smith.

BACKGROUND: Zingiber zerumbet Smith is a perennial herb, broadly distributed in many tropical areas. In Malaysia, it's locally known among the Malay people as "lempoyang" and its rhizomes, particularly, is widely used in traditional medicine for the treatment of peptic ulcer disease beyond other gastric disorders. AIM OF THE STUDY: The aim of the current study is to evaluate the gastroprotective effect of zerumbone, the main bioactive compound of Zingiber zerumbet rhizome, against ethanol-induced gastric ulcer model in rats. MATERIALS AND METHODS: Rats were pre-treated with zerumbone and subsequently exposed to acute gastric ulcer induced by absolute ethanol administration. Following treatment, gastric juice acidity, ulcer index, mucus content, histological analysis (HE and PAS), immunohistochemical localization for HSP-70, prostaglandin E2 synthesis (PGE2), non-protein sulfhydryl gastric content (NP-SH), reduced glutathione level (GSH), and malondialdehyde level (MDA) were evaluated in ethanol-induced ulcer in vivo. Ferric reducing antioxidant power assay (FRAP) and anti-H. pylori activity were investigated in vitro. RESULTS: The results showed that the intragastric administration of zerumbone protected the gastric mucosa from the aggressive effect of ethanol-induced gastric ulcer, coincided with reduced submucosal edema and leukocyte infiltration. This observed gastroprotective effect of zerumbone was accompanied with a significant (p <0.05) effect of the compound to restore the lowered NP-SH and GSH levels, and to reduce the elevated MDA level into the gastric homogenate. Moreover, the compound induced HSP-70 up-regulation into the gastric tissue. Furthermore, zerumbone significantly (p <0.05) enhanced mucus production, showed intense PAS stain and maintained PG content near to the normal level. The compound exhibited antisecretory activity and an interesting minimum inhibitory concentration (MIC) against H. pylori strain. CONCLUSION: The results of the present study revealed that zerumbone promotes ulcer protection, which might be attributed to the maintenance of mucus integrity, antioxidant activity, and HSP-70 induction. Zerumbone also exhibited antibacterial action against H. pylori.

Curcumin-induced histone acetylation inhibition improves stress-induced gastric ulcer disease in rats.

Curcumin is known to possess anti­inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+­ATPase activity, the mechanism underlying the curcumin­induced inhibition of the transcription of the H+, K+­ATPase α subunit in gastric mucosal parietal cells remains unclear. The present study investigated the possible mechanism by which curcumin inhibits stomach H+, K+­ATPase activity during the acute phase of gastric ulcer disease. A rat model of stress­induced gastric ulcers was produced, in which the anti­ulcer effects of curcumin were examined. Curcumin­induced inhibition of the H+, K+­ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress­induced gastric ulcer disease in rats, as demonstrated by increased pH values and reduced gastric mucosal hemorrhage and ulcer index. These effects were accompanied by a significant reduction in the level of histone H3 acetylation at the site of the H+, K+­ATPase promoter and in the expression of the gastric H+,K+­ATPase α subunit gene and protein. In conclusion, curcumin downregulated the acetylation of histone H3 at the site of the H+, K+­ATPase promoter gene, thereby inhibiting the transcription and expression of the H+, K+­ATPase gene. Curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease.

Accumulation of mercury and cadmium in rice from paddy soil near a mercury mine.

Paddy soil and rice (Oryza sativa L.) in the Wanshan mining area in Guizhou Province, China, have been contaminated by toxic trace metals such as cadmium (Cd) and mercury (Hg). The present study examined correlations between the types and physicochemical parameters of the soil and the contents of trace metals and the different forms of Hg in rice. The health risks of consuming contaminated rice from the Wanshan mining area were also assessed. Sequential extraction procedures were used to investigate the chemical behavior of Hg in the soil. The results showed that Hg and Cd were the most abundant trace metals in the Wanshan mining area. The toxic methylmercury (MeHg) content was substantial in brown rice, and the total amounts of total Hg (THg), diethylenetriaminepentaacetic acid-Hg, and water-soluble Hg varied in the rhizosphere and non-rhizosphere soils. An antagonistic interaction between Mn in brown rice, straw, and husk and MeHg in brown rice was also shown. An analysis of calculated dietary intake, target hazard quotients, and hazard indexes showed a potential risk of transferring Hg, MeHg, and Cd to humans when rice from the Wanshan mining area is consumed. Therefore, it must be concluded that consuming contaminated rice near the Wanshan mining area is a potential threat to human health.

Protective effect of chelerythrine against ethanol-induced gastric ulcer in mice.

The quaternary benzo[c]phenanthridine alkaloid, chelerythrine (CHE), is of great practical and research interest because of its pronounced, widespread physiological effects, primarily antimicrobial and anti-inflammatory, arising from its ability to interact with proteins and DNA. Although CHE was originally shown to possess anti-inflammatory properties, its effects on acute gastric ulcer have not been previously explored. The aim of the present study is to evaluate the protective effect of CHE on ethanol induced gastric ulcer in mice. Administration of CHE at doses of 1, 5 and 10mg/kg bodyweight prior to ethanol ingestion dose-dependently inhibited gastric ulcer. The gastric mucosal lesion was assessed by ulcer area, gastric juice acidity, myeloperoxidase (MPO) activities, macroscopic and histopathological examinations. CHE significantly reduced the gastric ulcer index, myeloperoxidase activities, macroscopic and histological score in a dose-dependent manner. In addition, CHE also significantly inhibited nitric oxide (NO) concentration, pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) level in serum and gastric mucosal in the mice exposed to ethanol induced ulceration in a dose-dependent manner. In addition, immunohistochemical analysis revealed that CHE markedly attenuated the overexpression of nuclear factor-κB in gastric mucosa of mice. It was concluded that CHE represents a potential therapeutic option to reduce the risk of gastric ulceration. In addition, acute toxicity study revealed no abnormal sign to the mice treated with CHE (15mg/kg). These findings suggest that the gastroprotective activity of CHE might contribute in adjusting the inflammatory cytokine by regulating the NF-κB signalling pathway.

Efecto gastroprotector y antisecretor de un fitofármaco de hojas de matico (Piper aduncum) / Gastroprotective and antisecretory effect of a phytochemical made from matico leaves (Piper aduncum)

Objetivos. Determinar el efecto gastroprotector y antisecretor del extracto etanólico de las hojas de matico (Piper aduncum) en modelos animales. Materiales y métodos. Para la evaluación del efecto gastroprotector se utilizó 220 ratones de la cepa Balb C57, los cuales fueron aleatorizados en 22 grupos de diez animales, a los cuales se les indujo la formación de úlceras gástricas con indometacina, la gastroprotección se determinó a través de tres aspectos: inflamación, número de bandas hemorrágicas y número de úlceras. Para evaluar el efecto antisecretor se utilizó 64 ratas albinas machos Holtzman, los cuales fueron aleatorizados en ocho grupos de ocho animales, un control y siete grupos de tratamiento con un nivel de dosis de los extractos y dos niveles de dosis en los fitofármacos; la antisecreción se realizó con el ensayo de ligazón pilórica. Resultados. Para la gastroprotección, los extractos de diclorometano, cloroformo, hexano y metanol, lograron una disminución de la inflamación de más del 66% (p<0,05); el extracto etanólico presenta una actividad de 100% para disminuir el número de bandas hemorrágicas (p<0,05); el extracto clorofórmico presenta una actividad antiulcerosa de 75% (p<0,05). Respecto a la antisecreción, el fitofármaco en cápsulas conteniendo el extracto etanólico logró un 72% de reducción del volumen de la secreción gástrica (p<0,01) y un incremento del pH en 104,3% (p<0,01). Conclusiones. En condiciones experimentales los extractos etanólico, sus fracciones y su fitofármaco son gastroprotectores en ratones y antisecretores en ratas.

Objectives. To determine the gastroprotective and antisecretory effect of ethanol extract from matico leaves (Piper aduncum) in animal models. Materials and methods. To evaluate the gastroprotective effect, 220 mice of the Balb C57 strain were used. They were randomized in 22 groups of ten animals each, in which the formation of gastric ulcers was induced with indomethacin. Gastroprotection was determined by evaluating three aspects: inflammation, number of hemorrhagic shocks and number of ulcers. To evaluate the antisecretory effect, 64 white male Holtzman rats were used, which were randomized in eight groups of eight animals, one control and seven groups of treatment with one extract dose level and two phytochemical dose levels. Antisecretion was obtained through the pylorus ligation. Results. Regarding gastroprotection, dichloromethane, chloroform, hexane and methanol extracts decreased inflammation to over 66% (p<0,05). The ethanolic extract shows 100% activity in reducing the number of hemorrhagic bands (p<0,05). The chloroform extract shows antiulcer activity at 75% (p<0,05). In terms of antisecretion, the phytochemical in capsules containing the ethanolic extract achieved 72% reduction of the gastric secretion volume (p<0,01) and 104,3% (p<0,01) PH increase. Conclusions. In experimental conditions, ethanolic extracts, their fractions and phytochemicals have a gastroprotective effect in mice and antisecretory effect in rats.

[The influence of corvitin on secretory processes and blood flow in the rat gastric mucosa].

We studied parameters of gastric secretion in pylorus-ligated rat and blood flow in the rat gastric mucosa under the influence of drug corvitin used intragastrically in doses of 2.5 and 5 mg/kg. Biochemical analysis of gastric juice was based on the determination of pH, total hydrochloric acid production and total protein, hexosamine and cysteine concentration. Gastric juice analysis in control rats found the presence of hexosamines-- a gastric mucus indicators and cysteine--free amino acid whith properties of a strong antioxidant. Concentration of these compounds in the gastric juice increased as a consequence of corvitin action. However, corvitin did not affect at these parameters of gastric secretion as the volume of gastric juice, pH, hydrochloric acid output rate, protein concentration. Additionally it was shown that corvitin in dose-dependent manner increased blood flow in the gastric mucosa. This results give reason to believe that corvitin can be considered as a tool that amplifies gastric mucosal defense mechanisms without affecting the secretion of gastric hydrochloric acid and total protein.

Changes in gastric pH and in pharmacokinetics of ulipristal acetate - a drug-drug interaction study using the proton pump inhibitor esomeprazole.

OBJECTIVE: Ulipristal acetate is a novel selective progesterone receptor modulator for the treatment of benign gynecological conditions such as uterine myoma. As a Biopharmaceutical Classification System (BCS) II compound, it is highly soluble at low pH but has low solubility at neutral conditions. Esomeprazole, a proton pump inhibitor used widely for treatment of gastric and duodenal ulcers, efficiently increases gastric pH. Thus, the aim of this study was to determine the effects of esomeprazole on the pharmacokinetics of ulipristal acetate. MATERIALS AND METHODS: This was a nonrandomized, single sequence, 2 period, open, study in 18 healthy female subjects. Subjects received oral ulipristal acetate tablets (10 mg) once on Days 1 and 13 and daily esomeprazole administrations (20 mg) from Days 9 through 14. RESULTS: Co-administration of esomeprazole decreased geometric mean Cmax of ulipristal acetate by 65% (geometric mean ratio point estimate (90% CI): 0.35 (0.28 - 0.42)), and delayed median tmax from 0.75 to 1.00 h (Hodges-Lehmann estimate of difference (90% CI): tmax 0.63 (0.25 - 1.25)) but had minor effects on AUCs of +15% and +11% (geometric mean ratio point estimates (90% CI): AUC0-t 1.15 (1.02 - 1.31) and AUC0-∞ (1.11 (0.98 - 1.27)), respectively. A total of 6 adverse events were reported by 4 subjects, none of them being serious. CONCLUSIONS: Concomitant use of ulipristal acetate with esomeprazole at therapeutic concentrations led to a modified absorption rate while exposure in terms of AUC remained close to bioequivalence limits. In the context of chronic administration of ulipristal acetate, no clinically significant effects are expected from co-administration with drugs increasing gastric pH.

Drugs that inhibit gastric acid secretion may alter the course of inflammatory bowel disease.

BACKGROUND: Recent data suggest that acid suppressive medications may alter factors central to the pathophysiology of inflammatory bowel diseases (IBD), whether through shifts in the intestinal microbiome due to acid suppression or effects on immune function. AIM: To assess the relationship between the use of proton pump inhibitors (PPIs) or histamine2-receptor antagonists (H2Ra) and incidence of 'flares' (hospitalisation/surgery and change in medication). METHODS: We conducted a new user cohort study including individuals diagnosed with IBD in British Columbia using linked healthcare utilisation databases (available from July 1996 through April 2006). Propensity-score matched incidence rates during a 6-month follow-up period and rate ratios (RR) and 95% CI were calculated. RESULTS: Among 16 151 IBD patients, 1307 Crohn's disease (CD) and 996 ulcerative colitis (UC) patients experienced a new use of PPIs, whereas 741 CD and 738 UC used H2Ra. All IBD subgroups were matched separately to an equal number of unexposed IBD patients. H2Ra use in CD doubled the risk of hospitalisation/surgery (RR = 1.94; 95%CI 1.24-3.10) and numerically less so in UC patients (RR = 1.11) with widely overlapping CIs (0.61-2.03). Proton pump inhibitors use was associated with medication change in UC (RR = 1.39; 95%CI 1.20-1.62), but without meaningfully, increased risk of hospitalisation/surgery for UC or CD patients. Extending follow-up showed persistence, but attenuation, of all effects. CONCLUSIONS: Initiation of PPIs or H2Ra may be associated with short-term changes in the course of IBD. Although confounding by indication was adjusted using propensity score matching, residual confounding may persist and findings need to be interpreted cautiously.

Antiulcer potential of the ethanolic extract of Aerva persica Merrill root in rats.

The ethanol extract of the roots of Aerva persica (Burm f) Merrill (Amaranthaceae) was investigated to determine its antiulcer and in vivo antioxidant activities in albino Wistar rats. Ulcers were induced by ethanol and pylorus ligation. The extract was administered at the dose of 200mg/kg orally, p.o. for 15 consecutive days. The ulcer index of the ethanol extract was found to be significantly reduced compared with control animals. The effect was also assessed by determining the free acidity, pepsin activity, total carbohydrate (TC), and protein content (PK) in control, standard, and test group animals. The in vivo antioxidant activity was evaluated by determining the reduced glutathione level (GSH) and malondialdehyde (MDA) level in the tissue homogenates. The results reveal the significant reduction in the level of malondialdehyde and the increase in the level of reduced glutathione in the rats that received the ethanolic extract. Furthermore, histopathological studies have shown that pretreatment with the ethanolic extract of the roots of A persica reduces (100%) ethanol- and pylorus ligation-induced hemorrhagic necrosis in rats.

Reducing carcinogenic acetaldehyde exposure in the achlorhydric stomach with cysteine.

BACKGROUND: Acetaldehyde, associated with alcohol consumption, has recently been classified as a group 1 carcinogen in humans. Achlorhydric atrophic gastritis is a well-known risk factor for gastric cancer. Achlorhydria leads to microbial colonization of the stomach. Several of these microbes are able to produce significant amounts of acetaldehyde by oxidation from alcohol. Acetaldehyde can be eliminated from saliva after alcohol intake and during smoking with a semi-essential amino acid, L-cysteine. The aim of this study was to determine whether cysteine can be used to bind acetaldehyde in the achlorhydric stomach after ethanol ingestion. METHODS: Seven volunteers with achlorhydric atrophic gastritis were given either slow-release L-cysteine or placebo capsules in a double-blinded randomized trial. Volunteers served as their own controls. A naso-gastric tube was inserted to each volunteer. The volunteers ingested placebo or 200 mg of L-cysteine capsules, and ethanol 0.3 g/kg body weight (15 vol%) was infused intragastrically through a naso-gastric tube. Five-milliliter samples of gastric contents were aspirated at 5-minute intervals. RESULTS: During the follow-up period, the mean acetaldehyde level of gastric juice was 2.6 times higher with placebo than with L-cysteine (13 vs. 4.7 µM, p < 0.05, n = 7). CONCLUSIONS: L-cysteine can be used to decrease acetaldehyde concentration in the achlorhydric stomach during alcohol exposure. Intervention studies with L-cysteine are needed on reducing acetaldehyde exposure in this important risk group for gastric cancer.

Nanoparticles incorporated in pH-sensitive hydrogels as amoxicillin delivery for eradication of Helicobacter pylori.

A variety of approaches have been studied to overcome the problems encountered with using antibiotics, which are ineffective in treating Helicobacter pylori infections. In our study, chitosan/poly-gamma-glutamic acid nanoparticles incorporated into pH-sensitive hydrogels were developed as an efficient carrier for amoxicillin delivery. Our results indicate that hydrogels are pH-sensitive, leading to protecting nanoparticles from being destructed by gastric acid. The results of drug releasing in vitro study clearly indicate that the amount of amoxicillin released from nanoparticles incorporated in hydrogels at pH 1.2 was relatively low (14%), compared to that from only nanoparticles (50%). Confocal laser scanning microscopy revealed that nanoparticles could infiltrate cell-cell junctions and interact with H. pylori infection sites in the intercellular spaces. Additionally, the incorporation of amoxicillin-loaded nanoparticles in a hydrogel protected the drug from the actions of the gastric juice and facilitated amoxicillin interaction specifically with intercellular spaces, the site of H. pylori infection.

The impact of proton-pump inhibitors on intraperitoneal sepsis: a word of caution for transgastric NOTES procedures.

BACKGROUND: During transgastric natural orifice transluminal endoscopic surgery (NOTES), there is an iatrogenic perforation of the gastric wall with leakage of gastric contents into the peritoneal cavity. The aim of this study is to determine the effect of proton-pump inhibitors (PPI) and alterations of gastric pH on infection during transgastric surgery. METHODS: Thirty 250-g male Sprague-Dawley rats were divided into a study group (SG, n = 15) and a control group (CG, n =15). SG were given 5 mg/kg pantoprazole for 3 days before procedure and another dose 1 h before. CG received saline at similar time points. A mini-laparotomy with gastrotomy was performed. Aspiration of 2.0 cc gastric contents was removed from the stomach and injected into the peritoneal cavity of both groups. Gastric pH and peritoneal pH levels were obtained. Gastric aspirate was sent for culture. White blood cell counts (WBC) were obtained on postoperative days 1, 7, and 14, and C-reactive protein (CRP) levels were obtained on postoperative day 1. At day 14, a necropsy was performed and aerobic and anaerobic cultures of the peritoneal cavity were obtained. RESULTS: There were no deaths in either group. The average gastric pH in the SG was 5.13 versus 3.26 (p = 0.03) in the CG. The average peritoneal pH was similar in both groups. The WBC in the SG was 4.5 vs. 3.5 (1,000 cells/mm) in the CG. There was no elevation in CRP levels in either group. Bacterial cultures were positive in 3/15 (20%) rats in the CG and in 9/15 (60%) in the SG (p = 0.008). Intra-abdominal abscesses were found in 2/15 (13%) rats in the CG and in 5/15 (33%) in the SG (p = 0.08). CONCLUSIONS: Pretreatment with a PPI resulted in a higher rate of peritoneal bacterial contamination and abscess formation. The acidic environment of the stomach appears to be protective against infection when intraperitoneal contamination occurs as a result of gastrotomy.