s-1743 and Disease-Models--Animal

Preeclampsia is a devastating, multisystem disorder of pregnancy. It has no cure except delivery, which if premature can impart significant neonatal morbidity. Efforts to repurpose pregnancy-safe therapeutics for the treatment of preeclampsia have led to the assessment of the proton pump inhibitor, esomeprazole. Preclinically, esomeprazole reduced placental secretion of anti-angiogenic sFlt-1, improved endothelial dysfunction, promoted vasorelaxation, and reduced maternal hypertension in a mouse model. Our understanding of the precise mechanisms through which esomeprazole works to reduce endothelial dysfunction and enhance vasoreactivity is limited. Evidence from earlier studies suggested esomeprazole might work via the nitric oxide pathway, upregulating endothelial nitric oxide synthase (eNOS). Here, we investigated the effect of esomeprazole in a mouse model of L-NAME-induced hypertension (decreased eNOS activity). We further antagonised the model by addition of diet-induced obesity, which is relevant to both preeclampsia and the nitric oxide pathway. Esomeprazole did not decrease blood pressure in this model, nor were there any alterations in vasoreactivity or changes in foetal outcomes in lean mice. We observed similar findings in the obese mouse cohort, except esomeprazole treatment enhanced ex vivo acetylcholine-induced vasorelaxation. As acetylcholine induces nitric oxide production, these findings hint at a function for esomeprazole in the nitric oxide pathway.

Topics: Acetylcholine; Animals; Disease Models, Animal; Esomeprazole; Female; Humans; Hypertension; Mice; Mice, Obese; Nitric Oxide; Nitric Oxide Synthase Type III; Obesity; Placenta; Pre-Eclampsia; Pregnancy

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease of unknown etiology. Currently, pirfenidone and nintedanib are the only FDA-approved drugs for the treatment of IPF and are now the standard of care. This is a significant step in slowing down the progression of the disease. However, the drugs are unable to stop or reverse established fibrosis. Several retrospective clinical studies indicate that proton pump inhibitors (PPIs; FDA-approved to treat gastroesophageal reflux) are associated with favorable outcomes in patients with IPF, and emerging preclinical studies report that PPIs possess antifibrotic activity. In this study, we evaluated the antifibrotic efficacy of the PPI esomeprazole when combined with pirfenidone in vitro and in vivo. In cell culture studies of IPF lung fibroblasts, we assessed the effect of the combination on several fibrosis-related biological processes including TGFβ-induced cell proliferation, cell migration, cell contraction, and collagen production. In an in vivo study, we used mouse model of TGFβ-induced lung fibrosis to evaluate the antifibrotic efficacy of esomeprazole/pirfenidone combination. We also performed computational studies to understand the molecular mechanisms by which esomeprazole and/or pirfenidone regulate lung fibrosis. We found that esomeprazole significantly enhanced the anti-proliferative effect of pirfenidone and favorably modulated TGFβ-induced cell migration and contraction of collagen gels. We also found that the combination significantly suppressed collagen production in response to TGFβ in comparison to pirfenidone monotherapy. In addition, our animal study demonstrated that the combination therapy effectively inhibited the differentiation of lung fibroblasts into alpha smooth muscle actin (αSMA)-expressing myofibroblasts to attenuate the progression of lung fibrosis. Finally, our bioinformatics study of cells treated with esomeprazole or pirfenidone revealed that the drugs target several extracellular matrix (ECM) related pathways with esomeprazole preferentially targeting collagen family members while pirfenidone targets the keratins. In conclusion, our cell biological, computational, and in vivo studies show that the PPI esomeprazole enhances the antifibrotic efficacy of pirfenidone through complementary molecular mechanisms. This data supports the initiation of prospective clinical studies aimed at repurposing PPIs for the treatment of IPF and other fibrotic lung diseases

Topics: Animals; Disease Models, Animal; Esomeprazole; Idiopathic Pulmonary Fibrosis; Mice; Prospective Studies; Proton Pump Inhibitors; Retrospective Studies; Transforming Growth Factor beta

Radiation therapy is a mainstream strategy in the treatment of several cancer types that are surgically unresectable. Unfortunately, cancer patients often suffer from unintended consequences of radiotherapy, including the development of skin inflammation (dermatitis), which may progress to fibrosis. These morbid complications often require interruption of radiotherapy and threaten the relapse of underlying cancer. Current treatment options for radiation dermatitis are suboptimal and compel the need to develop safer, more effective therapies. In this study, we assessed the biophysical properties of topically-formulated esomeprazole (here referred to as dermaprazole) and performed proof-of-concept studies to evaluate its efficacy

Topics: Active Transport, Cell Nucleus; Administration, Topical; Animals; Anti-Inflammatory Agents; Disease Models, Animal; Esomeprazole; Fibrosis; Gene Expression Profiling; Heme Oxygenase-1; Humans; Inflammation; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Models, Anatomic; NF-E2-Related Factor 2; Radiodermatitis; Radiotherapy; Skin; Wound Healing

The central nervous system (CNS) and gastrointestinal tract (GIT) are linked through neuro-endocrine and humoral pathways. Critically ill patients suffer severe physical and emotional stress and frequently receive acid suppressants; however, stress and acid suppression may alter GIT microbiota. This study evaluated the effects of acid suppression on the GIT microbiota and genome-wide expression of brain-specific genes in a murine model of restraint stress. Twenty-four male C57BL/6J mice were randomly assigned to three days of restraint stress by hypothermic immobilization or control environment for three hours daily and either esomeprazole 2 mg/kg or saline by intraperitoneal injection daily. Bacterial communities associated with the stomach, ileum, cecum, and mid-colon were determined by broad-range 16S rRNA gene sequencing, while RNA-sequencing assessed mRNA expression in the hippocampus. Both stress (p < 0.001) and esomeprazole (p = 0.006) had significant, independent effects on the composition of stomach microbiota. Stress had no impact on the hippocampus but the addition of esomeprazole induced differential expression of 124 genes, many of which are involved in cognitive and behavior pathways. Gene expression was correlated with the abundances of multiple microbial families. Acute stress has region-specific effects on the distribution of GIT commensal bacteria which is heightened with acid suppression. Several key biological processes in the hippocampus that are needed for neurocognition are affected by dysbiosis caused by acid suppression during stress. Further studies should evaluate associations between microbiota, host gene expression, the abundance of CNS neurocognitive modulators, and their impact on cognition and behavior.

Topics: Animals; Disease Models, Animal; Esomeprazole; Gastrointestinal Microbiome; Gene Expression; Hippocampus; Male; Mice, Inbred C57BL; Proton Pump Inhibitors; Random Allocation; Restraint, Physical; RNA, Bacterial; RNA, Messenger; RNA, Ribosomal, 16S; Stress, Psychological

Gastric ulcer is a common problem affecting the gastrointestinal tract. Spirulina and wheatgrass are natural substances that have anti-inflammatory and antioxidant effects. The aim of the Work was to elucidate the possible protective role of spirulina and wheatgrass versus standard treatment esomeprazole on indomethacin-induced gastric ulcer in adult male albino rats. Eighty adult male albino rats were divided into eight groups: group I (the control group), group II that received indomethacin (100 mg/kg orally), group III that received esomeprazole (20 mg/kg orally), group IV that received spirulina (1000 mg/kg orally), group V that received wheatgrass (1000 mg/kg orally), group VI that received indomethacin (100 mg/kg) + esomeprazole (20 mg/kg), group VII that received indomethacin (100 mg/kg) + spirulina (1000 mg/kg) and group VIII that received indomethacin (100 mg/kg) + wheatgrass (1000 mg/kg). Six hours after indomethacin treatment, all rats were anesthetized and their stomachs obtained for measures of gastric acidity, pepsin activity, mucin content, gastrin, ulcer index, total antioxidant capacity (TAC), tumor necrosis factor -α (TNF-α), interleukin-8 (IL8), proapoptotic protein (Bax). Histological (using H&E stain, PAS reaction) and immunohistochemical (using anti Ki67 immunostain) techniques were performed. Western immunoblot analysis for heat shock protein 70 (HSP70) was also done. Moreover, a morphometric study was done for area% of positive immunoreactive cells for Ki67 and optical density and area% of PAS reaction. All performed measurements were followed by statistical analysis. Indomethacin induced loss of normal architecture of gastric mucosa with sloughing of surface epithelium and inflammatory cellular infiltration. It also led to a significant increase in gastric acidity, inflammatory mediators (TNF-α, IL-8), pro-apoptotic protein Bax and a significant decrease in TAC levels and HSP-70 expression. There was also a significant decrease in area% of Ki67 immunoreactivity and area% and optical density of PAS reaction as compared with the control group and other pre-treated rats. These disturbed parameters were associated with increased ulcer index. In pre-treatment groups, the structure of the mucosa was similar to control with marked improvement in the biochemical assay. In conclusion, Spirulina and wheatgrass can partly protect the gastric mucosa against indomethacin-induced damage to a degree similar to that of the classical treatment eso

Topics: Animals; Antioxidants; Biomarkers; Biopsy; Cytokines; Disease Models, Animal; Esomeprazole; Immunohistochemistry; Indomethacin; Inflammation Mediators; Male; Phenotype; Plant Extracts; Poaceae; Protective Agents; Rats; Spirulina; Stomach Ulcer

Preeclampsia represents a major complication of pregnancy, associated with greater maternal and fetal complications. We compared the effects of esomeprazole (a proton pump inhibitor) and magnesium sulfate (MgSO4) on the deleterious effects observed on the mother and neonates in experimentally induced preeclampsia in rats.. Preeclampsia was induced in pregnant rats with NG-nitro-l-arginine methyl ester (L-NAME) starting from day 10-till end of pregnancy. Pregnant rats were divided into four groups: control pregnant; untreated preeclampsia; preeclamptic rats treated with MgSO4 and preeclamptic treated with esomeprazole. Treatment was started on day 14 and continued until end of pregnancy. Systolic blood pressure, gestation duration, the total number of pups/fetal resorption, pups birth weight, and histopathology examination of the pup's organs were recorded.. In comparison with the L-NAME group, the MgSO4 and esomeprazole treatment reduced the values of systolic blood pressure; MgSO4 normalized gestational duration while esomeprazole prolonged it (post-term pregnancy); both restored number of delivered pups; with no statistical differences between the numbers of died pups between the four groups studied while with esomeprazole, out of 10 pregnant females, 2 of them had complete intrauterine fetal resorption; esomeprazole normalized birth weight and histological structure of fetal liver, kidney, and brain. On the other side, MgSO4 treatment gave rise to lower than normal birth weight and minimal tissue damage.. Esomeprazole and MgSO4 improved systolic blood pressure, prevented preterm labor and restored numbers of pups delivered and fetal weight. Esomeprazole prolonged gestational period post-term with subsequent improving reproductive outcome.

Topics: Animals; Animals, Newborn; Birth Weight; Blood Pressure; Disease Models, Animal; Esomeprazole; Female; Fetal Weight; Litter Size; Magnesium Sulfate; NG-Nitroarginine Methyl Ester; Pre-Eclampsia; Pregnancy; Rats; Rats, Sprague-Dawley

Spondias mombin Linn (Anacardiaceae) and Ficus exasperata Valh (Moraceae) are botanicals with known phytotherapeutic potentials in the traditional system of medicine in the world.. The objective of this study is to investigate the quantitative polyphenolic constituents and gastroprotective effects of aqueous leaf extracts of Spondias mombin and Ficus exasperata against indomethacin-induced gastric ulcer in rats.. Ulceration was induced by a single oral administration of indomethacin (30 mg/kg body weight (b.w.)). Ulcerated rats were orally administered with esomeprazole (a reference drug) at a dose of 20 mg/kg body weight, and Spondias mombin and Ficus exasperata at a dose of 100 and 200 mg/kg b.w. once daily for 21 d after ulcer induction. Gastric secretions and antioxidant parameters were thereafter evaluated.. The significantly increased (p < 0.05) ulcer index, gastric volume, malondialdehyde level, and pepsin activity by indomethacin were effectively reduced by 65.40, 36.47, 45.71, and 53.79%, respectively, following treatment with F. exasperata at 200 mg/kg b.w. S. mombin at this regimen also attenuated these parameters by 71.70, 46.62, 50.16, and 55.73%. Moreover, the extracts significantly increase the reduced activity of superoxide dismutase as well as pH and mucin content in the ulcerated rats.. These findings are indicative of gastroprotective and antioxidative potentials of the extracts which is also evident in the degree of % inhibition against ulceration. The available data in this study suggest that the extracts proved to be capable of ameliorating indomethacin-induced gastric ulceration and the probable mechanisms are via antioxidative and proton pump inhibition.

Topics: Anacardiaceae; Animals; Anti-Ulcer Agents; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Esomeprazole; Ficus; Gastric Mucosa; Hydrogen-Ion Concentration; Indomethacin; Malondialdehyde; Mucins; Pepsin A; Phytotherapy; Plant Extracts; Plant Leaves; Plants, Medicinal; Proton Pump Inhibitors; Rats, Wistar; Stomach Ulcer; Superoxide Dismutase; Time Factors

Clostridium difficile is currently the leading cause of infectious diarrhea in hospitalized patients. In addition to the infection due to toxigenic C. difficile in the gastrointestinal tract of susceptible hosts, other predisposing factors for C. difficile infection (CDI) are identified, including advanced age, a prolonged hospital stay, and use of acid-suppressive drugs. Of note, exposure to gastric acid-reducing agents, such as H2 blockers and proton pump inhibitors (PPIs), remains a controversial risk factor, and has been associated with CDI in some studies but not in others. A mouse model of antibiotic-associated clostridial colitis was established to examine the role of PPIs for CDI.. A mouse model of antibiotic-associated clostridial colitis was set up. NF-κB reporter mice were used to address the in vivo spatial and temporal inflammatory patterns of C. difficile-associated colitis. Serum levels of lipopolysaccharide and dextran-FITC were measured to reflect the barrier permeability of affected intestines.. Mice with CDI that were exposed to PPI exhibited greater losses of stool consistency and body and cecal weights than those that were not exposed to PPI. Further, more neutrophilic infiltrations, epithelial damage, and inflammatory cytokine expression were noted in colon specimens of the mice with PPI exposure. More-evident inflammatory responses were detected by in vivo imaging of NF-κB reporter mice with CDI that were exposed to PPI. Gut barrier permeability was increased to a greater extent, as reflected by higher serum levels of lipopolysaccharide and dextran-FITC in mice with CDI that were exposed to PPI.. Our mouse model demonstrates that PPI exposure increases the severity of intestinal inflammation in mice with C. difficile-associated colitis.

Topics: Animals; Anti-Bacterial Agents; Clostridioides difficile; Colon; Cytokines; Disease Models, Animal; Enterocolitis, Pseudomembranous; Esomeprazole; Feces; Gene Expression Regulation, Bacterial; Genes, Reporter; Goblet Cells; Mice; NF-kappa B; Proton Pump Inhibitors; Up-Regulation

The beneficial outcome associated with the use of proton pump inhibitors (PPIs) in idiopathic pulmonary fibrosis (IPF) has been reported in retrospective studies. To date, no prospective study has been conducted to confirm these outcomes. In addition, the potential mechanism by which PPIs improve measures of lung function and/or transplant-free survival in IPF has not been elucidated.. Here, we used biochemical, cell biological and preclinical studies to evaluate regulation of markers associated with inflammation and fibrosis. In our in vitro studies, we exposed primary lung fibroblasts, epithelial and endothelial cells to ionizing radiation or bleomycin; stimuli typically used to induce inflammation and fibrosis. In addition, we cultured lung fibroblasts from IPF patients and studied the effect of esomeprazole on collagen release. Our preclinical study tested efficacy of esomeprazole in a rat model of bleomycin-induced lung injury. Furthermore, we performed retrospective analysis of interstitial lung disease (ILD) databases to examine the effect of PPIs on transplant-free survival.. The cell culture studies revealed that esomeprazole controls inflammation by suppressing the expression of pro-inflammatory molecules including vascular cell adhesion molecule-1, inducible nitric oxide synthase, tumor necrosis factor-alpha (TNF-α) and interleukins (IL-1β and IL-6). The antioxidant effect is associated with strong induction of the stress-inducible cytoprotective protein heme oxygenase-1 (HO1) and the antifibrotic effect is associated with potent inhibition of fibroblast proliferation as well as downregulation of profibrotic proteins including receptors for transforming growth factor β (TGFβ), fibronectin and matrix metalloproteinases (MMPs). Furthermore, esomeprazole showed robust effect in mitigating the inflammatory and fibrotic responses in a murine model of acute lung injury. Finally, retrospective analysis of two ILD databases was performed to assess the effect of PPIs on transplant-free survival in IPF patients. Intriguingly, this data demonstrated that IPF patients on PPIs had prolonged survival over controls (median survival of 3.4 vs 2 years).. Overall, these data indicate the possibility that PPIs may have protective function in IPF by directly modulating the disease process and suggest that they may have other clinical utility in the treatment of extra-intestinal diseases characterized by inflammatory and/or fibrotic phases.

Topics: Aged; Animals; Apoptosis; Biomarkers; Bleomycin; Cell Proliferation; Cell Separation; Collagen; Disease Models, Animal; Esomeprazole; Female; Fibroblasts; Gene Expression Regulation; Genetic Pleiotropy; Humans; Idiopathic Pulmonary Fibrosis; Lung; Lung Transplantation; Male; Middle Aged; Pneumonia; Proton Pump Inhibitors; Radiation, Ionizing; Rats, Inbred F344; Solubility; Survival Analysis; Transforming Growth Factor beta

Proton pump inhibitors (PPIs) are gastric acid-suppressing agents widely prescribed for the treatment of gastroesophageal reflux disease. Recently, several studies in patients with acute coronary syndrome have raised the concern that use of PPIs in these patients may increase their risk of major adverse cardiovascular events. The mechanism of this possible adverse effect is not known. Whether the general population might also be at risk has not been addressed.. Plasma asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. Elevated plasma ADMA is associated with increased risk for cardiovascular disease, likely because of its attenuation of the vasoprotective effects of endothelial nitric oxide synthase. We find that PPIs elevate plasma ADMA levels and reduce nitric oxide levels and endothelium-dependent vasodilation in a murine model and ex vivo human tissues. PPIs increase ADMA because they bind to and inhibit dimethylarginine dimethylaminohydrolase, the enzyme that degrades ADMA.. We present a plausible biological mechanism to explain the association of PPIs with increased major adverse cardiovascular events in patients with unstable coronary syndromes. Of concern, this adverse mechanism is also likely to extend to the general population using PPIs. This finding compels additional clinical investigations and pharmacovigilance directed toward understanding the cardiovascular risk associated with the use of the PPIs in the general population.

Topics: Amidohydrolases; Animals; Arginine; Biomarkers; Cardiovascular Diseases; Cells, Cultured; Disease Models, Animal; Endothelium, Vascular; Esomeprazole; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type III; Proton Pump Inhibitors; Risk Factors; Vasodilation

Proton pump inhibitors promote ulcer repair in nonsteroidal anti-inflammatory drug (NSAID)-treated patients with ongoing NSAID-induced gastric toxicity, although the underlying mechanisms remain unclear. We examined the healing mechanisms of esomeprazole on NSAID-induced gastric ulcerations in the presence of a continued NSAID treatment. Ulcerations were induced in rats by oral indomethacin (6μmol/kg/day) for 14 days. Indomethacin administration was continued, alone or combined with equivalent acid inhibitory doses of esomeprazole (5μmol/kg/day), lansoprazole (15μmol/kg/day) or famotidine (20μmol/kg/day), for additional 7 days. Stomachs were then processed for: histomorphometric analysis of mucosal injury; mucosal levels of prostaglandin E(2) (PGE(2)) and malondialdehyde (MDA); expression of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), caspase-3, and cyclooxygenase-2 (COX-2) (Western blot); expression of Ki-67 (immunohistochemistry). Indomethacin for 14 days elicited mucosal damage, reduced PGE(2) levels and increased MDA. After additional 7 days, indomethacin induced the following effects: further enhancement of mucosal damage and MDA content; decrease in PGE(2) levels; increase in COX-2 and activated caspase-3 expression; decrease in VEGF, PCNA and Ki-67 expression. In the presence of indomethacin, esomeprazole and lansoprazole were more effective than famotidine in promoting resolution of mucosal damage. Concomitantly, esomeprazole and lansoprazole, but not famotidine, restored PCNA and Ki-67 expression, and normalized MDA levels. Moreover, esomeprazole, lansoprazole and famotidine partly counteracted caspase-3 activation, without affecting VEGF expression. The healing activity of esomeprazole on indomethacin-induced gastric ulcerations can be ascribed to two mechanisms: (1) acid-dependent reduction of pro-apoptotic signalling; (2) acid-independent restoration of proliferating/repairing pathways.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Apoptosis; Blotting, Western; Caspase 3; Cell Proliferation; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Esomeprazole; Famotidine; Gastric Acid; Gastric Mucosa; Histamine H2 Antagonists; Immunohistochemistry; Indomethacin; Ki-67 Antigen; Lansoprazole; Male; Malondialdehyde; Proliferating Cell Nuclear Antigen; Proton Pump Inhibitors; Rats; Rats, Wistar; Stomach Ulcer; Time Factors; Vascular Endothelial Growth Factor A; Wound Healing

The efficacy of proton pump inhibitors in patients at high risk of gastrointestinal injury receiving non-steroidal anti-inflammatory drugs is currently debated.. To evaluate the effects of esomeprazole on the impairment of gastric ulcer healing associated with non-steroidal anti-inflammatory drug treatment.. Gastric ulcers were induced in rats by acetic acid. Four days later, animals were treated daily with equivalent acid-inhibiting doses of esomeprazole or famotidine, alone or in combination with indomethacin. At day 3 or 7 of treatment, ulcerated tissues were processed to assess: ulcer area; malondialdehyde; prostaglandin E(2); nuclear factor-kB; proliferating cell nuclear antigen and caspase-3 (Western blot).. In indomethacin-treated animals, esomeprazole was more effective than famotidine or the antioxidant melatonin in promoting ulcer healing. Malondialdehyde levels were increased by indomethacin, and this effect was counteracted by esomeprazole, but not famotidine. Esomeprazole and famotidine, given alone or in combination with indomethacin, increased proliferating cell nuclear antigen expression. Increased levels of prostaglandin E(2) were detected in ulcerated tissues. Ulcer prostaglandin E(2) production was reduced by indomethacin, alone or in combination with esomeprazole or famotidine, while it was enhanced when esomeprazole or famotidine were tested alone. The activation of caspase-3 was induced by indomethacin, and this effect was prevented by esomeprazole, but not famotidine. In the presence of indomethacin, esomeprazole, but not famotidine, enhanced nuclear factor-kB activation in gastric ulcers.. Esomeprazole counteracts the detrimental action of indomethacin on ulcer repair through both acid-dependent and acid-independent effects. The acid-independent actions are related to decrease in tissue oxidation and apoptosis and to enhancement of nuclear factor-kB activation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Antioxidants; Caspase 3; Dinoprostone; Disease Models, Animal; Esomeprazole; Famotidine; Indomethacin; Male; Malondialdehyde; Melatonin; NF-kappa B; Proliferating Cell Nuclear Antigen; Rats; Rats, Wistar; Stomach Ulcer; Treatment Outcome; Wound Healing

To evaluate measurements of intragastric pH with the Bravo capsule system over a prolonged time.. A Bravo capsule was placed inside the rat gastric body and pH was studied for periods up to five consecutive days. For comparison, a gastric fistula model was used. Effects of ghrelin and esomeprazole, with or without pentagastrin, on gastric pH were studied. In addition, effects of esomeprazole on plasma ghrelin, gastrin and somatostatin were analyzed.. All rats recovered after surgery. The average 24-h pH during free feeding was 2.3 +/- 0.1 (n = 20) with a variation of 18% +/- 6% over 5 d. Ghrelin, 2400 pmol/kg, t.i.d. increased pH from 1.7 +/- 0.1 to 3.1 +/- 0.3 (P < 0.01) as recorded with the Bravo system. After esomeprazole (1 mg/kg, 3 mg/kg and 5 mg/kg) there was a dose-dependent pH increase of maximally 3.4 +/- 0.1, with day-to-day variation over the entire period of 8% +/- 3%. The fistula and pH studies generated similar results. Acid inhibition with esomeprazole increased plasma ghrelin from 10 +/- 2 pmol/L to 65 +/- 26 pmol/L (P < 0.001), and somatostatin from 10 +/- 2 pmol/L to 67 +/- 18 pmol/L (P < 0.001).. pH measurements with the Bravo capsule are reliable, and comparable to those of the gastric fistula model. The Bravo system optimizes accurate intragastric pH monitoring over prolonged periods and allows both short- and long-term evaluation of effects of drugs and hormones.

Topics: Animals; Capsule Endoscopes; Capsule Endoscopy; Disease Models, Animal; Esomeprazole; Gastric Acid; Gastric Acidity Determination; Gastric Fistula; Gastric Mucosa; Gastrins; Gastrointestinal Agents; Gastrointestinal Hormones; Ghrelin; Hydrogen-Ion Concentration; Male; Monitoring, Ambulatory; Pentagastrin; Proton Pump Inhibitors; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Somatostatin; Telemetry; Time Factors