-
Journal of Veterinary Internal Medicine May 2017Esomeprazole is an S-enantiomer of omeprazole that has favorable pharmacokinetics and efficacious acid suppressant properties in humans. However, the pharmacokinetics... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Esomeprazole is an S-enantiomer of omeprazole that has favorable pharmacokinetics and efficacious acid suppressant properties in humans. However, the pharmacokinetics and effects on intragastric pH of esomeprazole in dogs have not been reported.
OBJECTIVE
To determine the pharmacokinetics of esomeprazole administered via various routes (PK study) and to investigate the effect of esomeprazole on intragastric pH with a Bravo pH monitoring system (PD study).
ANIMALS
Seven adult male Beagle dogs and 5 adult male Beagle dogs were used for PK and PD study, respectively.
METHODS
Both studies used an open, randomized, and crossover design. In the PK study, 7 dogs received intravenous (IV), subcutaneous (SC), and oral doses (PO) of esomeprazole (1 mg/kg). Each treatment period was separated by a washout period of at least 10 days. Esomeprazole plasma concentrations were measured by HPLC/MS/MS. In the efficacy study, intragastric pH was recorded without medication (baseline pH) and following IV, SC, and PO esomeprazole dosing regimens (1 mg/kg) in 5 dogs.
RESULTS
The bioavailability of esomeprazole administered as PO enteric-coated granules and as SC injections was 71.4 and 106%, respectively. The half-life was approximately 1 hour. Mean ± SD percent time intragastric pH was ≥3 and ≥4 was 58.9 ± 21.1% and 40.9 ± 17.3% for IV group, 75.8 ± 16.4% and 62.7 ± 17.7% for SC group, 88.2 ± 8.9% and 82.5 ± 7.7% for PO group, and 12.5 ± 3.6% and 3.7 ± 1.8% for baseline. The mean percent time with intragastric pH was ≥3 or ≥4 was significantly increased regardless of the dosing route (P < .05).
CONCLUSION
The PK parameters for PO and SC esomeprazole administration were favorable, and esomeprazole significantly increased intragastric pH after IV, PO, and SC administration. IV and SC administration of esomeprazole might be useful when PO administration is not possible. No significant adverse effects were observed.
Topics: Administration, Oral; Animals; Anti-Ulcer Agents; Area Under Curve; Cross-Over Studies; Dogs; Esomeprazole; Esophagus; Female; Hydrogen-Ion Concentration; Injections, Intravenous; Injections, Subcutaneous; Male; Reference Values
PubMed: 28407418
DOI: 10.1111/jvim.14713 -
BMC Complementary and Alternative... Jan 2008The present study was undertaken to evaluate the potential of the rhizomes of the Indian medicinal plant, Picrorhiza kurroa in healing indomethacin-induced acute stomach...
BACKGROUND
The present study was undertaken to evaluate the potential of the rhizomes of the Indian medicinal plant, Picrorhiza kurroa in healing indomethacin-induced acute stomach ulceration in mice and examine its capacity to modulate oxidative stress and the levels of prostaglandin (PGE2) and EGF during the process.
METHODS
Male swiss albino mice, ulcerated with indomethacin (18 mg/kg, p. o., single dose) were treated up to 7 days with different doses of the methanol extract of P. kurroa rhizomes (designated as PK). The healing capacity of the most effective dose of PK (20 mg/kg, p. o. x 3 d) was compared with that of omeprazole (Omez) (3 mg/kg, p. o. x 3 d). The effects of the drug-treatment for one and three days on the biochemical parameters were assessed by comparing the results with that of untreated mice of the 1st and 3rd day of ulceration. The stomach tissues of the mice were used for the biochemical analysis.
RESULTS
The macroscopic indices revealed maximum ulceration on the 3rd day after indomethacin administration, which was effectively healed by PK. Under the optimized treatment regime, PK and Omez reduced the ulcer indices by 45.1% (P < 0.01), and 76.3% respectively (P < 0.001), compared to the untreated ulcerated mice. Compared to the ulcerated untreated mice, those treated with PK for 3 days showed decreased the levels of thiobarbituric acid reactive substances (TBARS) (32.7%, P < 0.05) and protein carbonyl (37.7%, P < 0.001), and increased mucin (42.2%, P < 0.01), mucosal PGE2 (21.4%, P < 0.05), and expressions of COX-1 and 2 (26.9% and 18.5%, P < 0.05), EGF (149.0%, P < 0.001) and VEGF (56.9%, P < 0.01). Omez reduced the TBARS (29.4%, P < 0.05), and protein carbonyl (38.9%, P < 0.001), and increased mucin (38.3%, P < 0.01), without altering the other parameters significantly.
CONCLUSION
PK (20 mg/kg, p. o. x 3 days) could effectively heal indomethacin-induced stomach ulceration in mice by reducing oxidative stress, and promoting mucin secretion, prostaglandin synthesis and augmenting expressions of cyclooxygenase enzymes and growth factors.
Topics: Administration, Oral; Animals; Anti-Ulcer Agents; Dinoprostone; Dose-Response Relationship, Drug; Epidermal Growth Factor; Gastric Mucosa; Indomethacin; Male; Mice; Oxidative Stress; Phytotherapy; Picrorhiza; Plant Extracts; Rhizome; Stomach; Stomach Ulcer; Thiobarbituric Acid Reactive Substances
PubMed: 18237397
DOI: 10.1186/1472-6882-8-3 -
African Journal of Traditional,... 2014There are strong beliefs in the efficacy of traditional medical systems worldwide. Many herbs have been acclaimed to possess antiulcer effects and could be unexplored...
BACKGROUND
There are strong beliefs in the efficacy of traditional medical systems worldwide. Many herbs have been acclaimed to possess antiulcer effects and could be unexplored sources of new lead compounds. Sida corymbosa R. E. Fries (Malvaceae) is used in Northern Nigeria to treat ulcers and wounds. This work aimed to investigate the usefulness of Sida corymbosa in treatments of stomach ulcers and wounds in traditional medicine.
MATERIALS AND METHODS
Effect of the aqueous extract was determined on gastric ulceration, rate of wound healing and inflammation using ethanol-induced and diclofenac-induced ulceration, wound excision model and albumin-induced inflammation respectively in rats.
RESULTS
The study demonstrated the anti-ulcer activity of Sida corymbosa as the extract (250, 500 and 1000 mg/kg) showed a dose-dependent, significant (P<0.05) reduction of ulcer indices against gastric ulcers induced by both ethanol and diclofenac. Topical application of a formulation prepared with the extract of Sida corymbosa on surgically created incisions produced an increase in the rate of healing of the wounds. The extract of Sida corymbosa exhibited a significant (P < 0.05), dose-related decrease in inflammation induced by fresh egg albumin. This study showed that Sida corymbosa has constituents with the ability to reduce the severity of haemorrhagic gastric lesions, promote wound healing and reduce inflammation. These actions may be attributed to any one of the active constituents or as a result of synergistic effects of these phytoconstituents.
CONCLUSION
This study validates the use of the plant in traditional medicine for the treatment of stomach ulcers and wounds.
Topics: Animals; Anti-Inflammatory Agents; Anti-Ulcer Agents; Diclofenac; Dose-Response Relationship, Drug; Ethanol; Inflammation; Malvaceae; Medicine, African Traditional; Ovalbumin; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Stomach Ulcer; Wound Healing; Wounds, Penetrating
PubMed: 24653558
DOI: No ID Found -
Nutrients Mar 2023L. and black seeds are traditionally used for cooking and medicinal purposes in Arab and other countries. Although seed extract has many known biological effects, the...
L. and black seeds are traditionally used for cooking and medicinal purposes in Arab and other countries. Although seed extract has many known biological effects, the biological effects of cold-pressed oil are poorly understood. Therefore, the objective of this study was to investigate the gastroprotective effects and subacute oral toxicity of black seed oil (BSO) in an animal model. The gastroprotective effects of oral BSO (50% and 100%; 1 mg/kg) were tested using acute experimental models of ethanol-induced gastric ulcers. Gross and histological gastric lesions, ulcerated gastric areas, ulcer index score, percentage of inhibition rate, gastric juice pH, and gastric wall mucus were all evaluated. The subacute toxicity of BSO and its thymoquinone (TQ) content were also examined. The results indicated that the administration of BSO exerted gastroprotective effects by increasing the gastric wall mucus and decreasing gastric juice acidity. In the subacute toxicity test, the animals behaved normally, and their weight and water and food intake did not show significant variations. High-performance liquid chromatography detected 7.3 mg/mL TQ in BSO. These findings suggest that BSO may be a safe therapeutic drug for preventing gastric ulcers.
Topics: Rats; Animals; Stomach Ulcer; Ethanol; Nigella sativa; Rats, Wistar; Gastric Mucosa; Plant Extracts; Anti-Ulcer Agents
PubMed: 36986262
DOI: 10.3390/nu15061532 -
Pharmaceutical Biology Dec 2022Zuojin Pill (ZJP) has been used to treat gastrointestinal problems in China for hundreds of years.
CONTEXT
Zuojin Pill (ZJP) has been used to treat gastrointestinal problems in China for hundreds of years.
OBJECTIVE
To discover more potential active ingredients and evaluate the gastroprotective mechanisms of ZJP.
MATERIALS AND METHODS
An approach involving UPLC-Q-Orbitrap HRMS and serum pharmacochemistry was established to screen the multiple chemical constituents of ZJP. Male Sprague-Dawley (SD) rats were divided into six groups: normal control, ulcer control, omeprazole (30 mg/kg), and three ZJP groups (1.0, 2.0 and 4.0 g/kg). After oral treatment with ZJP or omeprazole for 7 days, all groups except the normal control group were orally administered 5 mL/kg ethanol to induce gastric ulceration. Histopathological assessment of gastric tissue was performed by haematoxylin and eosin staining. Antioxidant parameters and inflammatory mediators were determined using ELISA Kit and immunohistochemical analysis.
RESULTS
Ninety components were identified in ZJP. Among them, 23 prototypes were found in rat serum after oral administration of ZJP. The ulcer inhibition was over 90.0% for all the ZJP groups. Compared with the ulcer control rats, ZJP (4.0 g/kg) enhanced the antioxidant capacity of gastric tissue: superoxide dismutase (1.33-fold), catalase (2.61-fold), glutathione (2.14-fold), and reduced the malondialdehyde level (0.48-fold). Simultaneously, the ZJP meaningfully lowered the content of tumour necrosis factor-α (0.76-fold), interleukin-6 (0.66-fold), myeloperoxidase (0.21-fold), and nuclear factor kappa B (p65) (0.62-fold).
DISCUSSION AND CONCLUSIONS
This study showed ZJP could mitigate ethanol-induced rat gastric ulcers, which might benefit from the synergistic actions of multiple ingredients. The findings could support the quality control and clinical trials of ZJP.
Topics: Animals; Anti-Ulcer Agents; Antioxidants; Drugs, Chinese Herbal; Ethanol; Gastric Mucosa; Male; Omeprazole; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Superoxide Dismutase; Ulcer
PubMed: 35938492
DOI: 10.1080/13880209.2022.2098345 -
Journal of Ethnopharmacology Oct 2010Abarema cochliacarpos (Gomes) Barneby & Grimes (Mimosaceae) is a species--in folk medicine of Lagarto city, Sergipe state, northeastern Brazil--reputed to heal gastric...
ETHNOPHARMACOLOGICAL RELEVANCE
Abarema cochliacarpos (Gomes) Barneby & Grimes (Mimosaceae) is a species--in folk medicine of Lagarto city, Sergipe state, northeastern Brazil--reputed to heal gastric ulcer and gastritis.
AIM OF THE STUDY
Chloroform (CE) and methanolic (ME) extracts as well as ethyl acetate fraction (AF), butanolic fraction (AC) and aqueous fraction (AQF) of the methanolic extract of Abarema cochliacarpos bark were evaluated against acute gastric ulcer. The AC fraction was selected to assess its activity in ulcer healing and its gastroprotective effects via mucus and gastric secretion.
MATERIAL AND METHODS
The gastroprotective action of CE and ME extracts and the fractions of the latter were evaluated in a rodent experimental model. The action mechanisms, involvements of the antisecretory action and mucus production, toxicological and healing activity of the AC (150 mg/kg, p.o.) were evaluated. We also used histological analysis (HE and PAS) and immunohistochemical (PCNA, COX-2, VEGF and HSP-70) assays to evaluate the effects of Abarema cochliacarpos.
RESULTS
CE (200 and 400 mg/kg, p.o.) and ME (100, 200 and 400 mg/kg, p.o.) extracts were able to protect gastric mucosa against absolute ethanol. Respective inhibitions produced were: 65.31% and 83.80% by the first; 91.69%, 96.75% and 99.80% by the second; and 74.24% by the AC fraction. Antisecretory and mucus production effects were exhibited by the AC fraction, which also accelerated the healing of ulcerated gastric mucosa by stimulating proliferation factors (PCNA) and induced healing factors including COX-2, VEGF and HSP-70.
CONCLUSION
All these results suggest that Abarema cochliacarpos (Gomes) Barneby & Grimes presents gastroprotective effects and wound-healing properties.
Topics: Animals; Anti-Ulcer Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Gastric Mucosa; Male; Mice; Plant Bark; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Stomach Ulcer; Toxicity Tests, Acute
PubMed: 20696232
DOI: 10.1016/j.jep.2010.08.001 -
Pharmaceutical Biology Dec 2020Hance (Zingiberaceae) is traditionally used to treat inflammation, pain, colds and digestive diseases. (Comparative Study)
Comparative Study
CONTEXT
Hance (Zingiberaceae) is traditionally used to treat inflammation, pain, colds and digestive diseases.
OBJECTIVE
To investigate the potential protective mechanism of total flavonoids from the rhizomes of (F-AOH) in ethanol-induced acute gastric and .
MATERIALS AND METHODS
: Gastric damage was induced in BALB/c mice by administering ethanol (10 mL/kg) after oral treatment with F-AOH at 126.8, 63.4 and 31.7 mg/kg or ranitidine (Ran) at 100 mg/kg (1 week of continuous gavage). : Gastric mucosal epithelial cells (GES-1) were incubated with F-AOH (8, 4 and 2 μg/mL) for 16 h and treated with 7% ethanol for 4 h. The extent of gastric damage was assessed histopathologically, and the expression of NF-κB, COX-2, TNF-α, iNOS and IL-1β was quantified by Western blot analysis. In addition, proinflammatory mediators and concentrations of motilin (MTL) and gastrin (GAS) were measured by ELISA test.
RESULTS
F-AOH effectively reduced the ulcer index (from 23.4 ± 4.28 to 8.32 ± 1.5) and reduced release of inflammatory mediators (IL-1β, IL-6, TNF-α and PGE2), increased the content of nitric oxide and improved GAS and MTL secretion. The 50% inhibitory concentration (IC) of F-AOH on cell damage was 17 μg/mL. F-AOH increased ethanol-induced cell survival (from 47 to 85%) and inhibited the expression of NF-κB, COX-2, TNF-α, IL-1β and iNOS proteins.
CONCLUSIONS
F-AOH inhibits ethanol-induced gastric mucosal damage, provides a theoretical basis for galangal in the treatment of other causes of GU, and promotes the application of galanga in the treatment of GU.
Topics: Alpinia; Animals; Anti-Ulcer Agents; Cell Line; Dose-Response Relationship, Drug; Ethanol; Female; Flavonoids; Gastric Mucosa; Humans; Mice; Mice, Inbred BALB C; Nitric Oxide; Ranitidine; Rhizome; Stomach Ulcer
PubMed: 32871094
DOI: 10.1080/13880209.2020.1803370 -
Alimentary Pharmacology & Therapeutics Jun 2006Proton pump inhibitors inhibit the gastric H+/K+-ATPase via covalent binding to cysteine residues of the proton pump. All proton pump inhibitors must undergo acid... (Review)
Review
Proton pump inhibitors inhibit the gastric H+/K+-ATPase via covalent binding to cysteine residues of the proton pump. All proton pump inhibitors must undergo acid accumulation in the parietal cell through protonation, followed by activation mediated by a second protonation at the active secretory canaliculus of the parietal cell. The relative ease with which these steps occur with different proton pump inhibitors underlies differences in their rates of activation, which in turn influence the location of covalent binding and the stability of inhibition. Slow activation is associated with binding to a cysteine residue involved in proton transport that is located deep in the membrane. However, this is inaccessible to the endogenous reducing agents responsible for restoring H+/K+-ATPase activity, favouring a longer duration of gastric acid inhibition. Pantoprazole and tenatoprazole, a novel proton pump inhibitor which has an imidazopyridine ring in place of the benzimidazole moiety found in other proton pump inhibitors, are activated more slowly than other proton pump inhibitors but their inhibition is resistant to reversal. In addition, tenatoprazole has a greatly extended plasma half-life in comparison with all other proton pump inhibitors. The chemical and pharmacological characteristics of tenatoprazole give it theoretical advantages over benzimidazole-based proton pump inhibitors that should translate into improved acid control, particularly during the night.
Topics: Antacids; Anti-Ulcer Agents; Gastric Acid; Humans; Parietal Cells, Gastric; Peptic Ulcer; Proton Pump Inhibitors
PubMed: 16700898
DOI: 10.1111/j.1365-2036.2006.02943.x -
Gut May 2002Uninvestigated dyspepsia refers to patients with new or recurrent dyspeptic symptoms in whom no investigations have previously been undertaken. These patients are much... (Review)
Review
Uninvestigated dyspepsia refers to patients with new or recurrent dyspeptic symptoms in whom no investigations have previously been undertaken. These patients are much more likely to present in primary than in secondary care. It is particularly important to be able to offer effective symptom relief to support the explanation, reassurance, and advice provided to patients, and low dose or standard dose proton pump inhibitor therapy appears to offer the most effective approach to empirical therapy of this kind.
Topics: Anti-Ulcer Agents; Dyspepsia; Humans; Omeprazole; Primary Health Care
PubMed: 11953347
DOI: 10.1136/gut.50.suppl_4.iv42 -
Revista Espanola de Enfermedades... Feb 2017To describe how mesalazine (MSZ) is used in our practice in ulcerative colitis (UC), at what dose, and the success rate (regarding adherence to therapy). (Observational Study)
Observational Study
OBJECTIVE
To describe how mesalazine (MSZ) is used in our practice in ulcerative colitis (UC), at what dose, and the success rate (regarding adherence to therapy).
METHODS
Observational, transversal study, including all patients with UC and with MSZ maintenance therapy seen from September 2014 to February 2015 at two IBD units in Spain. Treatment adherence was measured by the Morisky-Green scale.
RESULTS
We included 203 patients (mean MSZ dose: 2.6 ± 1.0 g/d; median of treatment: 19.5 months [IQR: 8-48]). Doses < 2 g/d were used in 15.3% of cases, 2-2.9 g/d doses in 35.0%, 3-3.9 doses in 29.5%, and ≥ 4 g/d doses in the remaining 20.2%. A single daily dose was preferred in 51.2% of cases, two doses in 33.0% and three doses in 15.8%. A different MSZ brand had been previously used in 36.6% of patients. In 134 cases (66%), the maintenance dose had been increased during a flare-up, and in 49 (36.6% of cases) this higher dose had been kept for maintenance (dose ≥ 4 g/d in 36 patients). During the MSZ therapy, 14 patients (6.9%) suffered mild side effects (21.4% altered liver function tests). Therapy adherence was good in 81.8% of cases.
CONCLUSIONS
Half of our UC patients take high MSZ doses (≥ 3 g/d) as maintenance therapy, with acceptable safety and good adherence. Half of all patients take a single daily dose, and one third needed a different commercial brand during therapy. Opting for a higher MSZ maintenance dose is a possible strategy for a satisfactory maintenance therapy.
Topics: Adult; Aged; Anti-Ulcer Agents; Colitis, Ulcerative; Drug Administration Schedule; Female; Humans; Male; Medication Therapy Management; Mesalamine; Middle Aged
PubMed: 28026200
DOI: 10.17235/reed.2016.4620/2016