|
1
|
Nasrullah MZ, Eljaaly K, Neamatallah T, Fahmy UA, Alamoudi AJ, Bakhsh HT, Abdel-Naim AB. Omeprazole Prevents Colistin-Induced Nephrotoxicity in Rats: Emphasis on Oxidative Stress, Inflammation, Apoptosis and Colistin Accumulation in Kidneys. Pharmaceuticals (Basel) 2022; 15:782. [PMID: 35890080 PMCID: PMC9320444 DOI: 10.3390/ph15070782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 06/19/2022] [Accepted: 06/20/2022] [Indexed: 11/17/2022] Open
Abstract
The clinical value of colistin, a polymyxin antibiotic, is limited by its nephrotoxicity. Omeprazole is a commonly prescribed proton pump inhibitor. The current study aimed to evaluate the effects of the concomitant administration of omeprazole on colistin-induced nephrotoxicity in rats. Omeprazole significantly ameliorated colistin nephrotoxicity as evidenced by prevention in the rise in the serum level of creatinine, urea and cystactin C as well as urinary N-acetylglucosamine activity. This was confirmed by histological studies that indicated a decreased incidence of interstitial nephritis, degenerative cortical changes and collagen deposition. This was accompanied by the prevention of oxidative stress as omeprazole significantly inhibited the lipid peroxidation, glutathione depletion and enzymatic exhaustion of superoxide dismutase as well as catalase. Additionally, omeprazole inhibited the expression of interleukin-6 and tumor necrosis factor-α. Further, omeprazole inhibited the colistin-induced rise in Bax and the down-regulation of Bcl2 mRNA expression. An assessment of the serum levels of colistin revealed that omeprazole had no significant impact. However, it was observed that omeprazole significantly inhibited the accumulation of colistin in kidney tissues. In conclusion, omeprazole protects against colistin-induced nephrotoxicity. This can be attributed to, at least partly, omeprazole's anti-oxidant, anti-inflammatory and anti-apoptotic activities in addition to its ability to prevent the toxic accumulation of colistin in kidneys.
Collapse
Affiliation(s)
- Mohammed Z. Nasrullah
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (T.N.); (A.J.A.); (A.B.A.-N.)
| | - Khalid Eljaaly
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (K.E.); (H.T.B.)
| | - Thikryat Neamatallah
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (T.N.); (A.J.A.); (A.B.A.-N.)
| | - Usama A. Fahmy
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Abdulmohsin J. Alamoudi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (T.N.); (A.J.A.); (A.B.A.-N.)
| | - Hussain T. Bakhsh
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (K.E.); (H.T.B.)
| | - Ashraf B. Abdel-Naim
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (T.N.); (A.J.A.); (A.B.A.-N.)
| |
Collapse
|
|
2
|
Spencer A, Quimby JM, Price JM, MacLane S, Hillsman S, Secoura P, Steiner JM, Katherine Tolbert M. Appetite-stimulating effects of once-daily omeprazole in cats with chronic kidney disease: Double-blind, placebo-controlled, randomized, crossover trial. J Vet Intern Med 2021; 35:2705-2712. [PMID: 34590746 PMCID: PMC8692181 DOI: 10.1111/jvim.16268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 09/10/2021] [Accepted: 09/10/2021] [Indexed: 11/30/2022] Open
Abstract
Background Cats with moderate to advanced chronic kidney disease (CKD) often display clinical signs such as vomiting and decreased appetite, and frequently receive omeprazole or other acid suppressants despite a lack of evidence to support their use. Hypothesis/Objectives To evaluate the effect of once‐daily PO omeprazole on appetite in cats with CKD. We hypothesized that omeprazole would improve subjective appetite assessments in cats with CKD. Animals Fourteen client‐owned cats with International Renal Interest Society (IRIS) stage 2 or 3 CKD and hyporexia. Methods Cats were prospectively enrolled in a multi‐institutional, double‐blinded, randomized, crossover study to evaluate the effect of a 14‐day trial of once‐daily PO omeprazole (1 mg/kg) or placebo (lactose gel capsule) on vomiting frequency and appetite. A daily log was completed by the owner during all treatment and rest periods to assess appetite using a subjective, qualitative, and 5‐point scoring system. Mixed model analyses of variance were performed to determine if average daily percentage food consumed or appetite score, as measured by subjective owner assessment, differed between treatments. Results Compared to placebo, a negligible but statistically significant difference in percentage of food consumed was observed between treatments (P = .04) with once‐daily omeprazole treatment resulting in a 2.7% increase in food consumption compared to placebo. No significant difference, however, was found in appetite score, body weight, or serum creatinine concentration between treatments. Conclusions and Clinical Importance Once‐daily omeprazole does not markedly increase appetite in cats with CKD and should not be used as a first‐line treatment in the absence of evidence of gastrointestinal ulceration.
Collapse
Affiliation(s)
- Ashley Spencer
- North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina, USA
| | - Jessica M Quimby
- The Ohio State University, College of Veterinary Medicine, Columbus, Ohio, USA
| | - Josh M Price
- Department of Small Animal Clinical Sciences, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee, USA
| | - Sally MacLane
- Appalachian Animal Hospital, Piney Flats, Tennessee, USA
| | - Shanna Hillsman
- Department of Small Animal Clinical Sciences, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee, USA
| | - Patty Secoura
- North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina, USA
| | - Jörg M Steiner
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA
| | - M Katherine Tolbert
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA
| |
Collapse
|
|
3
|
Vera ME, Mariani ML, Aguilera C, Penissi AB. Effect of a Cytoprotective Dose of Dehydroleucodine, Xanthatin, and 3-Benzyloxymethyl-5 H-furan-2-one on Gastric Mucosal Lesions Induced by Mast Cell Activation. Int J Mol Sci 2021; 22:5983. [PMID: 34205991 PMCID: PMC8198283 DOI: 10.3390/ijms22115983] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/24/2021] [Accepted: 05/29/2021] [Indexed: 01/13/2023] Open
Abstract
The aim of this study was to determine whether the lactones dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one, would be effective in an animal model of gastric ulcer induced by mast cell activation. Rats were divided into ten groups. Treatments were repeated for four days. The degree of gastric erosion was assessed with a scoring system and histological preparations. Gastric mast cell morphology was analyzed by histological procedures. Serum serotonin levels were determined as markers of mast cell activation. Statistical analyses were done using ANOVA and Tukey-Kramer test. We demonstrated that the repeated administration of compound 48/80 results in extensive mucosal lesions in the gastric mucosa and that such lesions occurred in association with mast cell degranulation and a significant increase of serum serotonin. We showed that these lesions were prevented by dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one and that this effect was similar to that obtained with sodium cromoglycate. In conclusion, the results of the present study indicate that the optimal gastric cytoprotective dose of dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one is efficacious in an animal model of gastric ulcer induced by mast cell activation. Our findings suggest that these lactones could be valuable tools for designing novel therapeutic agents for digestive disorders associated with inappropriate mast cell activation.
Collapse
Affiliation(s)
| | | | | | - Alicia Beatriz Penissi
- Instituto de Histología y Embriología “Dr. Mario H. Burgos” (IHEM-CCT Mendoza-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Casilla de Correo 56, 5500 Mendoza, Argentina; (M.E.V.); (M.L.M.); (C.A.)
| |
Collapse
|
|
4
|
A prospective randomized controlled trial of omeprazole for preventing esophageal stricture in grade 2b and 3a corrosive esophageal injuries. Surg Endosc 2020; 35:2759-2764. [PMID: 32556768 DOI: 10.1007/s00464-020-07707-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 06/09/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Esophageal stricture is a significant complication of grade 2b and 3a esophageal injuries and causes much patient suffering. Preventing strictures would be beneficial to patients but there are currently no proven effective drugs. This study aimed to evaluate the effect of omeprazole for preventing esophageal stricture in adults with grade 2b and 3a corrosive esophageal injuries. METHODS This study was an open single-center prospective randomized controlled trial that took place from April 2018 to January 2020. Patients were randomized to standard treatment or 80 mg/day intravenously × 3 days followed by 40 mg/day orally for 4 weeks. They were endoscoped at baseline and 4 weeks post discharge. Strictures were confirmed radiologically. RESULTS 20 patients were enrolled: 15 with grade 2b and five with grade 3a injuries. Standard care and omeprazole groups numbered 10 each. At 1 month, seven and two patients developed strictures in the standard and omeprazole groups, respectively, p = 0.024, for a risk reduction of 71.4%. CONCLUSIONS Omeprazole reduced the risk of short-term developing esophageal strictures following grade 2b and 3a corrosive esophageal injuries. Larger studies are needed to reconfirm this finding. Thai Clinical Trials Registry (TCTR) number TCTR20190504001.
Collapse
|
|
5
|
Risk Factors for Esophageal Stricture in Grade 2b and 3a Corrosive Esophageal Injuries. J Gastrointest Surg 2018; 22:1659-1664. [PMID: 29855871 DOI: 10.1007/s11605-018-3822-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 05/15/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND PURPOSE Publications document the risk of developing esophageal stricture as a sequential complication of esophageal injury grades 2b and 3a. Although there are studies describing the risk factors of post-corrosive stricture, there is limited literature on these factors. The aim of this study was to evaluate the different factors with post-corrosive esophageal stricture and non-stricture groups in endoscopic grades 2b and 3a of corrosive esophageal injuries. METHODS Data were retrospectively analyzed in the patients with esophageal injury grades 2b and 3a between January 2011 and December 2017. RESULTS One hundred ninety-six corrosive ingestion patients were admitted with 32 patients (15.8%) in grade 2b and 12 patients (6.1%) in grade 3a and stricture was developed in 19 patients (61.3%) with grade 2b and in 10 patients (83.3%) with grade 3a. The patients' height of the non-stricture group was greater than that of stricture groups (2b stricture group, 1.58 ± 0.08 m; 2b non-stricture group, 1.66 ± 0.07 m; p < 0.004; 3a stricture group, 1.52 ± 0.09 m; 3a non-stricture group, 1.71 ± 0.02 m; p < 0.001). Omeprazole was more commonly used in the non-stricture than stricture group (26.3% in the 2b stricture group, 69.2% in the 2b non-stricture group, p = 0.017; 50% in the 3a stricture group, 100% in the 3a non-stricture group, 1.71 ± 0.02 m, p = 0.015). CONCLUSIONS The height of patients may help to predict the risks and the prescription of omeprazole may help to minimize the risks of 2b and 3a post-corrosive esophageal stricture.
Collapse
|
|
6
|
Parvan M, Sajjadi SE, Minaiyan M. Protective Effect of Two Extracts of Cydonia oblonga Miller (Quince) Fruits on Gastric Ulcer Induced by Indomethacin in Rats. Int J Prev Med 2017; 8:58. [PMID: 28900537 PMCID: PMC5582508 DOI: 10.4103/ijpvm.ijpvm_124_17] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2017] [Accepted: 04/22/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND In various studies, Cydonia oblonga Miller (quince) has been reported to have many properties such as antioxidant and anti-ulcerative effects. This study has aimed to investigate the protective effects of quince aqueous extract (QAE) and quince hydroalcoholic extract (QHE) on gastric ulcer caused by indomethacin and the relevant macroscopic, histopathology, and biochemical factors in rats. METHODS Ten groups of male Wistar rats, six in each, were used in this study. These groups included: normal (distilled water), control (distilled water + indomethacin), reference (ranitidine or sucralfate + indomethacin), and test groups (QAE or QHE + indomethacin) treated with three increasing doses (200, 500, and 800 mg/kg). Extracts and drugs were given orally to rats 1 h before injecting the indomethacin (25 mg/kg, intraperitoneally). Six hours later, the abdomen of rats was exposed, its pylorus was legated, gastric acid content was extracted, and its pH and the amount of pepsin secreted were measured by Anson method. Then, histopathology indices, ulcer area, ulcer index, and myeloperoxidase (MPO) activity were measured in gastric mucus. RESULTS Both extracts of quince were effective to reduce the acidity of stomach and pepsin activity. Compared to control group, the average of enzyme activity of MPO was significantly declined in all treated groups. Control group had the highest level of gastric ulcer indices including severity, area, and index while the evaluated parameters had decreased in all extract treated groups although it seems that QAE was somewhat more effective. CONCLUSIONS Protective effect of QAE and QHE on gastric ulcer was done by undermining offensive factors including decreasing the secretion of gastric acid and pepsin activity and by strengthening the protective factors of gastric mucus including antioxidant capacity.
Collapse
Affiliation(s)
- Morteza Parvan
- Department of Pharmacology and Toxciology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
| | - Sayed-Ebrahim Sajjadi
- Department of Pharmacognosy, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
| | - Mohsen Minaiyan
- Department of Pharmacology, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
| |
Collapse
|
|
7
|
Abdel-Aziz H, Schneider M, Neuhuber W, Meguid Kassem A, Khailah S, Müller J, Gamal Eldeen H, Khairy A, T Khayyal M, Shcherbakova A, Efferth T, Ulrich-Merzenich G. GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis. Mol Med 2016; 21:1011-1024. [PMID: 26650186 DOI: 10.2119/molmed.2015.00098] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Accepted: 11/23/2015] [Indexed: 01/01/2023] Open
Abstract
Gastro-esophageal reflux disease (GERD) is one of the most common disorders in gastroenterology. Patients present with or without increased acid exposure indicating a nonuniform etiology. Thus, the common treatment with proton pump inhibitors (PPIs) fails to control symptoms in up to 40% of patients. To further elucidate the pathophysiology of the condition and explore new treatment targets, transcriptomics, proteomics and histological methods were applied to a surgically induced subchronic reflux esophagitis model in Wistar rats after treatment with either omeprazole (PPI) or STW5, a herbal preparation shown to ameliorate esophagitis without affecting refluxate pH. The normal human esophageal squamous cell line HET-1A and human endoscopic biopsies were used to confirm our findings to the G-protein-coupled receptor (GPR) 84 in human tissue. Both treatments reduced reflux-induced macroscopic and microscopic lesions of the esophagi as well as known proinflammatory cytokines. Proteomic and transcriptomic analyses identified CINC1-3, MIP-1/3α, MIG, RANTES and interleukin (IL)-1β as prominent mediators in GERD. Most regulated cyto-/chemokines are linked to the TREM-1 signaling pathway. The fatty acid receptor GPR84 was upregulated in esophagitis but significantly decreased in treated groups, a finding supported by Western blot and immunohistochemistry in both rat tissue and HET-1A cells. GPR84 was also found to be significantly upregulated in patients with grade B reflux esophagitis. The expression of GPR84 in esophageal tissue and its potential involvement in GERD are reported for the first time. IL-8 (CINC1-3) and the TREM-1 signaling pathway are proposed, besides GPR84, to play an important role in the pathogenesis of GERD.org.
Collapse
Affiliation(s)
- Heba Abdel-Aziz
- Department of Pharmacology, Institute of Pharmaceutical Chemistry, Westfalian Wilhelms University, Münster, Germany
| | - Mathias Schneider
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany
| | - Winfried Neuhuber
- Institute of Anatomy, University of Erlangen-Nürnberg, Erlangen, Germany
| | - Abdel Meguid Kassem
- Tropical Medicine Department and Gastrointestinal Endoscopy Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Saleem Khailah
- Tropical Medicine Department and Gastrointestinal Endoscopy Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Jürgen Müller
- Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany
| | - Hadeel Gamal Eldeen
- Tropical Medicine Department and Gastrointestinal Endoscopy Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Khairy
- Tropical Medicine Department and Gastrointestinal Endoscopy Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed T Khayyal
- Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Anastasiia Shcherbakova
- Medical Clinic III, University Clinic Centre, Rheinische Friedrich-Wilhelms University, Bonn, Germany
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany
| | - Gudrun Ulrich-Merzenich
- Medical Clinic III, University Clinic Centre, Rheinische Friedrich-Wilhelms University, Bonn, Germany
| |
Collapse
|
|
8
|
Hu XT, Ding C, Zhou N, Xu C. Quercetin protects gastric epithelial cell from oxidative damage in vitro and in vivo. Eur J Pharmacol 2015; 754:115-24. [DOI: 10.1016/j.ejphar.2015.02.007] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Revised: 02/03/2015] [Accepted: 02/10/2015] [Indexed: 12/22/2022]
|
|
9
|
Malek HA, Shalaby A. The preventive effect of β3 adrenoceptor stimulation against experimentally induced reflux esophagitis. ACTA ACUST UNITED AC 2015; 102:94-104. [PMID: 25804391 DOI: 10.1556/aphysiol.102.2015.1.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
UNLABELLED A β3 adrenoceptor agonist plays an important regulatory role in stimulation of thermogenesis and lipolysis and it appears to have anti-ulcer and spasmolytic effects. So the present aim was to examine the effect of BRL 37344 (a selective B3 adrenoceptor agonist) on reflux esophagitis. METHODS Forty-eight rats were divided into twelve sham-operated with BRL 37344 and/or omeprazole with or without indomethacin. RE was induced in rats, then gastric acid output, pH, plasma nitric oxide (NO), esophageal PGE2, malondialdehyde (MDA) and reduced glutathione (GSH) were measured and the esophageal injury was assessed by macroscopic damage score. RESULTS Pretreatment with BRL significantly increased plasma NO, GSH, decreased acid output, esophageal MDA and esophageal injury in comparison to pretreatment. In addition, there was a no significant increase in esophageal PGE2. CONCLUSION It can be concluded that BRL 37344 has an anti-oxidant protective effect in rats with RE.
Collapse
Affiliation(s)
- Hala Abdel Malek
- Mansoura University, Faculty of Medicine Clinical Pharmacology Department Mansoura Egypt
| | - A Shalaby
- Mansoura University, Faculty of Medicine Clinical Pharmacology Department Mansoura Egypt
| |
Collapse
|
|
10
|
Acute toxicity and gastroprotective role of M. pruriens in ethanol-induced gastric mucosal injuries in rats. BIOMED RESEARCH INTERNATIONAL 2013; 2013:974185. [PMID: 23781513 PMCID: PMC3678452 DOI: 10.1155/2013/974185] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2013] [Revised: 04/27/2013] [Accepted: 05/01/2013] [Indexed: 12/29/2022]
Abstract
The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC). The reference control was administered omeprazole orally (20 mg/kg). The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500 mg/kg) and the experimental groups (62.5, 125, 250, and 500 mg/kg). After 1 h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1 h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5 g/kg) and could enhance defensive mechanisms against hemorrhagic mucosal lesions.
Collapse
|
|
11
|
El-Nezhawy AOH, Biuomy AR, Hassan FS, Ismaiel AK, Omar HA. Design, synthesis and pharmacological evaluation of omeprazole-like agents with anti-inflammatory activity. Bioorg Med Chem 2013; 21:1661-70. [PMID: 23453216 DOI: 10.1016/j.bmc.2013.01.070] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2012] [Revised: 01/19/2013] [Accepted: 01/28/2013] [Indexed: 01/08/2023]
Abstract
A new series of novel benzimidazole derivatives containing substituted pyrid-2-yl moiety and polyhydroxy sugar conjugated to the N-benzimidazole moiety has been synthesized and evaluated as orally bioavailable anti-inflammatory agents with anti-ulcerogenic activity. The anti-inflammatory and anti-ulcerogenic activities of these compounds were compared to diclofenac and omeprazole, respectively. In carrageenan-induced paw oedema assay, 2-methyl-N-((3,4-dimethoxypyridin-2-yl)methyl)-1H-benzimidazol-5-amine (12d) and 1-(1,2,3,5-tetrahydroxy-α-D-mannofuranose)-5-(((3,4-dimethoxypyridin-2yl)methyl)amino)-2-methyl-1H-benzimidazole (15d) displayed dose-dependent anti-inflammatory activities by decreasing the inflammation by 62% and 72%, respectively which is comparable to that of diclofenac (73%). In contrast to diclofenac, the anti-inflammatory activity of these compounds was not only free from any side effects on the gastric mucosa but also showed significant anti-ulcerogenic activity in rat pyloric ligation and ethanol-induced gastric ulcer models similar to that of omeprazole. Together, these findings suggest that 12d and 15d are potent anti-inflammatory agents with concurrent anti-ulcerogenic activity and support its clinical promise as a component of therapeutic strategies for inflammation, for which the gastric side effects are always a major limitation.
Collapse
Affiliation(s)
- Ahmed O H El-Nezhawy
- Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Saudi Arabia.
| | | | | | | | | |
Collapse
|
|
12
|
El-Shinnawy NA, Abd-Elmageid SA, Alshailabi EMA. Evaluation of antiulcer activity of indole-3-carbinol and/or omeprazole on aspirin-induced gastric ulcer in rats. Toxicol Ind Health 2012; 30:357-75. [DOI: 10.1177/0748233712457448] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The present work is an attempt to elucidate the antiulcer activity of indole-3-carbinol (I3C), which is one of the anticarcinogenic phytochemicals found in the vegetables of Cruciferae family such as broccoli and cauliflower, alone or in combination with omeprazole (OMP), a proton pump inhibitor, to diminish the effects of induced acute gastric ulcer by aspirin (ASA) in male albino rats. A total of 48 adult male albino rats were used in the present study. Animals were divided into eight experimental groups (six animals each group). They were given different experimental inductions of ASA at a dose of 500 mg/kg/body weight, OMP at a dose of 20 mg/kg/body weight and I3C at a dose of 20 mg/kg/body weight either alone or in combination with each other orally for a duration of 7 days. Inner stomach features, ulcer index, pH activity, body weight, stomach weight, hematological investigations, serum total protein albumin and reduced glutathione activity were investigated in addition to the histological, histochemical and immunohistochemical stain of cyclooxygenase-2 to the stomach tissue of normal control, ulcerated and treated ulcerated rats. The results of this study revealed that oral administration of ASA to rats produced the expected characteristic mucosal lesions. OMP accelerated ulcer healing but the administration of I3C either alone or in combination with OMP to ASA-ulcerated rats produced a profound protection to the gastric mucosa from injury induced by ASA. Our results suggested that administration of antiulcer natural substances such as I3C in combination with the perused treatment such as OMP is a very important initiative in the development of new strategies in ulcer healing.
Collapse
Affiliation(s)
- Nashwa A El-Shinnawy
- Department of Zoology, Women’s College for Arts, Science and Education, Ain Shams University, Cairo, Egypt
| | - Samira A Abd-Elmageid
- Department of Zoology, Women’s College for Arts, Science and Education, Ain Shams University, Cairo, Egypt
| | | |
Collapse
|
|
13
|
Shivanna B, Chu C, Welty SE, Jiang W, Wang L, Couroucli XI, Moorthy B. Omeprazole attenuates hyperoxic injury in H441 cells via the aryl hydrocarbon receptor. Free Radic Biol Med 2011; 51:1910-7. [PMID: 21906671 PMCID: PMC3901644 DOI: 10.1016/j.freeradbiomed.2011.08.013] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2011] [Revised: 08/16/2011] [Accepted: 08/17/2011] [Indexed: 10/17/2022]
Abstract
Hyperoxia contributes to the development of bronchopulmonary dysplasia in premature infants. Earlier we observed that aryl hydrocarbon receptor (AhR)-deficient mice are more susceptible to hyperoxic lung injury than AhR-sufficient mice, and this phenomenon was associated with a lack of expression of cytochrome P450 1A enzymes. Omeprazole, a proton pump inhibitor used in humans with gastric acid-related disorders, activates AhR in hepatocytes in vitro. However, the effects of omeprazole on AhR activation in the lungs and its impact on hyperoxia-induced reactive oxygen species (ROS) generation and inflammation are unknown. In this study, we tested the hypothesis that omeprazole attenuates hyperoxia-induced cytotoxicity, ROS generation, and expression of monocyte chemoattractant protein-1 (MCP-1) in human lung-derived H441 cells via AhR activation. Experimental groups included cells transfected with AhR small interfering RNA (siRNA). Hyperoxia resulted in significant increases in cytotoxicity, ROS generation, and MCP-1 production, which were significantly attenuated with the functional activation of AhR by omeprazole. The protective effects of omeprazole on cytotoxicity, ROS production, and MCP-1 production were lost in H441 cells whose AhR gene was silenced by AhR siRNA. These findings support the hypothesis that omeprazole protects against hyperoxic injury in vitro via AhR activation that is associated with decreased ROS generation and expression of MCP-1.
Collapse
Affiliation(s)
- Binoy Shivanna
- Division of Neonatal–Perinatal Medicine, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
| | | | | | | | | | | | | |
Collapse
|
|
14
|
Shivanna B, Jiang W, Wang L, Couroucli XI, Moorthy B. Omeprazole attenuates hyperoxic lung injury in mice via aryl hydrocarbon receptor activation and is associated with increased expression of cytochrome P4501A enzymes. J Pharmacol Exp Ther 2011; 339:106-14. [PMID: 21768223 PMCID: PMC3186283 DOI: 10.1124/jpet.111.182980] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2011] [Accepted: 07/15/2011] [Indexed: 11/22/2022] Open
Abstract
Hyperoxia contributes to lung injury in experimental animals and bronchopulmonary dysplasia (BPD) in preterm infants. Cytochrome P4501A (CYP1A) enzymes, which are regulated by the aryl hydrocarbon receptor (AhR), have been shown to attenuate hyperoxic lung injury in rodents. Omeprazole, a proton pump inhibitor, used in humans to treat gastric acid-related disorders, induces hepatic CYP1A in vitro. However, the mechanism by which omeprazole induces CYP1A and its impact on CYP1A expression in vivo and hyperoxic lung injury are unknown. Therefore, we tested the hypothesis that omeprazole attenuates hyperoxic lung injury in adult wild-type (WT) C57BL/6J mice by an AhR-mediated induction of pulmonary and hepatic CYP1A enzymes. Accordingly, we determined the effects of omeprazole on pulmonary and hepatic CYP1A expression and hyperoxic lung injury in adult WT and AhR dysfunctional (AhRd) mice. We found that omeprazole attenuated lung injury in WT mice. Attenuation of lung injury by omeprazole paralleled enhanced pulmonary CYP1A1 and hepatic CYP1A2 expression in the omeprazole-treated mice. On the other hand, omeprazole failed to enhance pulmonary CYP1A1 and hepatic CYP1A2 expression and protect against hyperoxic lung injury in AhRd mice. In conclusion, our results suggest that omeprazole attenuates hyperoxic lung injury in mice by AhR-mediated mechanisms, and this phenomenon is associated with induction of CYP1A enzymes. These studies have important implications for the prevention and/or treatment of hyperoxia-induced disorders such as BPD in infants and acute respiratory distress syndrome in older children and adults.
Collapse
Affiliation(s)
- Binoy Shivanna
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA
| | | | | | | | | |
Collapse
|
|
15
|
Different Mechanisms in Formation and Prevention of Indomethacin-induced Gastric Ulcers. Inflammation 2010; 33:224-34. [DOI: 10.1007/s10753-009-9176-5] [Citation(s) in RCA: 84] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
|
|
16
|
The anti-secretory and anti-ulcer activities of esomeprazole in comparison with omeprazole in the stomach of rats and rabbits. Mol Cell Biochem 2007; 309:167-75. [PMID: 18044010 DOI: 10.1007/s11010-007-9657-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2007] [Accepted: 11/14/2007] [Indexed: 01/02/2023]
Abstract
Proton pump inhibitors (PPIs) are widely used to treat hyperacid secretion and stomach ulcers. The study investigated the anti-secretory and anti-ulcer effects of esomeprazole, the S-isomer of omeprazole on dimaprit, histamine and dibutyryl adenosine 3, 5 cyclic monophosphate (dbcAMP)-evoked gastric acid secretion, acidified ethanol (AE) and indomethacin (INDO)-induced haemorrhagic lesions and on prostaglandin E2 (PGE2) level in the rat in vivo and rabbit in vitro preparations. The effect of omeprazole was also investigated for comparison. Dimaprit-induced acid secretion was significantly (P < 0.05) inhibited by both PPIs in a dose-dependent manner. In the isolated rabbit gastric glands, both PPIs elicited marked reductions in histamine- and dbcAMP-evoked acid secretion with similar potency. The lesions induced by either AE or INDO were significantly (P < 0.05) reduced in the presence of either esomeprazole or omeprazole compared to control values. Increasing doses of esomeprazole before AE treatment resulted in a marked degree of cytoprotection and an elevation in the concentration of bound PGE2 in the stomach tissue homogenate. The results show that esomeprazole and omeprazole were equally effective against gastric haemorrhagic lesions induced by either AE or INDO and in inhibiting dimaprit-, dbcAMP- and histamine-induced gastric acid secretion in the rat and rabbit stomach both in vivo and in vitro. The gastro-protective effect of esomeprazole was found to be proportional to the bound PGE2 levels in the glandular area of the stomach.
Collapse
|
|
17
|
da Silveira ABM, Adad SJ, Correa-Oliveira R, Furness JB, D'Avila Reis D. Morphometric study of eosinophils, mast cells, macrophages and fibrosis in the colon of chronic chagasic patients with and without megacolon. Parasitology 2007; 134:789-96. [PMID: 17288632 DOI: 10.1017/s0031182007002296] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The mechanisms involved in the pathogenesis of chagasic megacolon are not completely characterized. Although autoimmunity may play a role in the pathogenesis of Chagas' disease, recent studies suggest a positive association of tissue parasitism, inflammation, and severity of lesions. The aim of this study was to evaluate the role of inflammatory cells and the occurrence of fibrosis in the colon of chagasic patients with and without megacolon. Samples from 26 patients were randomly selected and paraffin-embedded tissue blocks were sectioned and evaluated by histology and immunohistochemistry to analyse the occurrence and relation among eosinophils, mast cells, macrophages and fibrosis. Section analyses showed that the presence of eosinophils and mast cells in the analysed inflammatory cells has a direct correlation with fibrosis density in the chagasic megacolon. These data suggest that the megacolon's pathogenesis is based on a continuous process of cell damage. Our data propose that eosinophils, mast cells and macrophages may have a direct connection with the occurrence of fibrosis in the colon of chagasic patients. We believe that potential therapeutic agents against these cells could avoid the fibrosis process and contribute to prevent the development of chagasic megacolon.
Collapse
Affiliation(s)
- A B M da Silveira
- Department of Morphology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil.
| | | | | | | | | |
Collapse
|
|
18
|
Pozzoli C, Menozzi A, Grandi D, Solenghi E, Ossiprandi MC, Zullian C, Bertini S, Cavestro GM, Coruzzi G. Protective effects of proton pump inhibitors against indomethacin-induced lesions in the rat small intestine. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2007; 374:283-91. [PMID: 17151854 DOI: 10.1007/s00210-006-0121-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2006] [Accepted: 11/08/2006] [Indexed: 12/24/2022]
Abstract
Proton pump inhibitors (PPIs) have been shown to be effective in preventing gastric and duodenal ulcers in high-risk patients taking nonsteroidal anti-inflammatory drugs (NSAIDs); by contrast, scarce information is available concerning the effects of PPIs on intestinal damage induced by NSAIDs in humans or in experimental animals. We examined the effects of lansoprazole and omeprazole on the intestinal injury induced by indomethacin in the conscious rat. PPIs were administered by the intragastric route at 30, 60 and 90 micromol/kg, 12 h and 30 min before and 6 h after indomethacin treatment. The effects of omeprazole and lansoprazole were evaluated on: (1) macroscopic and histologic damage; (2) mucosal polymorphonuclear cell infiltration; (3) oxidative tissue damage and (4) bacterial translocation from lumen into the intestinal mucosa. Lansoprazole and omeprazole (at 90 micromol/kg) significantly decreased (P<0.01) the macroscopic and histologic damage induced by indomethacin in the rat small intestine. Furthermore, both drugs greatly reduced (P<0.01) the associated increases in myeloperoxidase levels and lipid peroxidation induced by indomethacin, whereas they only moderately affected (P<0.05) the translocation of enterobacteria from lumen into the intestinal mucosa. These data demonstrate that omeprazole and lansoprazole can protect the small intestine from the damage induced by indomethacin in the conscious rat. The intestinal protection, possibly related to antioxidant and anti-inflammatory properties of these drugs, may suggest new therapeutic uses of PPIs in intestinal inflammatory diseases.
Collapse
Affiliation(s)
- Cristina Pozzoli
- Department of Human Anatomy, Pharmacology and Forensic Medicine, University of Parma, Via Volturno 39, Parma, Italy
| | | | | | | | | | | | | | | | | |
Collapse
|
|
19
|
Melo JR, de Araújo GKM, da Luz MMP, da Conceição SA, Lisboa FA, Moraes-Santos T, Cunha-Melo JR. Effect of acid secretion blockade on acute gastric mucosal lesions induced by Tityus serrulatus scorpion toxin in anaesthetized rats. Toxicon 2006; 48:543-9. [PMID: 16926041 DOI: 10.1016/j.toxicon.2006.07.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2006] [Revised: 06/26/2006] [Accepted: 07/03/2006] [Indexed: 01/18/2023]
Abstract
Scorpion venom (TX) promotes gastric acid and pepsin secretion leading to acute gastric mucosal lesions (AGML), when injected in animals. The goal of the present study was to observe the effects of acid gastric secretion blockers over the incidence of TX-induced AGML in vivo. To verify this model, we used male albino rats, fasted 18-20 h (n=122) and anaesthetized with urethane (1.4 g/kg, i.p.). Their trachea and left femoral vein were both cannulated; the first to avoid airway obstructions during scorpion intoxication and the second for administration of saline, TX and acid blockers. Following the surgical procedure, the animals were divided in 10 groups of at least 10 animals each. Control groups were injected with NaCl 0.9% 1 ml/kg (n=10) or TX 375 microg/kg (n=32). Test groups (n=10, each) received atropine 5 mg/kg, cimetidine 10mg/kg, ranitidine 2.5mg/kg, ranitidine 5mg/kg, omeprazol 1 mg/kg, omeprazol 4 mg/kg, octreotide 80 and octreotide 100 microg/kg 10 min before the TX was injected. After 1h of intoxication, the stomach was resected for macroscopic study and the gastric secretion was collected for volume, pH and acid output assessment. We observed that all blockers were able to completely or partially prevent the TX-induced acid secretion as well as the AGML (p<0.05). Our data suggest the TX-induced AGML can be prevented by different class of acid blockers injected before the intoxication.
Collapse
Affiliation(s)
- Júnio Rios Melo
- Department of Surgery, School of Medicine, Universidade Federal de Minas Gerais (UFMG), Avenida Alfredo Balena, 190/4003, Bairro Santa Efigênia, CEP 30130-100, Belo Horizonte, MG, Brazil
| | | | | | | | | | | | | |
Collapse
|
|
20
|
Chattopadhyay I, Bandyopadhyay U, Biswas K, Maity P, Banerjee RK. Indomethacin inactivates gastric peroxidase to induce reactive-oxygen-mediated gastric mucosal injury and curcumin protects it by preventing peroxidase inactivation and scavenging reactive oxygen. Free Radic Biol Med 2006; 40:1397-408. [PMID: 16631530 DOI: 10.1016/j.freeradbiomed.2005.12.016] [Citation(s) in RCA: 96] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2005] [Revised: 11/28/2005] [Accepted: 12/11/2005] [Indexed: 12/30/2022]
Abstract
We have investigated the mechanism of indomethacin-induced gastric ulcer caused by reactive oxygen species (ROS) and the gastroprotective effect of curcumin thereon. Curcumin dose-dependently blocks indomethacin-induced gastric lesions, showing 82% protection at 25 mg/kg. Indomethacin-induced oxidative damage by ROS as shown by increased lipid peroxidation and thiol depletion is almost completely blocked by curcumin. Indomethacin causes nearly fivefold increase in hydroxyl radical (()OH) and significant inactivation of gastric mucosal peroxidase to elevate endogenous H(2)O(2) and H(2)O(2)-derived ()OH, which is prevented by curcumin. In vitro studies indicate that indomethacin inactivates peroxidase irreversibly only in presence of H(2)O(2) by acting as a suicidal substrate. 5,5-Dimethyl-pyrroline-N-oxide (DMPO) protects the peroxidase, indicating involvement of indomethacin radical in the inactivation. Indomethacin radical was also detected in the peroxidase-indomethacin-H(2)O(2) system as DMPO adduct (a(N) = 15 G, a(beta)(H) = 16 G) by electron spin resonance spectroscopy. Curcumin protects the peroxidase in a concentration-dependent manner and consumes H(2)O(2) for its oxidation as a suitable substrate of the peroxidase, thereby blocking indomethacin oxidation. Curcumin can also scavenge ()OH in vitro. We suggest that curcumin protects gastric damage by efficient removal of H(2)O(2) and H(2)O(2) -derived ()OH by preventing peroxidase inactivation by indomethacin.
Collapse
|
|
21
|
Kamiya Y, Ohta Y, Imai Y, Arisawa T, Nakano H. A critical role of gastric mucosal ascorbic acid in the progression of acute gastric mucosal lesions induced by compound 48/80 in rats. World J Gastroenterol 2005; 11:1324-32. [PMID: 15761970 PMCID: PMC4250679 DOI: 10.3748/wjg.v11.i9.1324] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the role of gastric mucosal ascorbic acid (AA) in the progression of acute gastric mucosal lesions induced by compound 48/80 (C48/80), a mast cell degranulator, in rats.
METHODS: C48/80 (0.75 mg/kg) was intraperitoneally injected to fasted Wistar rats. Oral administration of AA (10, 50 or 100 mg/kg) was performed 0.5 h after C48/80 treatment. Determinations for gastric mucosal lesion severity and blood flow, and assays for gastric mucosal total AA, reduced AA, oxidized AA, vitamin E, thiobarbituric acid reactive substances (TBARS), adherent mucus, nitrite/nitrate (NOx), non-protein SH (NPSH), and myeloperoxidase (MPO), and serum total AA, reduced AA, oxidized AA, and NOx were conducted 0.5 and 3 h after C48/80 treatment.
RESULTS: Gastric mucosal lesions occurred 0.5 h after C48/80 treatment and progressed at 3 h. Gastric mucosal blood flow decreased 0.5 h after C48/80 treatment but the decrease was recovered at 3 h. Gastric mucosal total AA, reduced AA, vitamin E, and adherent mucus concentrations decreased 3 h after C48/80 treatment. Gastric mucosal oxidized AA concentration remained unchanged after C48/80 treatment. Gastric mucosal NPSH concentration decreased 0.5 h after C48/80 treatment, but the decrease was recovered at 3 h. Gastric mucosal TBARS concentration and MPO activity increased 0.5 h after C48/80 treatment and further increased at 3 h. Serum total AA and reduced AA concentrations increased 0.5 h after C48/80 treatment and further increased at 3 h, while serum oxidized AA concentration increased at 0.5 h. Serum and gastric mucosal NOx concentrations increased 3 h after C48/80 treatment. AA administration to C48/80-treated rats at 0.5 h after the treatment prevented the gastric mucosal lesion progression and the changes in gastric mucosal total AA, reduced AA, vitamin E, adherent mucus, NOx, and TBARS concentrations and MPO activity and serum NOx concentration found at 3 h after the treatment dose-dependently. The AA administration to C48/80-treated rats caused further increases in serum total AA and reduced AA concentrations at 3 h after the treatment dose-dependently.
CONCLUSION: Gastric mucosal AA plays a critical role in the progression of C48/80-induced acute gastric mucosal lesions in rats.
Collapse
Affiliation(s)
- Yoshio Kamiya
- Department of Internal Medicine, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan
| | | | | | | | | |
Collapse
|
|
22
|
Bandyopadhyay U, Biswas K, Sengupta A, Moitra P, Dutta P, Sarkar D, Debnath P, Ganguly CK, Banerjee RK. Clinical studies on the effect of Neem (Azadirachta indica) bark extract on gastric secretion and gastroduodenal ulcer. Life Sci 2004; 75:2867-78. [PMID: 15454339 DOI: 10.1016/j.lfs.2004.04.050] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2003] [Accepted: 04/07/2004] [Indexed: 01/27/2023]
Abstract
We have shown earlier that Neem (Azadirachta indica) bark aqueous extract has potent antisecretory and antiulcer effects in animal models and has no significant adverse effect (Bandyopadhyay et al., Life Sciences, 71, 2845-2865, 2002). The objective of the present study was to investigate whether Neem bark extract had similar antisecretory and antiulcer effects in human subjects. For this purpose, a group of patients suffering from acid-related problems and gastroduodenal ulcers were orally treated with the aqueous extract of Neem bark. The lyophilised powder of the extract when administered for 10 days at the dose of 30 mg twice daily caused a significant (p < 0.002) decrease (77%) in gastric acid secretion. The volume of gastric secretion and its pepsin activity were also inhibited by 63% and 50%, respectively. Some important blood parameters for organ toxicity such as sugar, urea, creatinine, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, albumin, globulin, hemoglobin levels and erythrocyte sedimentation rate remained close to the control values. The bark extract when taken at the dose of 30-60 mg twice daily for 10 weeks almost completely healed the duodenal ulcers monitored by barium meal X-ray or by endoscopy. One case of esophageal ulcer (gastroesophageal reflux disease) and one case of gastric ulcer also healed completely when treated at the dose of 30 mg twice daily for 6 weeks. The levels of various blood parameters for organ toxicity after Neem treatment at the doses mentioned above remained more or less close to the normal values suggesting no significant adverse effects. Neem bark extract thus has therapeutic potential for controlling gastric hypersecretion and gastroesophageal and gastroduodenal ulcers.
Collapse
Affiliation(s)
- Uday Bandyopadhyay
- Department of Physiology, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata, 700032, India.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
23
|
Gao ZJ, Luo HS, Cao JW, Yu BP, Song LL. Effect of mast cell in pathogenesis of gastric eosinophilic granuloma. Shijie Huaren Xiaohua Zazhi 2003; 11:1203-1206. [DOI: 10.11569/wcjd.v11.i8.1203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the function of mast cells in the pathogenesis of gastric eosinophilic granuloma.
METHODS Paraffin embedded tissue sections from 23 gastric eosinophilic granuloma patients and 15 gastric ulcer patients were stained with anti-human mast cell tryptase to count the mast cells and degranulated mast cells. Anti-human CD34 antibody was used to detect the mocrovessel density with immunohistochemical technique. Mast cell degranulation was also studied by electron microscope.
RESULTS The quantity of mast cells in gastric eosinophilic granuloma was similar to that in gastric ulcer(9.1±3.0 vs 8.9±3.0, P>0.05). The quantity and ratio of degranulated mast cells were significantly greater in gastric eosinophilic granuloma patients than in gastric ulcer control subjects(7.3±2.4 vs 4.3±1.4, 80.3±15.7% vs 48.4±15.7%, P<0.01). Microvessel density was higher in the patients of high mast cell count than in patients of low mast cell count (57.3±10.7 vs 32.4±7.2, P<0.01). There was a positive relevance between the amount of mast cells and eosinophils (r = 0.931, P<0.01).
CONCLUSION Mast cells are important cells in the pathogenesis of gastric eosinophilic granuloma.
Collapse
Affiliation(s)
- Zhen-Jun Gao
- Division of Gastroenterology, People's Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - He-Sheng Luo
- Division of Gastroenterology, People's Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Ji-Wang Cao
- Division of Gastroenterology, People's Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Bao-Ping Yu
- Division of Gastroenterology, People's Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Liu-Lai Song
- Division of Gastroenterology, People's Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| |
Collapse
|
|
24
|
Biswas K, Bandyopadhyay U, Chattopadhyay I, Varadaraj A, Ali E, Banerjee RK. A novel antioxidant and antiapoptotic role of omeprazole to block gastric ulcer through scavenging of hydroxyl radical. J Biol Chem 2003; 278:10993-1001. [PMID: 12529378 DOI: 10.1074/jbc.m210328200] [Citation(s) in RCA: 210] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The mechanism of the antiulcer effect of omeprazole was studied placing emphasis on its role to block oxidative damage and apoptosis during ulceration. Dose-response studies on gastroprotection in stress and indomethacin-induced ulcer and inhibition of pylorus ligation-induced acid secretion indicate that omeprazole significantly blocks gastric lesions at lower dose (2.5 mg/kg) without inhibiting acid secretion, suggesting an independent mechanism for its antiulcer effect. Time course studies on gastroprotection and acid reduction also indicate that omeprazole almost completely blocks lesions at 1 h when acid inhibition is partial. The severity of lesions correlates well with the increased level of endogenous hydroxyl radical (*OH), which when scavenged by dimethyl sulfoxide causes around 90% reduction of the lesions, indicating that *OH plays a major role in gastric damage. Omeprazole blocks stress-induced increased generation of *OH and associated lipid peroxidation and protein oxidation, indicating that its antioxidant role plays a major part in preventing oxidative damage. Omeprazole also prevents stress-induced DNA fragmentation, suggesting its antiapoptotic role to block cell death during ulceration. The oxidative damage of DNA by *OH generated in vitro is also protected by omeprazole or its analogue, lansoprazole. Lansoprazole when incubated in a *OH-generating system scavenges *OH to produce four oxidation products of which the major one in mass spectroscopy shows a molecular ion peak at m/z 385, which is 16 mass units higher than that of lansoprazole (m/z 369). The product shows no additional aromatic proton signal for aromatic hydroxylation in (1)H NMR. The product absorbing at 278 nm shows no alkaline shift for phenols, thereby excluding the formation of hydroxylansoprazole. The product is assigned to lansoprazole sulfone formed by the addition of one oxygen atom at the sulfur center following attack by the *OH. Thus, omeprazole plays a significant role in gastroprotection by acting as a potent antioxidant and antiapoptotic molecule.
Collapse
Affiliation(s)
- Kaushik Biswas
- Department of Physiology, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700 032, India
| | | | | | | | | | | |
Collapse
|