|
1
|
Azmatullah S, Khan AU, Qazi NG, Nadeem H, Irshad N. Pharmacological evaluation of newly synthesized organotin IV complex for antiulcer potential. BMC Pharmacol Toxicol 2022; 23:58. [PMID: 35906691 PMCID: PMC9335977 DOI: 10.1186/s40360-022-00596-0] [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: 02/21/2022] [Accepted: 07/12/2022] [Indexed: 11/29/2022] Open
Abstract
The present study aims to investigate the newly synthesized organotin (IV) complex (2E, 2′E) dibutylstannanediyl bis (4-(4-nitrophenyl) amino)-4-oxobut-2-enoate (DTN) for its anti-ulcer potential. Characterization performed by carbon nuclear magnetic resonance spectroscopy proved that all values are in the expected ranges of the new compound. Gastroprotective activity of DTN was evaluated through in-silico, anti-H. pylori, in-vitro, in-vivo, and ex-vivo proteomic analysis. In-silico analysis shows that DTN possess stable binding with protein targets involved in gastric ulcer pathophysiology. DTN exhibited an inhibitory effect against 2,2-diphenyl-1-picrylhydrazyl, H. pylori and hydrogen potassium ATPase (H+/K+-ATPase). The antiulcer activity was performed using an ethanol-induced gastric ulcer model in rats. Anti-oxidant profile of DTN showed a significant increase in glutathione-S-transferase, glutathione and catalase levels whereas lipid peroxidation levels were reduced. Histopathological findings confirmed that DTN protected the gastric mucosa of rats. Inflammatory markers tumor necrosis factor-alpha, nuclear factor kappa B, cyclooxygenase-2, interleukin 6 and interleukin-1β were reduced and prostaglandin-E2 restored expression of these cytokines in DTN pretreated animals when analyzed by using immunohistochemistry, enzyme-linked immunosorbent assay and western blot techniques. In real-time polymerase chain reaction technique, the expression of H+/K+-ATPase was downregulated in DTN pretreated group. DTN did not cause any mortality up to 400 mg/Kg. This study indicates that the newly synthesized compound DTN, possess stable binding against selected targets. DTN exhibits a gastro-protective effect, mediated via anti-H. pylori, H+/K+-ATPase inhibition, anti-oxidant and anti-inflammatory pathways, exploring its therapeutic potential in gastric ulcer management.
Collapse
Affiliation(s)
- Syed Azmatullah
- Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan
| | - Arif-Ullah Khan
- Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
| | - Neelam Gul Qazi
- Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan
| | - Humaira Nadeem
- Department of Pharmaceutical Chemistry, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan
| | - Nadeem Irshad
- Department of Pharmacy, Quaid i Azam University, Islamabad, Pakistan
| |
Collapse
|
|
2
|
He H, Li X, Yu H, Zhu S, He Y, Komatsu K, Guo D, Li X, Wang J, Luo H, Xu D, Zou K. Gastroprotective effect of araloside A on ethanol- and aspirin-induced gastric ulcer in mice: involvement of H +/K +-ATPase and mitochondrial-mediated signaling pathway. J Nat Med 2018; 73:339-352. [PMID: 30523551 DOI: 10.1007/s11418-018-1256-0] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Accepted: 10/12/2018] [Indexed: 12/11/2022]
Abstract
The aim of this study was to elucidate the gastroprotective activity and possible mechanism of involvement of araloside A (ARA) against ethanol- and aspirin-induced gastric ulcer in mice. The experimental mice were randomly divided into control, model, omeprazole (20 mg/kg, orally) and ARA (10, 20 and 40 mg/kg, orally). Gastric ulcer in mice was induced by intragastric administration of 80% ethanol (10 mL/kg) containing 15 mg/mL aspirin 4 h after drug administration on day 7. The results indicated that ARA could significantly raise gastric juice volume and acidity; ameliorate gastric mucosal blood flow, gastric binding mucus volume, ulcer index and ulcer inhibition rate; suppress H+/K+-ATPase activity, which was confirmed by computer-aided docking simulations; inhibit the release of mitochondrial cytochrome c into the cytoplasm; inhibit caspase-9 and caspase-3 activities and down-regulate mRNA expression levels; down-regulate the mRNA and protein expressions of apoptosis protease-activating factor-1 and protein expression of cleaved poly(ADP ribose) polymerase-1; and up-regulate Bcl-2 mRNA and protein expressions and down-regulate Bax mRNA and protein expressions, thus elevating the Bcl-2/Bax ratio in a dose-dependent manner. Histopathological observations further provided supportive evidence for the aforementioned results. The results demonstrated that ARA exerted beneficial gastroprotective effects on alcohol- and aspirin-induced gastric ulcer in mice, which was related to suppressing H+/K+-ATPase activity as well as pro-apoptotic protein expression, and promoting anti-apoptotic protein expression, thus alleviating gastric mucosal injury and cell death.
Collapse
Affiliation(s)
- Haibo He
- Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, 8 University Avenue, Yichang, 443002, China
| | - Xiaomei Li
- Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, 8 University Avenue, Yichang, 443002, China
| | - Haili Yu
- Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, 8 University Avenue, Yichang, 443002, China
| | - Shu Zhu
- Division of Pharmacognosy, Department of Medicinal Resources, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan
| | - Yumin He
- Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, 8 University Avenue, Yichang, 443002, China
| | - Katsuko Komatsu
- Division of Pharmacognosy, Department of Medicinal Resources, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan
| | - Dongyan Guo
- Shaanxi Key Laboratory of Traditional Chinese Medicine Foundation and New Drug Research, Shaanxi University of Chinese Medicine, Shiji Road, Xianyang, 712046, China.
| | - Xiaoqin Li
- Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, 8 University Avenue, Yichang, 443002, China
| | - Junzhi Wang
- Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, 8 University Avenue, Yichang, 443002, China.
| | - Huajun Luo
- Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, 8 University Avenue, Yichang, 443002, China
| | - Daoxiang Xu
- Seventh People's Hospital of Wenzhou, 552 Shanxi East Road, Wenzhou, 325005, China
| | - Kun Zou
- Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, 8 University Avenue, Yichang, 443002, China
| |
Collapse
|
|
3
|
Harvey R. Another 20th century epidemic. QJM 2012; 105:1034-5. [PMID: 22836194 DOI: 10.1093/qjmed/hcs131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
|
|
4
|
Kokkola A, Louhimo J, Puolakkainen P, Alfthan H, Haglund C, Rautelin H. Helicobacter pylori infection and low serum pepsinogen I level as risk factors for gastric carcinoma. World J Gastroenterol 2005; 11:1032-6. [PMID: 15742409 PMCID: PMC4250766 DOI: 10.3748/wjg.v11.i7.1032] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [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 whether examination of CagA antibodies could increase the odds ratio for gastric cancer in a case-control study, and how often other serum markers of gastric cancer risk could be found in Helicobacter pylori -negative patients.
METHODS: H pylori CagA and parietal cell antibodies (PCAs), and serum pepsinogen I (SPGI) levels were compared between patients with gastric cancer and controls who received endoscopic examination due to reasons other than gastrointestinal malignancy.
RESULTS: The odds ratio (OR) for gastric cancer was 2.9 (95% CI 1.4-5.8) in H pylori+ patients, and 2.4 (95% CI 1.2-4.9) in CagA+ patients. When results of H pylori and CagA antibodies were combined, OR increased to 5.0 (95% CI 2.5-10.0). Furthermore, if cardia cancer patients were excluded, the OR increased to 6.8 (95% CI 3.1-14.8). Among patients with a low SPGI level, the OR was 12.0 (95% CI 4.1-35.3). However, the risk was significant only in the older age group. The number of patients with low SPGI was significantly higher in H pylori-/CagA+ patients as compared to other cancer patients.
CONCLUSION: Examination of both H pylori and CagA antibodies increases the OR for gastric cancer in our case-control study. CagA antibodies are important in detecting previous H pylori infection in advanced atrophic gastritis or cancer when spontaneous decline of H pylori antibodies occurs. SPGI may be helpful in screening elderly gastric cancer patients.
Collapse
Affiliation(s)
- Arto Kokkola
- Department of Surgery, Meilahti Hospital, PO Box 340 (Haartmaninkatu 4), FIN-00029 HUS, Finland.
| | | | | | | | | | | |
Collapse
|
|
5
|
Dominici P, Bellentani S, Di Biase AR, Saccoccio G, Le Rose A, Masutti F, Viola L, Balli F, Tiribelli C, Grilli R, Fusillo M, Grossi E. Familial clustering of Helicobacter pylori infection: population based study. BMJ (CLINICAL RESEARCH ED.) 1999; 319:537-540. [PMID: 10463891 PMCID: PMC28203 DOI: 10.1136/bmj.319.7209.537] [Citation(s) in RCA: 69] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 04/06/1999] [Indexed: 02/05/2023]
Abstract
OBJECTIVES To assess the rate of intrafamilial transmission of Helicobacter pylori infection in the general population and the role of a family's social background. DESIGN Population survey. SETTING Campogalliano, a town in northern Italy with about 5000 residents. PARTICIPANTS 3289 residents, accounting for 416 families. MAIN OUTCOME MEASURES Prevalence of H pylori infection assessed by presence of IgG antibodies to H pylori. RESULTS The overall prevalence of H pylori infection was 58%. Children belonging to families with both parents infected had a significantly higher prevalence of H pylori infection (44%) than children from families with only one (30%) or no parents (21%) infected (P<0.001). Multivariate analyses confirmed that children with both parents positive had double the risk of being infected by H pylori than those from families in which both parents were negative. Family social status was independently related to infection in children, with those from blue collar or farming families showing an increased risk of infection compared with children of white collars workers (odds ratio 2.02, 95% confidence interval 1.16 to 3.49). CONCLUSIONS H pylori infection clusters within families belonging to the same population. Social status may also be a risk factor. This suggests either a person to person transmission or a common source of exposure for H pylori infection.
Collapse
Affiliation(s)
- P Dominici
- Medical Department, Bracco SpA, 20134 Milano, Italy
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
6
|
Lee J, O'Morain C. Who should be treated for Helicobacter pylori infection? A review of consensus conferences and guidelines. Gastroenterology 1997; 113:S99-S106. [PMID: 9394769 DOI: 10.1016/s0016-5085(97)80021-2] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The publication of the National Institutes of Health Consensus Development Conference guidelines on management of Helicobacter pylori infection in 1994 set a precedence. At present, at least eight European countries have produced national guidelines, and, more recently, the European Helicobacter pylori Study Group also outlined guidelines based on the strength of available evidence. It is generally agreed that H. pylori should be eradicated in peptic ulcer disease. In nonsteroidal anti-inflammatory drug (NSAID)-related ulcers, most countries that considered the issue suggested discontinuing NSAIDs when possible and eradicating H. pylori. The prophylactic eradication of H. pylori was not recommended. A number of panels felt that there was not enough evidence available to recommend eradication of H. pylori in functional dyspepsia, whereas other groups felt that nonulcer dyspepsia, particularly after investigation and with severe or recurrent symptoms, was an indication for eradication therapy. Other conditions (i.e., gastroesophageal reflux disease [GERD] and mucosa-associated lymphoid tissue [MALT] lymphoma) have emerged in this short time as possible indications for H. pylori eradication. There is no evidence that H. pylori infection has a role in the pathogenesis of GERD, but there is evidence suggesting that patients with H. pylori infection who require long-term acid suppression may be at risk of developing atrophic gastritis. The European Helicobacter pylori Study Group has suggested that eradication therapy should be offered to infected family members of patients with gastric cancer. It also recommended that eradication therapy was "strongly recommended" on the basis of "supportive" evidence in gastritis with severe abnormalities and after early resection of early gastric cancer. An "uncertain" recommendation with "equivocal" evidence was given for asymptomatic subjects, extra-alimentary tract disease, the prevention of gastric cancer in the absence of risk factors, and in pediatric patients with recurrent abdominal pain. Despite considerable advances, further research studies are needed to provide definite direction for the treatment of many conditions.
Collapse
Affiliation(s)
- J Lee
- Department of Gastroenterology, Meath/Adelaide Hospitals, Trinity College, Dublin, Ireland
| | | |
Collapse
|
|
7
|
O'Connor HJ, Kanduru C, Bhutta AS, Meehan JM, Feeley KM, Cunnane K. Effect of Helicobacter pylori eradication on peptic ulcer healing. Postgrad Med J 1995; 71:90-3. [PMID: 7724441 PMCID: PMC2397943 DOI: 10.1136/pgmj.71.832.90] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
In a prospective study designed to assess the effect of Helicobacter pylori eradication on peptic ulcer healing, 85 consecutive patients with H. pylori-positive peptic ulcer disease were treated with a triple therapy regimen consisting of colloidal bismuth subcitrate 120 mg four times daily for 28 days, with metronidazole 400 mg three times daily and tetracycline 500 mg three times daily for the first seven days of treatment. H. pylori status was assessed by CLO test and histology at least four weeks after completing therapy. Of 75 patients (88%) H. pylori-negative after therapy, 69 (92%) had healed ulcers compared with only five of 10 patients (50%) who remained H. pylori-positive (p = 0.003). Cigarette smoking had no significant effect on ulcer healing. Our results suggest that H. pylori eradication may accelerate ulcer healing and provide further evidence that an effective helicobactericidal regimen is the treatment of choice in H. pylori-positive peptic ulcer.
Collapse
Affiliation(s)
- H J O'Connor
- Department of Medicine, General Hospital, Tullamore, Co Offaly, Eire
| | | | | | | | | | | |
Collapse
|
|
8
|
Abstract
Non-immunological defence mechanisms represent an important line of intestinal defence in addition to humoral and cellular immunity. This review summarises the evidence for the role of the non-immunological defence system. Protective factors that have been amply documented are gastric juice, intestinal motility, and intestinal flora. Components of pancreatic juice, lysozyme, and epithelial cell turnover may also be involved. Special attention is given to gastric acid, infection with Helicobacter pylori, and hypochlorhydria and their association with infectious diarrhoea. Epidemic hypochlorhydria is discussed since this increases sensitivity to intestinal infections in third world countries.
Collapse
Affiliation(s)
- S A Sarker
- Medical Department, Kantonsspital Liestal, University of Basel, Switzerland
| | | |
Collapse
|
|
9
|
Patchett S, Beattie S, Keane C, O'Morain C. Short report: short-term triple therapy for H. pylori-associated duodenal ulcer disease. Aliment Pharmacol Ther 1992; 6:113-7. [PMID: 1543813 DOI: 10.1111/j.1365-2036.1992.tb00551.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Thirty consecutive patients with endoscopically proven duodenal ulceration who had Helicobacter pylori infection on culture and histology, were treated with tripotassium dicitrato bismuthate (1 tablet q.d.s., 400 mg metronidazole t.d.s. and 500 mg tetracycline t.d.s. for one week, followed by the bismuth salt for a further 3 weeks. All patients were endoscoped at entry and 4 weeks after cessation of treatment, to check for ulcer healing and H. pylori eradication. Two antral biopsies were taken at each endoscopy for histological and microbiological evidence of H. pylori infection. Complete healing of duodenal ulcers was observed in 27/30 patients (90%). Gastritis improved or completely resolved in 26 patients. Eradication of H. pylori was achieved in 27 patients. Of the three patients who failed to heal, two were H. pylori-positive at follow-up and one was H. pylori-negative.
Collapse
Affiliation(s)
- S Patchett
- Department of Gastroenterology, Meath/Adelaide Hospitals, Trinity College, Dublin, Eire
| | | | | | | |
Collapse
|
|
10
|
|
|
11
|
Abstract
The clinical manifestations of Helicobacter pylori (formerly Campylobacter pylori) infection in children overlap with those encountered in adults but there are some important differences. The aim of this review is to describe the range of manifestations of this infection in children, together with means of diagnosis and treatment.
Collapse
Affiliation(s)
- P B Sullivan
- Department of Child Health, Westminster Children's Hospital, London, UK
| | | |
Collapse
|
|
12
|
Affiliation(s)
- M F Dixon
- Department of Pathology, University of Leeds, UK
| |
Collapse
|
|
13
|
Dixon MF. Progress in the pathology of gastritis and duodenitis. CURRENT TOPICS IN PATHOLOGY. ERGEBNISSE DER PATHOLOGIE 1990; 81:1-40. [PMID: 2407435 DOI: 10.1007/978-3-642-74662-8_1] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
|
|
14
|
Mertens JC, Dekker W, Ligtvoet EE, Blok P. Treatment failure of norfloxacin against Campylobacter pylori and chronic gastritis in patients with nonulcerative dyspepsia. Antimicrob Agents Chemother 1989; 33:256-7. [PMID: 2719469 PMCID: PMC171471 DOI: 10.1128/aac.33.2.256] [Citation(s) in RCA: 27] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Several reports have been published to show the in vitro susceptibility of Campylobacter pylori to different classes of antibiotics, including fluoroquinolones. The purpose of this study was to describe the clinical effect of norfloxacin on eradication of C. pylori in patients with gastritis. Endoscopy was performed in 38 patients with symptoms of nonulcerative dyspepsia. Of these, 20 patients had a C. pylori-positive culture. From this group, 17 patients were treated with norfloxacin for 1 month. After therapy, 15 patients still had positive cultures, and in 9 cases the strain was resistant to norfloxacin. These data, which confirm previous studies, support the concept that the in vitro activity of norfloxacin against C. pylori cannot be transposed to an in vivo effect.
Collapse
Affiliation(s)
- J C Mertens
- Department of Internal Medicine, St. Elisabeth's of Groote Gasthuis, Haarlem, The Netherlands
| | | | | | | |
Collapse
|
|
15
|
Wyatt JI. The role of Campylobacter pylori in the pathogenesis of peptic ulcer disease. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. SUPPLEMENT 1989; 157:7-11; discussion 21-2. [PMID: 2665051 DOI: 10.3109/00365528909091044] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Most patients with peptic ulceration have chronic gastritis, which typically involves predominantly the antrum. The association between Campylobacter pylori-associated gastritis and peptic ulceration has recently been repeatedly demonstrated. Evidence is accumulating that the bacterium plays a causal role in type-B chronic gastritis. C. pylori also colonizes the duodenum when gastric metaplasia is present. It is likely that the inflamed mucosa is more susceptible to ulcerogenic influences affecting either the stomach or duodenum.
Collapse
Affiliation(s)
- J I Wyatt
- Dept. of Histopathology, St. James's University Hospital, Leeds, U.K
| |
Collapse
|
|
16
|
Wormsley KG. Campylobacter pylori and ulcer disease--a causal connection? SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. SUPPLEMENT 1989; 160:53-8. [PMID: 2683023 DOI: 10.3109/00365528909091736] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
A strong positive correlation has been demonstrated between the (antral mucosal) presence of Campylobacter pylori and active duodenal and gastric ulceration. Moreover, both duodenal and gastric ulcers heal, and remain in remission, as a consequence of therapeutic measures which eradicate C. pylori. However, the Henle-Koch postulates have not been fulfilled, because C. pylori has not been shown to produce ulcers. As for the claim that ulcer disease represents an infection with C. pylori because therapeutic eradication heals ulcers, it has been shown that antibiotics and metronidazole, as well as bismuth subcitrate, exert antiulcer actions by mechanisms which do not involve their antibacterial effects. The association between C. pylori and ulcer disease, which was noted half a century ago, remains unexplained now as it did then.
Collapse
Affiliation(s)
- K G Wormsley
- Ninewells Hospital and Medical School, Dundee, Scotland
| |
Collapse
|