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1
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Kawashima R, Tsubokawa D, Iijima K, Ichikawa T. Extraction and Fractionation of Human Gastric Mucins from Gastric Juice. Methods Mol Biol 2024; 2763:61-69. [PMID: 38347400 DOI: 10.1007/978-1-0716-3670-1_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/15/2024]
Abstract
Mucin, a major component of the mucus, is considered to be one of the principal factors in the physiological defense mechanism of the gastrointestinal mucosa. Measuring the mucin content of human gastric mucus is a useful tool for the assessment of Helicobacter pylori (H. pylori) eradication or the involvement of mucus secretion in various gastroduodenal diseases. Here, we describe a methodology for the isolation of the mucin fraction from human gastric juice and the quantification of mucin.
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Affiliation(s)
- Rei Kawashima
- Department of Biochemistry, Kitasato University School of Allied Health Science, Sagamihara, Japan
| | - Daigo Tsubokawa
- Department of Biochemistry, Kitasato University School of Medicine, Sagamihara, Japan
| | - Katsunori Iijima
- Department of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan
| | - Takafumi Ichikawa
- Department of Biochemistry, Kitasato University School of Allied Health Science, Sagamihara, Japan.
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2
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Peripheral administration of Neuropeptide-W protects against stress-induced gastric injury in rats. Life Sci 2022; 310:121087. [DOI: 10.1016/j.lfs.2022.121087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 10/11/2022] [Accepted: 10/12/2022] [Indexed: 11/06/2022]
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Sawaya RD, Wakil C, Shayya S, Al Hariri M, Dakessian A, Wazir A, Makki M, Jamali S, Tamim H. Pediatric emergency department utilisation during Ramadan: a retrospective cross-sectional study. Arch Dis Child 2021; 106:272-275. [PMID: 32978143 DOI: 10.1136/archdischild-2020-319173] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Revised: 08/04/2020] [Accepted: 08/07/2020] [Indexed: 11/03/2022]
Abstract
OBJECTIVE To investigate the impact of Ramadan on patient characteristics, diagnoses and metrics in the paediatric emergency department (PED). DESIGN Retrospective cross-sectional study. SETTING PED of a tertiary care centre in Lebanon. PATIENTS All paediatric patients. EXPOSURE Ramadan (June 2016 and 2017) versus the months before and after Ramadan (non-Ramadan). MAIN OUTCOME MEASURES Patient and illness characteristics and PED metrics including peak patient load; presentation timings; length of stay; and times to order tests, receive samples and report results. RESULTS We included 5711 patients with mean age of 6.1±5.3 years and 55.4% males. The number of daily visits was 28.3±6.5 during Ramadan versus 31.5±7.3 during non-Ramadan (p=0.004). The peak time of visits ranged from 18:00 to 22:00 during non-Ramadan versus from 22:00 to 02:00 during Ramadan. During Ramadan, there were significantly more gastrointestinal (GI) and trauma-related complaints (39.0% vs 35.4%, p=0.01 and 2.9% vs 1.8%, p=0.005). The Ramadan group had faster work efficiency measures such as times to order tests (21.1±21.3 vs 24.3±28.1 min, p<0.0001) and to collect samples (50.7±44.5 vs 54.8±42.6 min, p=0.03). CONCLUSIONS Ramadan changes presentation patterns, with fewer daily visits and a later peak time of visits. Ramadan also affects illness presentation patterns with more GI and trauma cases. Fasting times during Ramadan did not affect staff work efficiency. These findings could help EDs structure their staffing to optimise resource allocation during Ramadan.
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Affiliation(s)
- Rasha D Sawaya
- Department of Emergency Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Cynthia Wakil
- Department of Emergency Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Sami Shayya
- Department of Emergency Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Moustafa Al Hariri
- Department of Emergency Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Alik Dakessian
- Department of Emergency Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Adonis Wazir
- Department of Emergency Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Maha Makki
- Clinical Research Institute, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Sarah Jamali
- Department of Emergency Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Hani Tamim
- Clinical Research Institute, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon .,Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
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Valcheva-Kuzmanova S, Denev P, Eftimov M, Georgieva A, Kuzmanova V, Kuzmanov A, Kuzmanov K, Tzaneva M. Protective effects of Aronia melanocarpa juices either alone or combined with extracts from Rosa canina or Alchemilla vulgaris in a rat model of indomethacin-induced gastric ulcers. Food Chem Toxicol 2019; 132:110739. [PMID: 31374297 DOI: 10.1016/j.fct.2019.110739] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Revised: 07/23/2019] [Accepted: 07/29/2019] [Indexed: 02/06/2023]
Abstract
The aim of the study was to investigate the effects of four Aronia melanocarpa-based juices in a rat model of indomethacin-induced gastric ulceration. THE JUICES WERE: AM1 and AM2 (produced from aronia fruits at 20 °C and 60 °C, respectively), AMRC (a mixture of AM2 with Rosa canina extract) and AMAV (aronia juice with Alchemilla vulgaris). Male Wistar rats were used. Each of the juices (10 ml/kg) was administered for 10 days. Indomethacin (30 mg/kg) was injected subcutaneously and after 4 h, the effects were estimated. Indomethacin caused heavy destructions of the gastric mucosa, increased the expression of Bax and decreased the expression of Bcl-2, induced a certain increase in lipid peroxidation and a slight decrease in gastric PGE2 content. The pretreatment with the juices reduced the severity of indomethacin-induced gastric lesions and antagonized the effects of indomethacin on apoptosis and lipid peroxidation. The highest was the protective effect of AMAV, the juice with the highest polyphenolic content. The protective effect of Aronia melanocarpa-based juices against indomethacin-induced gastric lesions could be attributed to their polyphenolic contents. The mechanism involved to the highest extent in the protective effect of the juices was the inhibition of apoptosis.
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Affiliation(s)
- Stefka Valcheva-Kuzmanova
- Department of Pharmacology and Clinical Pharmacology and Therapeutics, Medical University Prof. Dr. Paraskev Stoyanov, Varna, Bulgaria.
| | - Petko Denev
- Laboratory of Biologically Active Substances, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Plovdiv, Bulgaria
| | - Miroslav Eftimov
- Department of Pharmacology and Clinical Pharmacology and Therapeutics, Medical University Prof. Dr. Paraskev Stoyanov, Varna, Bulgaria
| | - Antoaneta Georgieva
- Department of Pharmacology and Clinical Pharmacology and Therapeutics, Medical University Prof. Dr. Paraskev Stoyanov, Varna, Bulgaria
| | | | - Atanas Kuzmanov
- Medical University Prof. Dr. Paraskev Stoyanov, Varna, Bulgaria
| | - Krasimir Kuzmanov
- Vivarium, Medical University Prof. Dr. Paraskev Stoyanov, Varna, Bulgaria
| | - Maria Tzaneva
- Department of General and Clinical Pathology, Forensic Medicine and Deontology, Medical University Prof. Dr. Paraskev Stoyanov, Varna, Bulgaria
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Paulrayer A, Adithan A, Lee JH, Moon KH, Kim DG, Im SY, Kang CW, Kim NS, Kim JH. Aronia melanocarpa (Black Chokeberry) Reduces Ethanol-Induced Gastric Damage via Regulation of HSP-70, NF-κB, and MCP-1 Signaling. Int J Mol Sci 2017; 18:ijms18061195. [PMID: 28587230 PMCID: PMC5486018 DOI: 10.3390/ijms18061195] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Revised: 05/15/2017] [Accepted: 05/17/2017] [Indexed: 01/02/2023] Open
Abstract
Aronia melanocarpa (Michx.) Ell. belongs to the Rosaceae family. The purpose of this study is to explore the gastroprotective effect of the Aronia melanocarpa hydro-alcoholic extract (AMHAE) against ethanol-induced gastric ulcer in a rat model. Different concentrations (50, 100, and 200 mg/kg) of AMHAE, or 30 mg/kg of omeprazole, significantly inhibited the gastric injury formation. The ethanol-induced ulcer group showed significant increases of malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, nuclear factor-kappaB p65 (NF-κB p65), and monocyte chemoattractant protein (MCP)-1, and decreased activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-px), and interleukin (IL)-4. However, AMHAE (200 mg/kg) pretreatment significantly reversed the altered pathophysiological levels of these biomolecules to near normal stages. The gastroprotective activity of AMHAE was abolished by pretreatment with l-NAME, naloxone, capsazepine, and indomethacin, demonstrating the participation of nitric oxide (NO), opioids, TRPV (vanilloid receptor-related transient receptor potential), and prostaglandins in AMHAE-assisted gastroprotection against ethanol-induced gastric injuries. This gastroprotective effect of AMHAE might be due to the downregulation of TNF-α-based NF-κB, MCP-1 signaling and strong antioxidant properties.
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Affiliation(s)
- Antonisamy Paulrayer
- College of Veterinary Medicine, BK21PLUS project, Chonbuk National University, 79 Gobong-ro, Iksan-city, Jeollabuk-do 54596, Korea.
| | - Aravinthan Adithan
- College of Veterinary Medicine, BK21PLUS project, Chonbuk National University, 79 Gobong-ro, Iksan-city, Jeollabuk-do 54596, Korea.
| | - Jeong Ho Lee
- Sunchang Reserch Institute of Health and Longevity, Ingye-myeon Indeok-ro, Sunchang-gun, Jeollabuk-do 56015, Korea.
| | - Kwang Hyun Moon
- Sunchang Reserch Institute of Health and Longevity, Ingye-myeon Indeok-ro, Sunchang-gun, Jeollabuk-do 56015, Korea.
| | - Dae Geun Kim
- Sunchang Reserch Institute of Health and Longevity, Ingye-myeon Indeok-ro, Sunchang-gun, Jeollabuk-do 56015, Korea.
| | - So Yeon Im
- Sunchang Reserch Institute of Health and Longevity, Ingye-myeon Indeok-ro, Sunchang-gun, Jeollabuk-do 56015, Korea.
| | - Chang-Won Kang
- College of Veterinary Medicine, BK21PLUS project, Chonbuk National University, 79 Gobong-ro, Iksan-city, Jeollabuk-do 54596, Korea.
| | - Nam Soo Kim
- College of Veterinary Medicine, BK21PLUS project, Chonbuk National University, 79 Gobong-ro, Iksan-city, Jeollabuk-do 54596, Korea.
| | - Jong-Hoon Kim
- College of Veterinary Medicine, BK21PLUS project, Chonbuk National University, 79 Gobong-ro, Iksan-city, Jeollabuk-do 54596, Korea.
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Golyshkin DV, Falalyeyeva TM, Neporada KS, Beregova TV. [THE INFLUENCE OF MELANIN ON THE GASTRIC MUCOSA AND HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL AXIS UNDER ACUTE STRESS CONDITIONS]. ACTA ACUST UNITED AC 2015; 61:65-72. [PMID: 26387162 DOI: 10.15407/fz61.02.065] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
We studied the influence of melanin from yeast-like fungi Nadsoniella nigra strain X1 on the changes of the levels of adrenocorticotropic hormone (ACTH) and cortisol in blood serum of rats, adrenal glands weight ratio and lesions of the gastric mucosa (GM) caused by neuromuscular tension by Selye. Melanin administration restored functioning of the hypothalamic-pituitary-adrenal axis that was evident by an increase of ACTH concentration by 42% and a decrease of cortisol concentration by 19% compared to the rats injected with water (group 2). In rats treated with melanin, the adrenal glands weight ratio, didn't differ from intact control group of the rats. Melanin decreased ulcers area by 64% and reduced the content of free hydroxyproline by 29%, the free fucose by 16% and the free hexuronic acids by 24% in the GM compared to the group 2 of the rats. It is established that the mechanism of melanin stress-protective properties are based on its regulation of the glucocorticoids secretion and prevention of GM collagen and extracellular matrix substances depolymerization. Melanin possesses gastroprotective properties and is a perspective agent for preventing and treatment of consequences of the stress influence on the organism.
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7
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Tirmenstein M, Horvath J, Graziano M, Mangipudy R, Dorr T, Colman K, Zinker B, Kirby M, Cheng PTW, Patrone L, Kozlosky J, Reilly TP, Wang V, Janovitz E. Utilization of the Zucker Diabetic Fatty (ZDF) Rat Model for Investigating Hypoglycemia-related Toxicities. Toxicol Pathol 2015; 43:825-37. [PMID: 26085543 DOI: 10.1177/0192623315581020] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Glucokinase (GK) catalyzes the initial step in glycolysis and is a key regulator of glucose homeostasis. Therefore, glucokinase activators (GKa) have potential benefit in treating type 2 diabetes. Administration of a Bristol-Myers Squibb GKa (BMS-820132) to healthy euglycemic Sprague-Dawley (SD) rats and beagle dogs in 1 mo toxicology studies resulted in marked and extended hypoglycemia with associated clinical signs of toxicity and degenerative histopathological changes in the stomach, sciatic nerve, myocardium, and skeletal muscles at exposures comparable to those expected at therapeutic clinical exposures. To investigate whether these adverse effects were secondary to exaggerated pharmacology (prolonged hypoglycemia), BMS-820132 was administered daily to male Zucker diabetic fatty (ZDF) rats for 1 mo. ZDF rats are markedly hyperglycemic and insulin resistant. BMS-820132 did not induce hypoglycemia, clinical signs of hypoglycemia, or any of the histopathologic adverse effects observed in the 1 mo toxicology studies at exposures that exceeded those observed in SD rats and dogs. This indicates that the toxicity observed in euglycemic animals was secondary to the exaggerated pharmacology of potent GK activation. This study indicates that ZDF rats, with conventional toxicity studies, are a useful disease model for testing antidiabetic agents and determining toxicities that are independent of prolonged hypoglycemia.
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Affiliation(s)
- Mark Tirmenstein
- Bristol-Myers Squibb, Drug Safety Evaluation, New Brunswick, New Jersey, USA
| | - Joseph Horvath
- Bristol-Myers Squibb, Drug Safety Evaluation, New Brunswick, New Jersey, USA
| | - Michael Graziano
- Bristol-Myers Squibb, Drug Safety Evaluation, Princeton, New Jersey, USA
| | - Raja Mangipudy
- Bristol-Myers Squibb, Drug Safety Evaluation, New Brunswick, New Jersey, USA
| | - Thomas Dorr
- Bristol-Myers Squibb, Drug Safety Evaluation, New Brunswick, New Jersey, USA
| | - Karyn Colman
- Bristol-Myers Squibb, Drug Safety Evaluation, New Brunswick, New Jersey, USA Present affiliation: Novartis Institutes for BioMedical Research, East Hanover, New Jersey, USA
| | - Bradley Zinker
- Bristol-Myers Squibb, Discovery Biology, Pennington, New Jersey, USA
| | - Mark Kirby
- Bristol-Myers Squibb, Discovery Biology, Pennington, New Jersey, USA Present affiliation: Lilly China Research and Development Center, Shanghai, China
| | - Peter T W Cheng
- Bristol-Myers Squibb, Discovery Chemistry, Pennington, New Jersey, USA
| | - Laura Patrone
- Bristol-Myers Squibb, Drug Safety Evaluation, New Brunswick, New Jersey, USA
| | - John Kozlosky
- Bristol-Myers Squibb, Drug Safety Evaluation, New Brunswick, New Jersey, USA
| | - Timothy P Reilly
- Bristol-Myers Squibb, Exploratory Clinical and Translational Research, Princeton, New Jersey, USA
| | - Victor Wang
- Bristol-Myers Squibb, Drug Safety Evaluation, New Brunswick, New Jersey, USA
| | - Evan Janovitz
- Bristol-Myers Squibb, Discovery Toxicology, Pennington, New Jersey, USA
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Protective effects of friedelin isolated from Azima tetracantha Lam. against ethanol-induced gastric ulcer in rats and possible underlying mechanisms. Eur J Pharmacol 2015; 750:167-75. [DOI: 10.1016/j.ejphar.2015.01.015] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Revised: 12/23/2014] [Accepted: 01/05/2015] [Indexed: 11/21/2022]
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9
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Antonisamy P, Subash-Babu P, Alshatwi AA, Aravinthan A, Ignacimuthu S, Choi KC, Kim JH. Gastroprotective effect of nymphayol isolated from Nymphaea stellata (Willd.) flowers: contribution of antioxidant, anti-inflammatory and anti-apoptotic activities. Chem Biol Interact 2014; 224:157-63. [PMID: 25289771 DOI: 10.1016/j.cbi.2014.09.020] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Revised: 08/23/2014] [Accepted: 09/23/2014] [Indexed: 01/07/2023]
Abstract
Gastric ulcer is an illness that affects a great number of people worldwide. The goal of the present research was to assess the anti-ulcerogenic activity of nymphayol (NYM), isolated from Nymphaea stellata, against an ethanol-induced ulcer model in rats. Administration of ethanol elevates the levels of the ulcer index (UI) along with causing tremendous increases in lipid peroxidation and myeloperoxidase (MPO) and significant decreases in gastric mucus, catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and prostaglandin E2 (PGE2). However, the NYM- (45 mg/kg) pretreated animals showed considerable increases in antioxidants, gastric mucus, and PGE2 level and significant decreases in UI, lipid peroxidation, and MPO level. Pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were increased and the level of interleukin-10 (IL-10), an anti-inflammatory cytokine, was decreased in ethanol-induced ulcerated animals, and these inequalities were amended by NYM pretreatment. Pro-apoptotic markers including caspase-8, caspase-9, and caspase-3 were decreased and Bcl-2, an anti-apoptotic marker, was increased through NYM pretreatment, as compared with the ethanol-induced ulcer group. Pretreatment with indomethacin, SC560, rofecoxib, and Nω-Nitro-L-arginine methyl ester (L-NAME) considerably prevented the ulcer protective activity of NYM (45 mg/kg), indicating the involvement of cyclooxygenase (COX) and nitric oxide synthase (NOS) in NYM-mediated gastroprotection against ethanol-induced ulcer. These outcomes suggest that the gastroprotective effect of NYM might be mediated by adjustment of inflammatory mediators and apoptotic markers and increasing antioxidants.
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Affiliation(s)
- Paulrayer Antonisamy
- Department of Veterinary Physiology, College of Veterinary Medicine, Chonbuk National University, Biosafety Research Institute, 664-14, 1GA, Duckjin-Dong, Duckjin-Gu, Jeonju City, Jeollabuk-Do 561-756, Republic of Korea
| | - Pandurangan Subash-Babu
- Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food and Agricultural Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Ali A Alshatwi
- Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food and Agricultural Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Adithan Aravinthan
- Department of Veterinary Physiology, College of Veterinary Medicine, Chonbuk National University, Biosafety Research Institute, 664-14, 1GA, Duckjin-Dong, Duckjin-Gu, Jeonju City, Jeollabuk-Do 561-756, Republic of Korea
| | - Savarimuthu Ignacimuthu
- Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600 034, Tamil Nadu, India
| | - Ki Choon Choi
- Grassland and Forage Division, National Institute of Animal Science, RDA, Seonghwan-Eup, Cheonan-Si, Chungnam 330-801, Republic of Korea
| | - Jong-Hoon Kim
- Department of Veterinary Physiology, College of Veterinary Medicine, Chonbuk National University, Biosafety Research Institute, 664-14, 1GA, Duckjin-Dong, Duckjin-Gu, Jeonju City, Jeollabuk-Do 561-756, Republic of Korea.
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Gastroprotective activity of violacein isolated from Chromobacterium violaceum on indomethacin-induced gastric lesions in rats: investigation of potential mechanisms of action. ScientificWorldJournal 2014; 2014:616432. [PMID: 25162059 PMCID: PMC4138890 DOI: 10.1155/2014/616432] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2014] [Revised: 06/18/2014] [Accepted: 06/26/2014] [Indexed: 12/21/2022] Open
Abstract
Chromobacterium violaceum, Gram-negative bacteria species found in tropical regions of the world, produces a distinct deep violet-colored pigment called violacein. In the present study, we investigated whether violacein can promote a gastroprotective effect and verified the possible mechanisms involved in this action. For this study, an indomethacin-induced gastric ulcer rat model was used. The roles of biomolecules such as MPO, PGE2, pro- and anti-inflammatory cytokines, growth factors, caspase-3, NO, K+ATP channels, and α2-receptors were investigated. Violacein exhibited significant gastroprotective effect against indomethacin-induced lesions, while pretreatment with L-NAME and glibenclamide (but not with NEM or yohimbine) was able to reverse this action. Pretreatment with violacein also restored cNOS level to normal and led to attenuation of enhanced apoptosis and gastric microvascular permeability. Our results suggest that violacein provides a significant gastroprotective effect in an indomethacin-induced ulcer model through the maintenance of some vital protein molecules, and this effect appears to be mediated, at least in part, by endogenous prostaglandins, NOS, K+ATP channel opening, and inhibition of apoptosis and gastric microvascular permeability.
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11
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Angiotensin (1–7) protects against stress-induced gastric lesions in rats. Biochem Pharmacol 2014; 87:467-76. [DOI: 10.1016/j.bcp.2013.10.026] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2013] [Revised: 10/29/2013] [Accepted: 10/31/2013] [Indexed: 10/26/2022]
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Yan B, Shi J, Xiu LJ, Liu X, Zhou YQ, Feng SH, Lv C, Yuan XX, Zhang YC, Li YJ, Wei PK, Qin ZF. Xiaotan Tongfu granules contribute to the prevention of stress ulcers. World J Gastroenterol 2013; 19:5473-5484. [PMID: 24023490 PMCID: PMC3761100 DOI: 10.3748/wjg.v19.i33.5473] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2013] [Revised: 06/28/2013] [Accepted: 07/17/2013] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the efficacy and potential mechanism of Xiaotan Tongfu granules (XTTF) in stress ulcers. METHODS One hundred sixty rats were randomly divided into 4 groups (n = 10) as follows: the model group (MP group), the control group (CP group), the ranitidine group (RP group) and the XTTF granule group (XP group). Rats in the MP group received no drugs, rats in the CP group received 0.2 mL of a 0.9% sodium chloride solution via oral gavage, and rats in the RP and XP groups received the same volume of ranitidine (50 mg/kg) or XTTF granule (4.9 g/kg). The cold-restraint stress model was applied to induce stress ulcers after 7 consecutive days of drug administration. Afterwards, rats were sacrificed at 0, 3, 6 and 24 h. Gastric pH was measured by a precise pH meter; gastric emptying rate (GER) was measured by using a methylcellulose test meal; myeloperoxidase activity (MPO), macrophage migration inhibitory factor (MIF), proliferating cell nuclear antigen (PCNA), and heat shock protein 70 (HSP70) were measured by immunohistochemical staining; and mucosal cell apoptosis was measured by transferase dUTP nick end labeling. RESULTS In the cold-restraint stress model, the development of stress ulcers peaked at 3 h and basically regressed after 24 h. Gastric lesions were significantly different in the RP and XP groups at each time point. Interestingly, although this index was much lower in the RP group than in the XP group immediately following stress induction (7.00 ± 1.10 vs 10.00 ± 1.79, P < 0.05. Concerning gastric pH, between the RP and XP groups, we detected a statistically significant difference immediately after stress induction (0 h: 4.56 ± 0.47 vs 3.34 ± 0.28, P < 0.05) but not at any of the subsequent time points. For GER, compared to the RP group, GER was remarkably elevated in the XP group because a statistically significant difference was detected (3 h: 46.84 ± 2.70 vs 61.16 ± 5.12, P < 0.05; 6 h: 60.96 ± 6.71 vs 73.41 ± 6.16, P < 0.05; 24 h: 77.47 ± 3.17 vs 91.31 ± 4.34, P < 0.05). With respect to MPO and MIF, comparisons between the RP and XP groups revealed statistically significant differences at 3 h (MPO: 18.94 ± 1.20 vs 13.51 ± 0.89, P < 0.05; MIF: 150.67 ± 9.85 vs 122.17 ± 5.67, P < 0.05) and 6 h (MPO: 13.22 ± 1.54 vs 8.83 ± 0.65, P < 0.05; MIF: 135.50 ± 9.46 vs 109.83 ± 6.40, P < 0.05). With regard to HSP70, HSP70 expression was significantly increased in the RP and XP groups at 3 and 6 h compared to the MP and CP groups. In addition, comparing the RP and XP groups also showed statistically significant differences at 3 and 6 h. The expression of PCNA was higher in the RP and XP groups 3 h after stress induction. Between these two groups, small but statistically significant differences were observed at all of the time points (3 h: 69.50 ± 21.52 vs 79.33 ± 15.68, P < 0.05; 6 h: 107.83 ± 4.40 vs 121.33 ± 5.71, P < 0.05; 24 h: 125.33 ± 5.65 vs 128.50 ± 14.49, P < 0.05) except 0 h. With regard to apoptosis, the apoptotic activity in the RP and XP groups was significantly different from that in the MP and CP groups. The XP group exhibited a higher inhibition of cell apoptosis than the RP group at 3 h (232.58 ± 24.51 vs 174.46 ± 10.35, P < 0.05) and 6 h (164.74 ± 18.31 vs 117.71 ± 12.08, P < 0.05). CONCLUSION The Xiaotan Tongfu granule was demonstrated to be similar to ranitidine in preventing stress ulcers. It exhibited multiple underlying mechanisms and deserves further study.
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Iijima K, Iwabuchi T, Ara N, Koike T, Shinkai H, Kamata Y, Ichikawa T, Ishihara K, Shimosegawa T. Reactive increase in gastric mucus secretion is an adaptive defense mechanism against low-dose aspirin-induced gastropathy. Dig Dis Sci 2013; 58:2266-74. [PMID: 23649375 DOI: 10.1007/s10620-013-2660-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2013] [Accepted: 03/20/2013] [Indexed: 01/28/2023]
Abstract
BACKGROUND Gastric mucus is considered to play an essential role in gastric mucosal defense mechanisms, especially when irritants are present in the stomach. AIM To investigate the relationship between low-dose aspirin-induced gastropathy and gastric secretory function, especially gastric mucus secretion, in healthy volunteers. METHODS Thirty male, asymptomatic, Helicobacter pylori pylori-negative healthy volunteers were asked to take 100 mg of enteric-coated aspirin (Bayaspirin) once a day for 10 days. Endoscopic examination was performed before and 3 and 10 days after drug administration. The extent of endoscopically assessed gastric mucosal injury was semi-quantitatively evaluated according to the modified Lanza score. The pentagastrin-stimulated gastric juice was collected for 10 min during the endoscopic examination and subjected to analysis for gastric acid (mEq/10 min) or mucus (mg hexose/10 min) output. RESULTS Overall, the 10-day aspirin treatment significantly increased gastric mucus secretion from 0.8 (interquartile range 1.7) to 1.6 (1.6) mg hexose/10 min (P < 0.05), with a concomitant and significant decrease in the gastric acid/mucus ratio from 4.3 (5.2) to 2.9 (4.7) (P < 0.01). Subsequent analysis of two subgroups of volunteers categorized according to their endoscopic status ("severe gastropathy" vs. "modest gastropathy") revealed that changes in gastric secretory parameters occurred exclusively in those subjects without severe gastric injury; there was no alteration in these parameters in subjects with severe gastric injury. CONCLUSIONS The results of this study suggest that the reactive increase in gastric mucus secretion is an adaptive defense mechanism against low-dose aspirin-induced gastropathy. In some individuals, such a response may be insufficient to prevent the development of severe mucosal injury and even ulcers and their complications.
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Affiliation(s)
- K Iijima
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, Miyagi, 980-8574, Japan.
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Abshenas J, Kheirandish R, Salary AR. Gastroprotective effect of mummy on induced gastric ulcer in rats. ACTA ACUST UNITED AC 2012. [DOI: 10.1007/s00580-012-1610-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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15
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Mei X, Xu D, Xu S, Zheng Y, Xu S. Novel role of Zn(II)-curcumin in enhancing cell proliferation and adjusting proinflammatory cytokine-mediated oxidative damage of ethanol-induced acute gastric ulcers. Chem Biol Interact 2012; 197:31-9. [PMID: 22465177 DOI: 10.1016/j.cbi.2012.03.006] [Citation(s) in RCA: 108] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2011] [Revised: 02/26/2012] [Accepted: 03/11/2012] [Indexed: 12/16/2022]
Abstract
Alcohol consumption can induce gastric ulcers and zinc deficiency. Zinc complexes were reported to have anti-ulcer activity as it acts as an anti-inflammatory and antioxidant. Zn(II)-curcumin complex and its solid dispersions (SDs) were synthesized and evaluated for its gastroprotective activity and mechanism against ethanol-induced ulcer. The Swiss murine fibroblast cell line (3T3) was used as an alternative in vitro model to evaluate the effects of Zn(II)-curcumin on cell proliferation. Zn(II)-curcumin were administered orally for seven consecutive days prior to induction of ulcers using ethanol. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that solid dispersions (SDs) of Zn(II)-curcumin (2.5-20 μM) enhanced the proliferation of 3T3 cells more significantly than curcumin at the same concentrations (P<0.01). Oral administration of Zn(II)-curcumin (12, 24 and 48 mg/kg) SDs dose-dependently prevented formation of ulcer lesions induced by ethanol. The levels of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and oxidative stress superoxide dismutase (SOD), glutathione peroxidase (GPX-Px), malonaldehyde (MDA) and H(+)-K(+)-ATPase were in the rats exposed to ethanol in ulceration have been altered. Zn(II)-curcumin prevented formation of ulcer lesions, significantly inhibited TNF-α and IL-6 mRNA expression, increased the activity of SOD and GSH-Px, reduced MDA levels and H(+)-K(+)-ATPase in mucosa of rats compared to controls (P<0.05). These findings suggest that the gastroprotective activity of Zn(II)-curcumin complex might contribute in stimulating cell proliferation and adjusting the proinflammatory cytokine-mediated oxidative damage to the gastric mucosa.
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Affiliation(s)
- Xueting Mei
- Laboratory of Traditional Chinese Medicine and Marine Drugs, Department of Biochemistry, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China
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16
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Gastroprotective and antidepressant effects of a new zinc(II)–curcumin complex in rodent models of gastric ulcer and depression induced by stresses. Pharmacol Biochem Behav 2011; 99:66-74. [DOI: 10.1016/j.pbb.2011.04.002] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2010] [Revised: 03/29/2011] [Accepted: 04/04/2011] [Indexed: 12/27/2022]
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17
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Khalefa AA, Abd-Alaleem DI, Attiaa KI. The protective effects of ghrelin and leptin against stress-induced gastric ulcer in rats. Arab J Gastroenterol 2010. [DOI: 10.1016/j.ajg.2010.04.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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18
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Uslu E, Aydin S, Carkman S, Uzun H, Altinli E, Apaydin BB, Memisoglu K, Erginoz E. Effects of gender on stress ulcer formation in rats. TOHOKU J EXP MED 2002; 197:17-26. [PMID: 12180789 DOI: 10.1620/tjem.197.17] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
In the experimental stress literature, the results of investigations have not shown a specific sex-dependent vulnerability to stress ulceration. The aim of this study was to evaluate the importance of sex differences on stress ulcer development. Related to gender, the contributing factors for stress ulcer production such as luminal acidity, sialic acid as an marker of gastric mucosal protection, oxygen (O2)-derived free radicals and endogenous antioxidant defence mechanisms were also investigated. Fifty Wistar Albino rats weighing about 230 g and aged 7 or 8 months were divided equally into five groups: Group I normal male rats, group II castrated male rats, group III normal female rats in estrus phase, group IV normal female rats in diestrus phase and group V castrated female rats. Cold restraint model was used for 6 hours to produce stress ulcer. No statistically significant difference was found out between groups in view of gross and histopathologic damage. There was no significant difference between groups according to gastric luminal acidity, gastric mucosal sialic acid, gastric malonaldehyde (MDA) and catalase values. Gastric superoxide dismutase (SOD) activity was significantly lower in Group I in comparison to those of Group III and IV. Sex differences do not interfere stress ulcer formation. SOD activity in rat gastric tissue has varied significantly by hormonal milieu.
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Affiliation(s)
- Ezel Uslu
- Department of Biochemistry, Cerrahpaşa Medical Faculty, Istanbul University, Bahcesehir, Turkey.
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19
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Martínez-Augustín O, Sánchez de Medina F, Sánchez de Medina F. Effect of psychogenic stress on gastrointestinal function. J Physiol Biochem 2000; 56:259-74. [PMID: 11198163 DOI: 10.1007/bf03179794] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
This review summarizes the studies published over the last twenty years on the effects of psychogenic stress on gastrointestinal function, using animal models. The effects of stress on gastric ulceration have received wide attention and the central and local mechanisms of mucosal damage have been, for the most part, clearly delineated. In comparison, relatively few studies have focused on the impact of stress on intestinal and colonic physiology, even though its influence on intestinal motility, mucosal permeability and inflammation has been established. More work is necessary in this field, especially considering the importance of irritable bowel syndrome in modern society.
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Affiliation(s)
- O Martínez-Augustín
- Department of Biochemistry and Molecular Biology, University of Granada, School of Pharmacy, Spain
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20
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Abstract
Although propranolol has been shown to protect against ethanol and stress ulceration, the antiulcer mechanisms are still unclear. The present study examined the antiulcer mechanisms of propranolol in three different types of ulceration induced respectively by ethanol (60%), indomethacin (30 mg/kg) and stress (cold-restraint). Propranolol pretreatment in the highest dose (10 mg/kg) given either intraperitoneally (i.p.) or orally (p.o.) prevented gastric mucosal damage in these three ulcer models. The three doses of the drug (2.5, 5 or 10 mg/kg) dose-dependently decreased systemic blood pressure which was accompanied by a reduction of gastric mucosal blood flow. These findings suggest that the protection was unrelated to an improvement of local circulation in the stomach. However, propranolol preserved the mucus levels in the three types of ulcer models. The beta-adrenoceptor blocker also increased the basal gastric mucosal potential difference. These findings indicate that propranolol strengthens the mucosal barrier by the preservation of mucosal mucus and enhancement of the mucosal integrity in the stomach.
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Affiliation(s)
- S K Kaan
- Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong Kong
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21
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Singla AK, Wadhwa H. Zinc-aspirin complex: synthesis, physicochemical and biological evaluation. Int J Pharm 1994. [DOI: 10.1016/0378-5173(94)90126-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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22
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Abstract
BACKGROUND Fasting during the month of Ramadan provides researchers with a good opportunity to study experimental hunger. METHODS The case histories of patients brought to Ankara Numune Hospital and hospitalized there because of peptic ulcer complaints during the period 1987-92 were retrospectively studied. RESULTS The ratio of peptic ulcer complications was in all the years of the study higher during Ramadan than during the periods before Ramadan (0.05 > p > 0.01) and after Ramadan (0.1 > p > 0.05). Female patients tended to develop more haemorrhage and perforations during Ramadan. In the peptic ulcer perforation group the average age of women was significantly higher during Ramadan, whereas it was significantly lower in men. CONCLUSIONS A type of partial hunger during Ramadan increased peptic ulcer complications.
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Affiliation(s)
- O Dönderici
- Second and Third Internal Disease Clinics, Ankara Numune Hospital, Turkey
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23
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Azuumi Y, Ichikawa T, Ishihara K, Hotta K. The validity of the ethanol precipitation method for the measurement of mucin content in human gastric juices and its possible relationship to gastroduodenal diseases. Clin Chim Acta 1993; 221:219-25. [PMID: 8149639 DOI: 10.1016/0009-8981(93)90037-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Affiliation(s)
- Y Azuumi
- Department of Internal Medicine, Kitasato University School of Medicine, Kanagawa, Japan
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24
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Massoud TF, Nolan DJ. Morning or afternoon barium meal? Diurnal variation and the effectiveness of gastric mucosal coating during double-contrast studies. Clin Radiol 1990; 42:407-9. [PMID: 2261719 DOI: 10.1016/s0009-9260(05)80895-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The radiographs of 60 patients having double-contrast barium meal examinations were analysed by a linear analogue technique to assess variation in the quality of mucosal coating between morning and afternoon studies. No significant difference (P greater than 0.5) was found between morning and afternoon gastric mucosal coating. Factors that could in theory contribute to a diurnal variation are discussed. We conclude that afternoon DCBMs can be confidently booked and performed, in the knowledge that their diagnostic quality is not impaired.
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Affiliation(s)
- T F Massoud
- Department of Radiology, John Radcliffe Hospital, Oxford
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25
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Bakke HK, Walther BT. Paradoxical DSP-4 effects: protection against gastric erosions and depletion of mucosal glycoproteins. Brain Res 1990; 517:301-7. [PMID: 2375999 DOI: 10.1016/0006-8993(90)91041-e] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
We have previously reported that rats pretreated with the central noradrenergic neurotoxin DSP-4 are protected against 23 h restraint-induced gastric erosions. To elucidate the peripheral mechanisms of this protection, we undertook direct biochemical analyses of the gastric mucosa in terms of glycoproteins and proteins. A simple method for preparation of gastric mucosa devoid of the muscular stomach wall tissue is described. A restraint-induced decrease in gastric mucosal wet weight and mucosal glycoprotein content was revealed. Restraint had no effect on mucosal protein content, and no changes were found in gastric wall glycoprotein or protein content. Despite showing protection against restraint-induced gastric erosions, unrestrained DSP-4-treated animals exhibited reduced mucosal wet weight and mucosal glycoprotein content when compared to unrestrained controls. After the stress period, no significant differences on mucosal weight or glycoproteins could be detected between control and DSP-4-treated animals. The results indicate that the protective effect of DSP-4 in this paradigm is not due to enhanced gastric mucosal protection against erosive factors. We suggest that an additional effect of central nervous NA depletion by DSP-4 may be elimination of aggressive factors which precipitate overt ulcers.
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Affiliation(s)
- H K Bakke
- Institute of Physiological Psychology, University of Bergen, Norway
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26
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Semble EL, Wu WC, Castell DO. Nonsteroidal antiinflammatory drugs and esophageal injury. Semin Arthritis Rheum 1989; 19:99-109. [PMID: 2683094 DOI: 10.1016/0049-0172(89)90054-1] [Citation(s) in RCA: 50] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Affiliation(s)
- E L Semble
- Department of Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27103
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27
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Semble EL, Wu WC. Prostaglandins in the gut and their relationship to non-steroidal anti-inflammatory drugs. BAILLIERE'S CLINICAL RHEUMATOLOGY 1989; 3:247-69. [PMID: 2670254 DOI: 10.1016/s0950-3579(89)80020-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Prostaglandins are long-chain, saturated, oxygenated fatty acids. Relatively large quantities of prostaglandins have been found in gut mucosa, suggesting that these substances play an important role in gastrointestinal physiology. Non-steroidal anti-inflammatory drugs (NSAIDs) cause damage to the gastric, intestinal, and colonic mucosa in experimental animals and in humans. Prostaglandins protect the gastric mucosa against injury induced by NSAIDs, and this property has been labelled cytoprotection. The mechanisms of cytoprotection have been extensively evaluated and are probably multifactorial, including effects on the gastric mucosal barrier, gastric blood flow, mucus, bicarbonate, and fluid section, ionic transport, cyclic AMP, and surface-active phospholipids. Prostaglandins may also prevent NSAID-induced injury in the small intestine and colon. The mechanisms responsible for prostaglandin protection in the lower gut against injurious agents are unknown. Further studies of the role of prostaglandins in the gut and their relationship to the effects of NSAIDs are needed. The results of these investigations may lead to a better understanding of the importance of prostaglandins in the physiology of the gastrointestinal tract, and may provide information regarding actions of NSAIDs on the functional integrity of the gastric, intestinal, and colonic mucosa.
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28
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Abstract
The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the gastric mucosa are well documented. The complex mechanisms of gastric damage, however, are not fully understood. This review examines current knowledge about the normal function of the gastric mucosal barrier; the role of prostaglandins in cytoprotection and repair; the mechanisms by which aspirin and other weak organic acids are absorbed by the stomach; and the subsequent cascade of events--including ion trapping and back diffusion of hydrogen ions--that leads to gastric erosion and bleeding. A hypothesis describing NSAIDs' dual insult on the stomach is advanced.
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Affiliation(s)
- R T Schoen
- Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510
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29
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Matsumoto A, Asada S, Saitoh O, Tei H, Okumura Y, Hirata I, Ohshiba S. A study on gastric ulcers induced by long-term fasting in rats. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. SUPPLEMENT 1989; 162:75-8. [PMID: 2595313 DOI: 10.3109/00365528909091129] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
The present study was performed to investigate the roles of intragastric pH and PAS positive mucus as to the incidence of gastric ulcers after long-term fasting in rats. Gastric ulcers in the forestomach and corpus were found at 4 and 6 days after fasting, respectively. The intragastric pH was significantly reduced at 1, 2, 3, 4, 6 and 7 days after fasting, but tended to have returned to control levels at 8 days. PAS positive mucus was significantly increased at 2 to 7 days, but there was no significant change at 8 days. From these results, it seems that the aggressive factor is not involved, but attenuation of the defensive factor is important as to the incidence of this type of ulcer. As one of the causes of this attenuation, a decrease in the gastric mucus volume was suggested.
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Affiliation(s)
- A Matsumoto
- Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan
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30
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Abstract
The effect of cimetidine on normal human gastric mucus has been compared with that of carbenoxolone, a drug believed to enhance mucus production. Each drug was given for two weeks, the gastric contents aspirated over a timed period and the results assessed in unstimulated and pentagastrin stimulated secretions. The volume, dry weight and the carbohydrate contents of non-diffusable glycoconjugates, high molecular mass glycoproteins and glycopolypeptides were investigated. Both drugs reduced the volumes of stimulated secretions. This was statistically significant after cimetidine. More importantly neither drug affected the amount of non-diffusable glycoconjugates, so that the concentration remained the same or increased. Both drugs reduced the monosaccharide content of the high molecular mass fractions. This reached significance for the stimulated secretion after cimetidine. As the carbohydrate content of the glycopolypeptides was unchanged this indicated the presence of a non-mucin glycoprotein or protein. Overall there was no fundamental difference between the results for cimetidine and carbenoxolone.
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Affiliation(s)
- M D Ene
- Department of Medicine, University of Port Harcourt, Nigeria
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31
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Miñano FJ, Serrano JS, Pascual J, Sancibrián M. Effects of GABA on gastric acid secretion and ulcer formation in rats. Life Sci 1987; 41:1651-8. [PMID: 3041149 DOI: 10.1016/0024-3205(87)90734-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
The effects of gamma-aminobutyric acid (GABA), bicuculline and baclofen, orally and intraperitoneally (i.p.) administered, on the development of stress and pyloric ligation-induced gastric ulcers, were studied in rats. GABA, but not baclofen, significantly reduced the frequency and severity of both models as assessed by ulcer index, incidence and number of ulcers/animal. Gastric protection was dose-related in both experimental models and was completely antagonized by pretreatment with bicuculline methiodide, that blocks peripheral, but not central GABA receptors. All GABA effects were observed after oral and i.p. administration, but inhibition of gastric lesions was greater by the last route. Furthermore, GABA did not affect the acidity or the volume of gastric secretion in pylorus-ligated rats. Consequently its antiulcer activity appears to be mediated by factors unrelated to gastric acid secretion. Since the entry of GABA across blood-brain barrier is greatly restricted it may be concluded that stimulation of peripheral GABA receptors is primarily involved in its antiulcer action.
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32
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33
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Somasundaram K, Ganguly AK. Gastric mucosal defence mechanism during stress of pyloric obstruction in albino rats. Clin Exp Pharmacol Physiol 1987; 14:309-18. [PMID: 3665196 DOI: 10.1111/j.1440-1681.1987.tb00976.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
1. The integrity of the gastric mucosa and its ability to secrete mucus are believed to be essential for protection of gastric mucosa against ulceration induced by aggressive factors active in any stress situation. This study involves a three-compartmental analysis of gastric mucosal barrier in pylorus-ligated albino rats. 2. Quantitative analyses of histologically identifiable gastric mucosal epithelial neutral glycoproteins and gastric adherent mucus from oxyntic and pyloric gland areas, and components of non-dialysable mucosubstances in gastric secretion were made under stress of pyloric obstruction for 4, 8, and 16 h durations. Epithelial mucin was identified by periodic acid-Schiff (PAS) staining technique and assessed from the ratio of gastric mucosal thickness to the depth of PAS positive materials in it. The remaining visible mucus adhered to the gastric mucosa was estimated by Alcian blue binding technique. The results were compared with that of identical control groups. 3. A significant reduction in mucosal epithelial PAS positive materials after 8 or 16 h of pylorus ligation was observed. 4. The Alcian blue binding capacity of the pyloric gland area was increased significantly after 4 h of pylorus ligation, while after 8 or 16 h it was reduced in both oxyntic and pyloric gland areas. 5. Significant reductions in the rate of gastric secretion and volume, as well as concentration of the components of non-dialysable mucosubstances, were observed, indicating decreased synthesis of mucus glycoproteins. 6. Disruption of the mucosal barrier may have occurred due to decreased mucus synthesis and acid-pepsin accumulation; both could be due to stress associated with gastric distension. 7. The present findings confirm the role of mucus in protecting the underlying gastric epithelium during stress. The adherent mucus offers a first line of defence and epithelial mucus a second line of defence.
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Affiliation(s)
- K Somasundaram
- Department of Physiology, Government Medical College, Surat, India
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34
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Abstract
Incorporation of L-[U-14C]leucine and of D[U-14C]glucose into proteins of fresh human gastric mucosa in vitro was studied after incubation of homogenized tissue and of intact mucosal pieces. CsCl centrifugation was used to separate high-density mucus glycoproteins from other mucosal proteins, and the macromolecular nature of radioactive mucosal glycoprotein fractions was confirmed by SDS/polyacrylamide-gel electrophoresis and autoradiography of the polyacrylamide gels. In all experiments a substantial proportion of total incorporated radioactivity was associated with gastric-mucosal glycoprotein fractions (CsCl fraction L3), indicating their biosynthesis. Radioactivity of these fractions was shown to co-chromatograph with carbohydrates when fractionated either directly or after reduction and alkylation (1) Sephadex G-200 chromatography in the excluded fractions and (2) by DEAE-cellulose ion-exchange chromatography. On incubation of intact mucosa, the major portion of radioactivity associated with the glycoprotein fractions of both leucine- and glucose-labelled specimens was secreted into the mucosal media during the course of the experiment. It is suggested that biosynthesis of mucus in vivo by gastric mucosa may be associated with rapid secretion of the synthesized macromolecules into the lumen of the stomach and that investigations of the metabolic processes within the mucosa should consider the products of secretion of the tissue. Incorporation of L-[U-14C]leucine implies biosynthesis of the polypeptide components of the macromolecules.
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35
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Cucala M, Bauerfeind P, Emde C, Gonvers JJ, Koelz HR, Blum AL. It is wise to prescribe NSAIDs with modern gastroprotective agents? Scand J Rheumatol Suppl 1987; 65:141-54. [PMID: 3317804 DOI: 10.3109/03009748709102193] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
The administration of non-steroidal anti-inflammatory drugs (NSAIDs) leads to mucosal lesions in the upper gastrointestinal tract. Furthermore, NSAIDs increase the risk of ulcer bleeding and perforation, but the overall risk of fatal complications is relatively small (about 21 per one million prescriptions). Therefore, in asymptomatic patients, it is not justified to prescribe NSAIDs together with gastroprotective agents. The following recommendations can be given with respect to the management of peptic lesions in patients taking NSAIDs: (i) Fibre endoscopy should be performed even when there are relatively mild symptoms since mucosal lesions in rheumatic patients under NSAIDs produce minor or no symptoms. (ii) "Modern" NSAIDs might produce less gastric lesions than aspirin. (iii) Rheumatic patients with peptic disorders should be treated with an H2-antagonist. (iv) After complications such as ulcer bleeding or after rapid recurrence of peptic lesions, maintenance treatment with an H2-antagonist is advisable.
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Affiliation(s)
- M Cucala
- Division de Gastro-entérologie, CHUV, Lausanne, Switzerland
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36
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37
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Hawkey CJ, Rampton DS. Prostaglandins and the gastrointestinal mucosa: are they important in its function, disease, or treatment? Gastroenterology 1985; 89:1162-88. [PMID: 3930341 DOI: 10.1016/0016-5085(85)90225-2] [Citation(s) in RCA: 251] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
In 1971 interest in the role of prostaglandins in the gastrointestinal tract was stimulated by the publication of two hypotheses--that aspirin damaged the gastric mucosa by inhibiting prostaglandin synthesis (1) and that cholera toxin caused diarrhea by stimulating it (2). Subsequent research into the gastrointestinal actions of prostaglandins has been considerable and now impinges on clinical practice. This paper reviews the involvement of prostaglandins and related compounds in mucosal protection, in ulcer healing, in diarrhea, and in gastrointestinal inflammation, with particular reference to the growing body of human data.
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38
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Shea-Donohue T, Danquechin-Dorval E, Montcalm E, El-Bayar H, Durakovic A, Conklin JJ, Dubois A. Alterations in gastric mucus secretion in rhesus monkeys after exposure to ionizing radiation. Gastroenterology 1985; 88:685-90. [PMID: 3881307 DOI: 10.1016/0016-5085(85)90138-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
The aim of the present study was to evaluate the effect of gamma-irradiation on soluble gastric mucus. Six conscious chair-adapted rhesus monkeys were studied once before and twice after exposure to ionizing irradiation (800 rads). Using a marker (99mTc-DTPA) dilution technique, acidic glycoprotein (AG), neutral glycoprotein (NG), ion, and fluid output were determined during a basal period and after the administration of an 80-ml water load. Irradiation significantly increased the outputs of both AG and NG during the basal period. After the water load, NG output remained elevated but irradiation abolished postload AG output thus inhibiting the normal rise in AG output stimulated by the load. Two days after irradiation NG output had returned to control levels whereas AG output was still suppressed. Sodium and potassium ion outputs were unaltered by irradiation. Chloride and fluid outputs were significantly inhibited on the day of irradiation but had returned to control levels within 3 days. These results indicate that irradiation produces significant changes in both the quantity and nature of the soluble mucus glycoproteins secreted into the gastric juice. It is suggested that these changes may compromise the protective ability of gastric mucus.
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39
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Turnberg LA. Gastric mucosal defence mechanisms. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. SUPPLEMENT 1985; 110:37-40. [PMID: 3895393 DOI: 10.3109/00365528509095829] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Gastric mucosa has a particular ability to resist acid/peptic digestion. The nature of the presumed barrier to acid and pepsin has been elusive but recent work suggests that a combination of mechanisms is likely to be involved. Amongst these the mucus gel layer combined with secretion of alkali by the surface epithelium is likely to form a first line defence. The demonstration of a pH gradient within the mucus gel layer supports such a hypothesis. Agents which damage the mucosa such as aspirin and bile salts inhibit the maintenance of the pH gradient allowing the luminal surface of the epithelium to become more acid. Prostaglandins enhance this pH gradient, an observation which may be relevant to the protective properties of prostaglandins. This alkaline zone can be compromised by high levels of luminal acidity and it thus has a limited capacity to prevent acid reaching the mucosa. The local microcirculation is of importance in maintaining surface epithelial metabolic integrity and interstitial fluid bicarbonate may be important in neutralising any acid which may reach the subepithelial layers. This may in part explain the ability of an actively secreting gastric epithelium to resist damage to a greater extent than a resting mucosa. Recent exciting work has focussed on the ability of gastric epithelium to reform by a process which has been termed restitution, after acute mucosal damage. This process appears to be rapid and occurs within an hour or so. Repeated rapid repair may be a common occurrence in the maintenance of mucosal integrity. Finally, it has been proposed that a hydrophobic property of surface epithelium in the stomach may be relevant to mucosal protection.
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Ohara S, Hotta K. Effects of fasting on mucus glycoprotein biosynthesis in rat stomach. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY. B, COMPARATIVE BIOCHEMISTRY 1985; 82:207-10. [PMID: 4053580 DOI: 10.1016/0305-0491(85)90227-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Biosynthetic activity of gastrin mucus glycoprotein in rats after fasting for 24 and 72 hr was studied by the organ culture technique. Fasting produced a slight reduction in gastric mucus glycoprotein biosynthesis in the corpus and antrum (about 70-90% of fed rats). Sulfation of gastric mucus glycoprotein was restrained in the corpus (18% in control for 72 hr).
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Gottfried S, Vine RS, Wan BY. A quantitative morphological study of the effects of carbenoxolone sodium on duodenal goblet-cells of the rat. GENERAL PHARMACOLOGY 1985; 16:297-8. [PMID: 4018547 DOI: 10.1016/0306-3623(85)90089-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
A direct microscopic and microdensitometric examination was carried out on duodenal goblet-cells of non-fasted and fasted rats with and without carbenoxolone sodium treatment. The results of microdensitometric examination revealed a marked and significant increase of mucus production in the non-fasted and fasted rats pretreated for 2 hr with a single oral dose of carbenoxolone sodium at 100 mg/kg. Fasting alone also increased mucus production. On microscopic examination, the number of duodenal goblet-cells full of mucosubstances in the non-fasted and fasted rats receiving carbenoxolone sodium treatment was approximately 20% higher than in the controls.
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Suwa T, Nakazima M, Shinozaki A, Kyogoku K, Mori Y. Cytoprotective effect of SU-88, an anti-ulcer agent, in the rat. JAPANESE JOURNAL OF PHARMACOLOGY 1984; 35:47-53. [PMID: 6590906 DOI: 10.1254/jjp.35.47] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
The gastric cytoprotective action of SU-88, an anti-ulcer agent, was studied in rats. SU-88 dose-dependently prevented the formation of gastric lesions induced by absolute ethanol as observed by PGE2. The efficacy of SU-88 when given i.p. was more potent than the p.o. administration. Indomethacin (5mg/kg, p.o.) given 30 min prior to SU-88 dosing blocked this protective effect, whereas it was not affected when indomethacin was given 30 min after the SU-88 dosing. Cimetidine, on the other hand, failed to exert a protective effect against the ethanol-induced lesions and caused a significant increase in the lesions induced by 0.6N HCI. Pretreatment with SU-88 prior to cimetidine resulted in a marked reduction in the lesions. SU-88 was found to increase the synthesis of gastric glycoproteins and to prevent the reduction of glycoprotein synthesis caused by the administration of absolute ethanol. However, no increase in the synthesis was observed 5 min after the SU-88 dosing, although the lesion was significantly suppressed at that time. These findings indicate that SU-88 possesses a cytoprotective effect and that this effect seems to be mediated by the increase in endogenous PG.
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Shorr LD, Sirinek KR, Page CP, Levine BA. The role of glucose in preventing stress gastric mucosal injury. J Surg Res 1984; 36:384-8. [PMID: 6546772 DOI: 10.1016/0022-4804(84)90115-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
UNLABELLED Reports from other investigators have shown the ability of pretreatment with either parenteral (glucose) or enteral (bolus Vivonex HN) nutrition to protect against stress ulcer formation, suggesting that the mechanism of protection may be substrate availability. However, these prior animal studies have used inordinately high amounts of Vivonex HN (equal to 1050 ml/hr in a human). This study compared cytoprotection afforded by pretreatment with a continuous infusion of Vivonex HN at a more clinically applicable level to that of both parenteral (ip) and enteral (po) glucose to test the above hypothesis. One hundred eight rats were infused (0.1 ml/min) for 30 min with: po water, ip water, po 25% glucose, ip 25% glucose, or po Vivonex HN. This was followed by 2 hr of cold-restraint stress. Serum glucose was determined. Poststress, animals were sacrificed, stomachs inspected, and mean ulcer index was calculated. Only oral 25% glucose offered significant gastric cytoprotection. Serum glucose was highest in both glucose groups. CONCLUSIONS (1) Vivonex HN pretreatment failed to cytoprotect in this model, (2) gastric cytoprotection by oral but not by parenteral glucose in the presence of similar serum glucose levels suggests that luminal factors, in addition to substrate availability, are necessary for this protection to occur.
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Murakami S, Mori Y. Changes in the Incorporating Activity of 35S-Sulfate into Gastric Sulfated Glycoproteins in the Rat with Erosions by Restraint and Water Immersion Stress. ACTA ACUST UNITED AC 1984; 35:279-86. [PMID: 6541264 DOI: 10.1254/jjp.35.279] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
The synthetic activity of rat gastric sulfated glycoproteins (SGP) in vitro was investigated at various time intervals after water immersion stress using 35S-sulfate as a precursor. More than 90 percent of the total radioactivity was incorporated into mucosal SGP, and the rest was incorporated into glycosaminoglycans in the gastric muscular layer. The incorporation of 35S-sulfate into SGP increased at 2 hr and decreased at 6 hr after the onset of stress. The incorporating activity again increased markedly at 12 hr and then recovered to the normal level at 24 hr after the onset of stress. An anti-ulcer agent, N-(N-acetyl-beta-alanyl)-L-histidine aluminum complex (AAHA), significantly increased the SGP synthetic activity at 12 hr and at 24 hr after the onset of stress. It was indicated from the elution patterns on the DEAE-cellulose column that AAHA increased the amount of highly sulfated glycoproteins compared with the stress control at 12 hr after the onset of stress. The uronic acid content in the gastric muscular layer of the rat was unchanged with stress. These results in the in vitro experiment indicate that the SGP synthetic activity does not decrease with stress load, but rather increases at 2 hr and at 12 hr after the onset of stress when a sufficient amount of 35S-sulfate is supplied. Accordingly, it is suggested that SGP facilitates the restoration of the gastric mucosal damage caused by stress.
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Ohara S, Kakei M, Ishihara K, Katsuyama T, Hotta K. Effects of fasting on mucus glycoprotein in rat stomach. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY. B, COMPARATIVE BIOCHEMISTRY 1984; 79:325-9. [PMID: 6210177 DOI: 10.1016/0305-0491(84)90383-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Quantitative changes and chemical composition of gastric mucus glycoproteins in rats after fasting for 24 and 72 hr were studied. The amount of glycoproteins increased in the corpus mucosa during these periods (220% in control for 72 hr), but remained the same in the antrum. The acidity of corpus glycoproteins decreased during the fasting.
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Ross IN, Turnberg LA. Studies of the 'mucus-bicarbonate' barrier on rat fundic mucosa: the effects of luminal pH and a stable prostaglandin analogue. Gut 1983; 24:1030-3. [PMID: 6629112 PMCID: PMC1420124 DOI: 10.1136/gut.24.11.1030] [Citation(s) in RCA: 29] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Gastric mucosa may protect itself from acid peptic digestion by maintaining an alkaline barrier zone within the layer of mucus coating its surface. We have measured the pH gradient in the mucous layer in vivo, on the gastric mucosa of anaesthetised rats using antimony chloride micro pH electrodes. The maximum pH recordable adjacent to the epithelium was 7.43 +/- 0.56 (n = 8) when the luminal bathing solution pH was 2. Adjusting the luminal pH to 7.0 caused the maximal pH to rise to 7.88 (range 7.59 to 8.08), a value which is significantly higher than either luminal or reported intraepithelial pH and suggests that active secretion of alkali is involved. Pretreatment with 16-16-dimethyl prostaglandin E2 (20 micrograms subcutaneously) significantly increased the maximal intramucus pH to 7.89 +/- 0.45 (n = 8) when luminal pH was 2 and prevented the fall in intramucus pH induced by luminal aspirin (20 mM). It did not prevent falls in pH provoked by the mucolytic agent n-acetyl cysteine or by a high luminal activity (pH 1.4). These data indicate that an alkaline environment is maintained adjacent to gastric mucosa and that while this is enhanced by prostaglandin it may be compromised by high luminal acid concentrations or by removal of the support provided by mucus. These observations may be relevant to the mechanisms of gastric mucosal protection against acid peptic damage.
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Curtis CG, Powell GM, Bradbury A, Rhodes C. The fate of fenclozic acid in the gut and its effect on some aspects of gut metabolism. Xenobiotica 1983; 13:483-96. [PMID: 6689100 DOI: 10.3109/00498258309052288] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
In the rat [14C]fenclozic acid is not metabolized in the gut and passes into the portal blood unchanged. After intraduodenal administration of [14C]fenclozic acid, a small proportion of the dose binds to high molecular weight substances in the gut wall. The incorporation of L-[U-14C]leucine and N-[3H]acetyl-D-glucosamine into acid-precipitable materials by isolated mucosal cells and homogenates of gut mucosal cells was inhibited by fenclozic acid in a dose-dependent manner. Other non-steroidal anti-inflammatory drugs (indomethacin, phenylbutazone, prednisolone, salicylic acid and paracetamol) were tested for their potency as inhibitors of glycoprotein production by whole cell preparations and by homogenized gut cell preparations. Marked differences were observed in the inhibitory potency of indomethacin, paracetamol and salicylic acid in the two experimental systems. Fenclozic acid had no major effect on the rate of total glycoprotein production by the isolated perfused rat liver or by the duodenal mucosa in situ. Fenclozic acid displaces albumin-bound [3H]tryptophan and increases the level of hepatic tryptophan pyrrolase approx. threefold. The inhibition of gut glycoprotein production by fenclozic acid was not prevented by free tryptophan.
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Emmanouilidis A, Nicolopoulou-Stamati P, Manousos O. Effects of therapeutic doses of cimetidine and oxmetidine on the parietal cell population, gastric mucosal glycoproteins and surface gastric epithelium, in duodenal ulcer patients. J Int Med Res 1982; 10:113-7. [PMID: 7067921 DOI: 10.1177/030006058201000208] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
The histamine H2-receptor antagonists cimetidine and oxmetidine were administered in a dose of 1 g/day for 4 weeks to fifteen duodenal ulcer patients. Their effects on the parietal cell population, the intracellular mucosal glycoproteins and the surface gastric epithelium were investigated by comparing pre- and post-treatment fundic biopsies. It was found that treatment with either agent had no effect on any of the assessments made.
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