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Dinetz E, Zeballos-Palacios C, Martinez CA. Addressing the Missing Links in Cardiovascular Aging. Clin Interv Aging 2024; 19:873-882. [PMID: 38774249 PMCID: PMC11107914 DOI: 10.2147/cia.s457180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 04/27/2024] [Indexed: 05/24/2024] Open
Abstract
The aim of this manuscript is to provide a review of available options to enhance cardiovascular health and prevent cardiovascular disease (CVD) in the aging population using a systems-biology approach. These include the role of the gut microbiome, the early identification and removal of environmental toxins, and finally age related sex hormones and supplement replacement which all influence aging. Implementing such a comprehensive approach has the potential to facilitate earlier risk assessment, disease prevention, and even improve mortality. Further study in these areas will continue to advance our understanding and refine therapeutic interventions for a healthier cardiovascular aging process.
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Affiliation(s)
- Elliot Dinetz
- Department of Integrative and Family Medicine, University of Miami Miller School of Medicine Miami, Miami, FL, USA
| | | | - Claudia A Martinez
- Department of Medicine, Cardiovascular Division, University of Miami Miller School of Medicine, Miami, FL, USA
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2
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Yulizal OK, Lelo A, Ilyas S, Kusumawati RL. The effect of Channa striata extract and standard eradication regimen on asymmetric dimethylarginine in Helicobacter pylori gastritis rat model. Vet World 2020; 13:1605-1612. [PMID: 33061234 PMCID: PMC7522937 DOI: 10.14202/vetworld.2020.1605-1612] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 06/24/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND AIM The presence of gastric mucosa or submucosa inflammation due to Helicobacter pylori leads to histological changes. Gastric injury, pro-inflammatory factors, and oxidative stress in H. pylori infection produce asymmetric dimethylarginine (ADMA), which are a competitive inhibitor of nitric oxide synthase. Investigations were carried out aimed at finding new drugs derived from natural products for the treatment of H. pylori. Channa striata is known to have in vitro anti-inflammatory and antimicrobial properties. This study aimed to investigate the effect of C. striata extract and a standard eradication regimen on ADMA levels and histological changes in the H. pylori gastritis rat model. MATERIALS AND METHODS Thirty-five male rats were randomly and equally divided into five groups. Group-1 was the negative control group and Groups-2 to 5 were H. pylori-infected groups. Groups-3 to 5 were administered C. striata extract, a standard eradication regimen, and a combination of standard eradication regimen and C. striata extract, respectively. Histological examination and serum ADMA levels were analyzed. The difference between groups was analyzed using the Kruskal-Wallis and one-way analysis of variance tests. The significance was p<0.05. RESULTS Serum ADMA levels and severity of gastritis were higher in infected groups compared to the negative control group (p<0.05). The severity of gastritis and mean ADMA levels in the group that received a single administration of the C. striata extract was higher than the others (p<0.05). Serum ADMA levels and severity of gastritis were significantly reduced in the group that received a combination of standard eradication regimen and C. striata extract (p<0.05). CONCLUSION Single administration of C. striata extract worsens the severity of gastritis and increased serum ADMA levels in the H. pylori gastritis rat model. The administration of a combination of standard eradication regimen and C. striata extract reduces serum ADMA levels and significantly improves the severity of H. pylori gastritis rat model.
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Affiliation(s)
- OK Yulizal
- Department of Internal Medicine, Faculty of Medicine, Universitas Prima Indonesia, Medan, Indonesia
- School of Medicine, Universitas Sumatera Utara, Medan, Indonesia
| | - Aznan Lelo
- Department of Pharmacology and Therapeutics, School of Medicine, Universitas Sumatera Utara, Medan, Indonesia
| | - Syafruddin Ilyas
- Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan, Indonesia
| | - Raden Lia Kusumawati
- Department of Microbiology, School of Medicine, Universitas Sumatera Utara, H. Adam Malik General Hospital, Medan, Indonesia
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Zhao DQ, Xue H, Sun HJ. Nervous mechanisms of restraint water-immersion stress-induced gastric mucosal lesion. World J Gastroenterol 2020; 26:2533-2549. [PMID: 32523309 PMCID: PMC7265141 DOI: 10.3748/wjg.v26.i20.2533] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 04/07/2020] [Accepted: 04/28/2020] [Indexed: 02/06/2023] Open
Abstract
Stress-induced gastric mucosal lesion (SGML) is one of the most common visceral complications after trauma. Exploring the nervous mechanisms of SGML has become a research hotspot. Restraint water-immersion stress (RWIS) can induce GML and has been widely used to elucidate the nervous mechanisms of SGML. It is believed that RWIS-induced GML is mainly caused by the enhanced activity of vagal parasympathetic nerves. Many central nuclei, such as the dorsal motor nucleus of the vagus, nucleus of the solitary tract, supraoptic nucleus and paraventricular nucleus of the hypothalamus, mediodorsal nucleus of the thalamus, central nucleus of the amygdala and medial prefrontal cortex, are involved in the formation of SGML in varying degrees. Neurotransmitters/neuromodulators, such as nitric oxide, hydrogen sulfide, vasoactive intestinal peptide, calcitonin gene-related peptide, substance P, enkephalin, 5-hydroxytryptamine, acetylcholine, catecholamine, glutamate, γ-aminobutyric acid, oxytocin and arginine vasopressin, can participate in the regulation of stress. However, inconsistent and even contradictory results have been obtained regarding the actual roles of each nucleus in the nervous mechanism of RWIS-induced GML, such as the involvement of different nuclei with the time of RWIS, the different levels of involvement of the sub-regions of the same nucleus, and the diverse signalling molecules, remain to be further elucidated.
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Affiliation(s)
- Dong-Qin Zhao
- Key Laboratory of Animal Resistance of Shandong Province, College of Life Sciences, Shandong Normal University, Jinan 250014, Shandong Province, China
| | - Hua Xue
- Key Laboratory of Animal Resistance of Shandong Province, College of Life Sciences, Shandong Normal University, Jinan 250014, Shandong Province, China
| | - Hai-Ji Sun
- Key Laboratory of Animal Resistance of Shandong Province, College of Life Sciences, Shandong Normal University, Jinan 250014, Shandong Province, China
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Yang J, Zhou W, Gu Y, Dai J, Li X, Tai P, Li Y, Ma X, Zhang Y. Protective effect of Pu-erh tea extracts against ethanol-induced gastric mucosal damage in rats. Biomed Rep 2018; 8:335-342. [PMID: 29556381 PMCID: PMC5844118 DOI: 10.3892/br.2018.1068] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 02/02/2018] [Indexed: 12/17/2022] Open
Abstract
Pu-erh tea has become a focus of research due to its reported biological activities, including anti-oxidation, anti-inflammation and anti-immunosenescence. The present study was performed to evaluate the potential gastroprotective function of Pu-erh tea extracts against ethanol-induced gastric mucosal damage in rats. Sprague Dawley rats were randomly divided into seven groups: A normal control, a model control, a cimetidine (0.08 g/kg) group, three Pu-erh tea extracts groups (low, moderate and high-dose; 0.50, 1.00 and 1.50 g/kg, respectively, and a green tea powder (1.00 g/kg) group. The normal and model groups were pre-treated with distilled water while the other groups were respectively administered cimetidine, Pu-erh tea extracts and green tea powder for 14 days. Then, absolute ethanol was orally administered to the rats of all groups excluding the normal controls. The effects of the pretreatments on gastric mucosal injury were evaluated by gross assessment of gastric lesions, examination of histopathology and determination of myeloperoxidase (MPO) activity and asymmetric arginine (ADMA) concentration in gastric mucosal homogenate. Pre-treatment with cimetidine or Pu-erh tea extracts markedly suppressed the formation of ethanol-induced gastric lesions. Furthermore, clear decreases in MPO activity and ADMA concentration in the gastric mucosal homogenate were observed following pretreatment with cimetidine or Pu-erh tea extracts. The anti-gastric ulcer activity of green tea was less than that of Pu-erh tea. Overall, these effects of Pu-erh tea extracts may be due to potential functions in protecting the gastric mucus layer and suppressing inflammation.
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Affiliation(s)
- Jinna Yang
- Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China
| | - Wangyi Zhou
- Department of Pharmacology, Tasly R&D Institute, Tasly Pharmaceuticals, Inc., Tianjin 300410, P.R. China
| | - Yaru Gu
- Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China
| | - Jinwei Dai
- Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China
| | - Xinxin Li
- Department of Pharmacology, Tasly R&D Institute, Tasly Pharmaceuticals, Inc., Tianjin 300410, P.R. China
| | - Ping Tai
- Department of Pharmacology, Tasly R&D Institute, Tasly Pharmaceuticals, Inc., Tianjin 300410, P.R. China
| | - Yanchuan Li
- Department of Pharmacology, Tasly R&D Institute, Tasly Pharmaceuticals, Inc., Tianjin 300410, P.R. China
| | - Xiaohui Ma
- Department of Pharmacology, Tasly R&D Institute, Tasly Pharmaceuticals, Inc., Tianjin 300410, P.R. China
| | - Yuyang Zhang
- Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China
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Gastroprotective Mechanism and Ulcer Resolution Effect of Cyrtocarpa procera Methanolic Extract on Ethanol-Induced Gastric Injury. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:2862706. [PMID: 29507589 PMCID: PMC5817374 DOI: 10.1155/2018/2862706] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Accepted: 11/29/2017] [Indexed: 12/30/2022]
Abstract
Gastric ulcers are a worldwide health problem and their poor healing is one of the most important causes for their recurrence. We have previously reported the remarkable gastroprotective and anti-Helicobacter pylori activities of the methanolic extract (CpMet) of Cyrtocarpa procera bark. This work investigates, in a murine model, the CpMet gastroprotective mechanism and establishes its preclinical efficacy in the resolution of ethanol-induced gastric ulcers. The results showed that the gastroprotective activity of CpMet is mainly associated with endogenous NO and prostaglandins, followed by sulfhydryl groups and KATP channels. Furthermore, CpMet (300 mg/kg, twice a day) orally administered during 20 consecutive days promoted an ulcer area reduction of 62.65% at the 20th day of the treatment. The effect was confirmed macroscopically by the alleviation of gastric mucosal erosions and microscopically by an increase in mucin content and a reduction in the inflammatory infiltration at the site of the ulcer. No clinical symptoms or signs of toxicity were observed in the treated animals. The results indicate the safety and efficacy of CpMet in promoting high quality of ulcer healing by different mechanisms, but mostly through cytoprotective and anti-inflammatory effects, making it a promising phytodrug for ulcer treatment.
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Mukherjee K, Kavalukas SL, Barbul A. Nutritional Aspects of Gastrointestinal Wound Healing. Adv Wound Care (New Rochelle) 2016; 5:507-515. [PMID: 27867755 DOI: 10.1089/wound.2015.0671] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 09/23/2015] [Indexed: 02/07/2023] Open
Abstract
Significance: Although the wound healing cascade is similar in many tissues, in the gastrointestinal tract mucosal healing is critical for processes such as inflammatory bowel disease and ulcers and healing of the mucosa, submucosa, and serosal layers is needed for surgical anastomoses and for enterocutaneous fistula. Failure of wound healing can result in complications including infection, prolonged hospitalization, critical illness, organ failure, readmission, new or worsening enterocutaneous fistula, and even death. Recent Advances: Recent advances are relevant for the role of specific micronutrients, such as vitamin D, trace elements, and the interplay between molecules with pro- and antioxidant properties. Our understanding of the role of other small molecules, genes, proteins, and macronutrients is also rapidly changing. Recent work has elucidated relationships between oxidative stress, nutritional supplementation, and glucose metabolism. Thresholds have also been established to define adequate preoperative nutritional status. Critical Issues: Further work is needed to establish standards and definitions for measuring the extent of wound healing, particularly for inflammatory bowel disease and ulcers. In addition, a mounting body of evidence has determined the need for adequate preoperative nutritional supplementation for elective surgical procedures. Future Directions: A large portion of current work is restricted to model systems in rodents. Therefore, additional clinical and translational research is needed in this area to promote gastrointestinal wound healing in humans, particularly those suffering from critical illness, patients with enterocutaneous fistula, inflammatory bowel disease, and ulcers, and those undergoing surgical procedures.
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Affiliation(s)
- Kaushik Mukherjee
- Division of Trauma and Surgical Critical Care, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Sandra L. Kavalukas
- Department of General Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Adrian Barbul
- Department of General Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
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İlhan N, Ateş K, İlhan N, Kaman D, Çeliker H. eNOS Glu298Asp Polymorphism and Endothelial Dysfunction in Patients with and without End-stage Renal Disease. Balkan Med J 2016; 33:128-37. [PMID: 27403380 DOI: 10.5152/balkanmedj.2016.16566] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Accepted: 10/20/2015] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Chronic kidney diseases are known to influence nitric oxide metabolites (NOx) and asymmetric dimethylarginine (ADMA), though the exact mechanism is still poorly understood. AIMS The purpose of the present study was to examine eNOS Glu298Asp gene polymorphism, plasma NOx and ADMA concentration in subjects with and without End-stage Renal Disease. STUDY DESIGN Case-control study. METHODS In this study, genotype distributions of Glu-298Asp in exon 7 of the eNOS gene polymorphisms in 130 hemodialysis and 64 peritoneal dialysis patients were compared with 92 controls. NOx was measured by using the Griess reaction while arginine, ADMA and SDMA measurements were performed by HPLC. Genotyping for eNOS Glu298Asp polymorphism was detected with the polymerase chain reaction and/or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS When the genotype frequencies of TT and GT genes were compared between both groups, there was no detected statistically important difference, even-though a TT genotype frequency was 27 (20.8%) versus 17 (26.6%), GT heterozygote genotype frequency was 52 (40%) versus 22 (34.4%), and GG homozygote genotype frequency was 51 (39.2%) versus 25 (39.1%), respectively (p>0.05). NOx, SDMA and ADMA concentrations were significantly elevated in subjects with hemodialysis patients as compared to their corresponding controls. Whereas nitrite was found to be significantly decreased in the patient with peritoneal dialysis. CONCLUSION Not observed any connection between the Glu298Asp polymorphism in the eNOS gene and end-stage Renal Diseases in our study population under different dialysis treatments. However, higher ADMA and SDMA concentrations in subjects with ESRD support the existing hypothesis that NOx overproduction affects endothelial dysfunction. Thus, the reduction of ADMA and SDMA concentrations might play a protective role in ESRD patients.
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Affiliation(s)
- Nevin İlhan
- Department of Medical Biochemistry, Fırat University School of Medicine, Elazığ, Turkey
| | - Kadir Ateş
- Department of Medical Biochemistry, Fırat University School of Medicine, Elazığ, Turkey
| | - Necip İlhan
- Department of Medical Biochemistry, Fırat University School of Medicine, Elazığ, Turkey
| | - Dilara Kaman
- Department of Medical Biochemistry, Fırat University School of Medicine, Elazığ, Turkey
| | - Hüseyin Çeliker
- Department of Nephrology, Fırat University Hospital, Elazığ, Turkey
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Ahluwalia A, Gladwin M, Coleman GD, Hord N, Howard G, Kim-Shapiro DB, Lajous M, Larsen FJ, Lefer DJ, McClure LA, Nolan BT, Pluta R, Schechter A, Wang CY, Ward MH, Harman JL. Dietary Nitrate and the Epidemiology of Cardiovascular Disease: Report From a National Heart, Lung, and Blood Institute Workshop. J Am Heart Assoc 2016; 5:e003402. [PMID: 27385425 PMCID: PMC5015377 DOI: 10.1161/jaha.116.003402] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Amrita Ahluwalia
- The William Harvey Research Institute, Barts & The London Medical School, Queen Mary University of London, UK
| | - Mark Gladwin
- Vascular Medicine Institute, Pittsburgh University, Pittsburgh, PA
| | | | | | | | | | - Martin Lajous
- Nacional de Salud Pública de Mexico, Mexico, Albania
| | | | - David J Lefer
- Louisiana State University Health Sciences Center, New Orleans, LA
| | - Leslie A McClure
- Dornsife School of Public Health at Drexel University, Philadelphia, PA
| | | | - Ryszard Pluta
- National Institute of Neurological Disorders and Stroke, Bethesda, MD
| | - Alan Schechter
- National Institute for Diabetes and Digestive and Kidney Diseases, Bethesda, MD
| | - Chia-Yih Wang
- National Center for Health Statistics, CDC, Hyattsville, MD
| | | | - Jane L Harman
- Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD
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Zhang H, Ding C, Suo Z, Kang Y. Effect of Helicobacter pylori on cyclooxygenase-2 and inducible nitric oxide synthase in patients with gastric precancerous lesions and its clinical significance. Exp Ther Med 2015; 9:2364-2368. [PMID: 26136988 DOI: 10.3892/etm.2015.2387] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Accepted: 02/16/2015] [Indexed: 02/06/2023] Open
Abstract
The aim of this study was to investigate the effect of Helicobacter pylori (Hp) on cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) levels in patients with gastric precancerous lesions and its clinical significance. A total of 114 patients with gastric precancerous lesions, 57 whom were positive for Hp (observation group) and 57 of whom were negative for Hp (control group), were selected for the study. The mRNA levels of COX-2 and iNOS in the gastric precancerous lesion tissue from the two groups of patients were analyzed through the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein expression levels of COX-2 and iNOS were analyzed using western blotting and an iNOS kit, respectively. In addition, normal human gastric mucosal GES-1 cells were cultured in vitro and stimulated by Hp for 3, 6, 9 and 12 h. The variations in the mRNA and protein levels of COX-2 and iNOS were then analyzed via RT-qPCR and western blotting. Compared with the control group, the mRNA levels of COX-2 and iNOS in the gastric tissue from the observation group were significantly increased (P<0.05). Furthermore, the expression level of COX-2 and iNOS protein in the gastric tissue from the observation group was significantly higher than that in the tissue from the control group (P<0.05). In vitro analysis showed that the COX-2 and iNOS mRNA and protein levels were significantly increased in the Hp-stimulated normal human gastric mucosal GES-1 cells compared with those in the unstimulated cells. Furthermore, the effect was time-dependent (P<0.05). In conclusion, COX-2 and iNOS are the main inflammatory markers. Hp can induce high expression levels of COX-2 and iNOS in gastric precancerous lesion tissue, which may be associated with the occurrence and development of gastric precancerous lesions.
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Affiliation(s)
- Hui Zhang
- Department of Digestive Medicine, Henan University Huaihe Hospital, Kaifeng, Henan 475000, P.R. China
| | - Chunsheng Ding
- Department of Digestive Medicine, Henan University Huaihe Hospital, Kaifeng, Henan 475000, P.R. China
| | - Zhimin Suo
- Department of Digestive Medicine, Henan University Huaihe Hospital, Kaifeng, Henan 475000, P.R. China
| | - Yuhua Kang
- Department of Digestive Medicine, Henan University Huaihe Hospital, Kaifeng, Henan 475000, P.R. China
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Magierowski M, Jasnos K, Sliwowski Z, Surmiak M, Krzysiek-Maczka G, Ptak-Belowska A, Kwiecien S, Brzozowski T. Exogenous asymmetric dimethylarginine (ADMA) in pathogenesis of ischemia-reperfusion-induced gastric lesions: interaction with protective nitric oxide (NO) and calcitonin gene-related peptide (CGRP). Int J Mol Sci 2014; 15:4946-4964. [PMID: 24658439 PMCID: PMC3975433 DOI: 10.3390/ijms15034946] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 03/03/2014] [Accepted: 03/04/2014] [Indexed: 12/26/2022] Open
Abstract
Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthesis inhibitor and pro-inflammatory factor. We investigated the role of ADMA in rat gastric mucosa compromised through 30 min of gastric ischemia (I) and 3 h of reperfusion (R). These I/R animals were pretreated with ADMA with or without the combination of L-arginine, calcitonin gene-related peptide (CGRP) or a small dose of capsaicin, all of which are known to afford protection against gastric lesions, or with a farnesoid X receptor (FXR) agonist, GW 4064, to increase the metabolism of ADMA. In the second series, ADMA was administered to capsaicin-denervated rats. The area of gastric damage was measured with planimetry, gastric blood flow (GBF) was determined by H2-gas clearance, and plasma ADMA and CGRP levels were determined using ELISA and RIA. ADMA significantly increased I/R-induced gastric injury while significantly decreasing GBF, the luminal NO content, and the plasma level of CGRP. This effect of ADMA was significantly attenuated by pretreatment with CGRP, L-arginine, capsaicin, or a PGE2 analogue. In GW4064 pretreated animals, the I/R injury was significantly reduced and this effect was abolished by co-treatment with ADMA. I/R damage potentiated by ADMA was exacerbated in capsaicin-denervated animals with a further reduction of CGRP. Plasma levels of IL-10 were significantly decreased while malonylodialdehyde (MDA) and plasma TNF-α contents were significantly increased by ADMA. In conclusion, ADMA aggravates I/R-induced gastric lesions due to a decrease of GBF, which is mediated by a fall in NO and CGRP release, and the enhancement of lipid peroxidation and its pro-inflammatory properties.
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Affiliation(s)
- Marcin Magierowski
- Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland.
| | - Katarzyna Jasnos
- Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland.
| | - Zbigniew Sliwowski
- Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland.
| | - Marcin Surmiak
- Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland.
| | - Gracjana Krzysiek-Maczka
- Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland
| | - Agata Ptak-Belowska
- Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland
| | - Slawomir Kwiecien
- Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland.
| | - Tomasz Brzozowski
- Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland.
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Franceschelli S, Ferrone A, Pesce M, Riccioni G, Speranza L. Biological functional relevance of asymmetric dimethylarginine (ADMA) in cardiovascular disease. Int J Mol Sci 2013; 14:24412-21. [PMID: 24351825 PMCID: PMC3876119 DOI: 10.3390/ijms141224412] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 12/05/2013] [Accepted: 12/06/2013] [Indexed: 12/20/2022] Open
Abstract
There is growing evidence that increased levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) may contribute to endothelial dysfunction. Studies in animal models as well as in humans have suggested that the increase in ADMA occurs at a time when vascular disease has not yet become clinically evident. ADMA competitively inhibits NO elaboration by displacing L-arginine from NO synthase. In a concentration-dependent manner, it thereby interferes not only with endothelium-dependent, NO-mediated vasodilation, but also with other biological functions exerted by NO. The upshot may be a pro-atherogenic state. Recently, several studies have investigated the effect of various therapeutical interventions on ADMA plasma concentrations.
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Affiliation(s)
- Sara Franceschelli
- Department of Medicine and Science of Aging, University G. D’Annunzio-Chieti, Chieti 66100, Italy; E-Mails: (S.F.); (A.F.); (M.P.)
| | - Alessio Ferrone
- Department of Medicine and Science of Aging, University G. D’Annunzio-Chieti, Chieti 66100, Italy; E-Mails: (S.F.); (A.F.); (M.P.)
| | - Mirko Pesce
- Department of Medicine and Science of Aging, University G. D’Annunzio-Chieti, Chieti 66100, Italy; E-Mails: (S.F.); (A.F.); (M.P.)
| | - Graziano Riccioni
- Intensive Cardiology Care Unit, San Camillo de Lellis Hospital, San Severo (FG) 71016, Italy; E-Mail:
| | - Lorenza Speranza
- Department of Medicine and Science of Aging, University G. D’Annunzio-Chieti, Chieti 66100, Italy; E-Mails: (S.F.); (A.F.); (M.P.)
- Author to whom correspondence should be addressed; E-Mail: ; Tel.: +39-871-355-4550; Fax: +39-871-355-4551
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12
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Sinha M, Gautam L, Shukla PK, Kaur P, Sharma S, Singh TP. Current perspectives in NSAID-induced gastropathy. Mediators Inflamm 2013; 2013:258209. [PMID: 23576851 PMCID: PMC3610380 DOI: 10.1155/2013/258209] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2012] [Accepted: 02/14/2013] [Indexed: 12/18/2022] Open
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection.
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Affiliation(s)
| | | | | | | | - Sujata Sharma
- Department of Biophysics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India
| | - Tej P. Singh
- Department of Biophysics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India
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