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Sarmento EB, Sassone LM, Pinto KP, Ferreira CMA, da Fidalgo TKS, Lopes RT, Alves ATNN, Freitas-Fernandes LB, Valente AP, Neves RH, da Silva EJNL. Evaluation of a potential bidirectional influence of metabolic syndrome and apical periodontitis: An animal-based study. Int Endod J 2025; 58:467-483. [PMID: 39797578 DOI: 10.1111/iej.14189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 11/24/2024] [Accepted: 12/23/2024] [Indexed: 01/13/2025]
Abstract
AIM This study aimed to explore the possible bidirectional interrelations between fructose-induced metabolic syndrome (MS) and apical periodontitis (AP). METHODOLOGY Twenty-eight male Wistar rats were distributed into four groups (n = 7, per group): Control (C), AP, Fructose Consumption (FRUT) and Fructose Consumption and AP (FRUT+AP). The rats in groups C and AP received filtered water, while those in groups FRUT and FRUT+AP received a 20% fructose solution mixed with water to induce MS. The groups AP and FRUT+AP had the pulp of their right mandibular first molar exposed to induce AP. Food consumption, murinometric measurements, blood glucose levels and glucose tolerance were monitored. Fifty-six days after the start of the experiment, the animals were euthanized, and serum samples were collected for metabolomic analysis. Mandibles, livers and right kidneys were also collected. The area and volume of the periapical lesions were calculated using micro-computed tomography. Histopathological evaluation was performed. Kruskal-Wallis followed by the Student-Newman-Keuls or Mann-Whitney tests and one-way anova followed by Tukey's or Independent t-test were used for non-parametric and parametric data, respectively (p < .05). Multivariate analysis and variable importance in projection score were applied to assess metabolite profile differences among groups (p < .05). RESULTS FRUT and FRUT+AP groups showed significantly increased fluid intake, body mass, abdominal circumference, blood glucose levels, liver weight and visceral fat weight (p < .05), indicating the development of MS. The analyses of the metabolite profile suggest increasing glucose, histidine, lactate, fatty acid and phenylalanine in the FRUT+AP group. There were no significant differences in volume and area of periapical lesions in micro-CT analyses (p = .1048 and p = .7494, respectively). Histopathological analysis of the hemimandibles demonstrated areas of inflammatory response, necrosis and microabscess in the periapical region. Hepatic histopathological observations indicated notable differences in cell appearance, with the FRUT and FRUT+AP groups showing signs of microsteatosis. Kidney analysis revealed Bowman's space dilation in the FRUT and AP groups, while the FRUT+AP group exhibited retracted Bowman's space, suggesting a possible alteration in renal filtration capacity. CONCLUSIONS MS had no impact on the progression of AP in rats. However, AP exacerbated the systemic state affected by MS, with changes in liver and kidney tissues and metabolite levels.
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Affiliation(s)
- Estéfano Borgo Sarmento
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Luciana Moura Sassone
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Karem Paula Pinto
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Cláudio Malizia Alves Ferreira
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Tatiana Kelly Silva da Fidalgo
- Department of Community and Preventive Dentistry, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Ricardo Tadeu Lopes
- Nuclear Engineering Program, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | | | - Liana Bastos Freitas-Fernandes
- National Center for Nuclear Magnetic Resonance, Medical Biochemistry, Rio de Janeiro Federal University, Rio de Janeiro, Brazil
| | - Ana Paula Valente
- National Center for Nuclear Magnetic Resonance, Medical Biochemistry, Rio de Janeiro Federal University, Rio de Janeiro, Brazil
| | - Renata Heisler Neves
- Romero Lascasas Porto Helminthology Laboratory, Department of Microbiology, Immunology and Parasitology, Medical Sciences College (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Emmanuel João Nogueira Leal da Silva
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
- Department of Endodontics, Grande Rio University (UNIGRANRIO), Rio de Janeiro, Brazil
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Huang Y, Yin C, Wang J, Wang M, Zheng X, Xie M, Wang J. Impact of Glutamine-Enhanced Parenteral Nutrition on Postoperative Outcomes in Colorectal Cancer Patients. Cancer Manag Res 2024; 16:1329-1344. [PMID: 39372706 PMCID: PMC11456277 DOI: 10.2147/cmar.s476648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 09/10/2024] [Indexed: 10/08/2024] Open
Abstract
Purpose This study investigated the effects of parenteral glutamine (Gln) supplement immunonutrition versus conventional nutritional support on postoperative Clavien-Dindo classification complications and recovery, perioperative nutritional status, and immune, inflammation, and safety indicators in patients with colorectal cancer (CRC). Patients and Methods Clinical data were collected for a retrospective cohort study of 178 patients (58 and 120 patients in the observation and control groups, respectively) who underwent radical resection of CRC from January 2019 to December 2021. The incidence of postoperative complications was calculated. Postoperative recovery, nutritional indicators, inflammatory factors indicator, and the safety indicators before operation and at 1, 3, and 7 days after operation were compared. SPSS 29.0 statistical software was used for statistical analysis. Results The incidence of postoperative overall complications in the control group and the observation group was 22.50% (27/120) and 17.24% (10/58), respectively, and there was no significant difference between the two groups (P=0.42). The incidence of postoperative complications of Clavien-Dindo grade ≥III in the control group and the observation group was 14.17% (17/120) and 3.45% (2/58), respectively, and the difference between the two groups was statistically significant (P=0.03). Secondary outcomes (first exhaust, defecation, and liquid diet intake times) were significantly recovered earlier in the observation group than those in the control group (P<0.05), while the postoperative hospital stay was significantly shorter(P=0.04). The perioperative nutritional status did not significantly differ between the groups before and after surgery(P>0.05), although significant differences were observed in several inflammatory and safety indicators(P<0.05). Conclusion Unlike conventional nutritional support, postoperative parenteral Gln supplementation reduced the incidence of postoperative Clavien-Dindo complications grade ≥III in patients with CRC while increasing intestinal and immune functions, decreasing inflammation, and reducing the length of hospital stay.
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Affiliation(s)
- Yong Huang
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China
| | - Chunmei Yin
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China
| | - Jue Wang
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China
| | - Maijian Wang
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China
| | - Xingbin Zheng
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China
| | - Ming Xie
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China
| | - Jiwei Wang
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China
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Wang C, Sun D, Deng Q, Sun L, Hu L, Fang Z, Zhao J, Gooneratne R. Elephantopus scaber L. Polysaccharides Alleviate Heat Stress-Induced Systemic Inflammation in Mice via Modulation of Characteristic Gut Microbiota and Metabolites. Nutrients 2024; 16:262. [PMID: 38257155 PMCID: PMC10819175 DOI: 10.3390/nu16020262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Revised: 01/07/2024] [Accepted: 01/12/2024] [Indexed: 01/24/2024] Open
Abstract
Elephantopus scaber L. (ESL) is a Chinese herb that is used both as a food and medicine, often being added to soups in summer in south China to relieve heat stress (HS), but its exact mechanism of action is unknown. In this study, heat-stressed mice were gavaged with ESL polysaccharides (ESLP) at 0, 150, 300, and 450 mg/kg/d-1 (n = 5) for seven days. The gut microbiota composition, short-chain fatty acids (SCFAs), seven neurotransmitters in faeces, expression of intestinal epithelial tight junction (TJ) proteins (Claudin-1, Occludin), and serum inflammatory cytokines were measured. The low dose of ESLP (ESLL) improved the adverse physiological conditions; significantly reduced the cytokines (TNF-α, IL-1β, IL-6) and lipopolysaccharide (LPS) levels (p < 0.05); upregulated the expression of Claudin-1; restored the gut microbiota composition including Achromobacter and Oscillospira, which were at similar levels to those in the normal control group; significantly increased beneficial SCFAs like butyric acid and 5-HT levels in the faeces of heat-stressed mice; and significantly decreased the valeric acid and glutamic acid level. The level of inflammatory markers significantly correlated with the above-mentioned indicators (p < 0.05). Thus, ESLL reduced the HS-induced systemic inflammation by optimizing gut microbiota (Achromobacter, Oscillospira) abundance, increasing gut beneficial SCFAs like butyric acid and 5-HT levels, and reducing gut valeric and glutamic acid levels.
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Affiliation(s)
- Chen Wang
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (C.W.); (D.S.); (L.S.); (L.H.); (Z.F.)
| | - Dongfang Sun
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (C.W.); (D.S.); (L.S.); (L.H.); (Z.F.)
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Qi Deng
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (C.W.); (D.S.); (L.S.); (L.H.); (Z.F.)
| | - Lijun Sun
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (C.W.); (D.S.); (L.S.); (L.H.); (Z.F.)
| | - Lianhua Hu
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (C.W.); (D.S.); (L.S.); (L.H.); (Z.F.)
| | - Zhijia Fang
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (C.W.); (D.S.); (L.S.); (L.H.); (Z.F.)
| | - Jian Zhao
- School of Chemical Engineering, The University of New South Wales, Sydney, NSW 2052, Australia;
| | - Ravi Gooneratne
- Department of Wine, Food and Molecular Biosciences, Faculty of Agriculture and Life Sciences, Lincoln University, P.O. Box 85084, Lincoln 7647, New Zealand;
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Al-Taie A, Al-Shohani AD, Albasry Z, Altaee A. Current topical trends and novel therapeutic approaches and delivery systems for oral mucositis management. JOURNAL OF PHARMACY AND BIOALLIED SCIENCES 2020; 12:94-101. [PMID: 32742107 PMCID: PMC7373116 DOI: 10.4103/jpbs.jpbs_198_19] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Revised: 11/21/2019] [Accepted: 12/01/2019] [Indexed: 11/12/2022] Open
Abstract
Oral mucositis (OM) is an extremely serious and challenging complication of chemoradiotherapy, which may limit the efficacy of cancer treatment. Complications related to OM include potential nutrition impairment, high economic burden, and negative impacts on patients' quality of life. Current therapeutic options with local traditional pharmaceutical formulations are largely focused on controlling symptoms, and only few agents are available for treatment. Several local supportive and palliative agents are used for the prevention of OM; however, a standard treatment for the disease has not been confirmed yet. The efficacy of treatment could be improved through the introduction of new medical agents with updated dosage forms that can enhance and optimize local drug delivery and create greater therapeutic effects with fewer side effects. The focus of this review was to provide clear and direct information about the currently available topical therapeutic agents in clinical practice used to cure and/or reduce the incidence of ulcerative symptoms of OM, excluding the associated pain and other coexisting complications such as bacterial and fungal infections. The review also provides recent evidences regarding agents that could be used as promising novel therapies in updated local delivering systems. This will support further encouraging options and approaches for the management of OM and will improve compliance that could be translated in better disease control and survival.
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Affiliation(s)
- Anmar Al-Taie
- Pharmacy Department, Faculty of Pharmacy, Girne American University, North Cyprus, Turkey
| | - Athmar D Al-Shohani
- Department of Pharmaceutics, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
| | - Zahraa Albasry
- Department of Clinical Pharmacy, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
| | - Ataa Altaee
- Department of Clinical Pharmacy, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
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van Sadelhoff JHJ, Hogenkamp A, Wiertsema SP, Harthoorn LF, Loonstra R, Hartog A, Garssen J. A free amino acid-based diet partially prevents symptoms of cow's milk allergy in mice after oral sensitization with whey. Immun Inflamm Dis 2020; 8:93-105. [PMID: 32031763 PMCID: PMC7016843 DOI: 10.1002/iid3.288] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 01/17/2020] [Accepted: 01/19/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Amino acid-based formulas (AAFs) are used for the dietary management of cow's milk allergy (CMA). Whether AAFs have the potential to prevent the development and/or symptoms of CMA is not known. OBJECTIVE The present study evaluated the preventive effects of an amino acid (AA)-based diet on allergic sensitization and symptoms of CMA in mice and aimed to provide insight into the underlying mechanism. METHODS C3H/HeOuJ mice were sensitized with whey protein or with phosphate-buffered saline as sham-sensitized control. Starting 2 weeks before sensitization, mice were fed with either a protein-based diet or an AA-based diet with an AA composition based on that of the AAF Neocate, a commercially available AAF prescribed for the dietary management of CMA. Upon challenge, allergic symptoms, mast cell degranulation, whey-specific immunoglobulin levels, and FoxP3+ cell counts in jejunum sections were assessed. RESULTS Compared to mice fed with the protein-based diet, AA-fed mice had significantly lower acute allergic skin responses. Moreover, the AA-based diet prevented the whey-induced symptoms of anaphylaxis and drop in body temperature. Whereas the AA-based diet had no effect on the levels of serum IgE and mucosal mast cell protease-1 (mMCP-1), AA-fed mice had significantly lower serum IgG2a levels and tended to have lower IgG1 levels (P = .076). In addition, the AA-based diet prevented the whey-induced decrease in FoxP3+ cells. In sham-sensitized mice, no differences between the two diets were observed in any of the tested parameters. CONCLUSION This study demonstrates that an AA-based diet can at least partially prevent allergic symptoms of CMA in mice. Differences in FoxP3+ cell counts and serum levels of IgG2a and IgG1 may suggest enhanced anti-inflammatory and tolerizing capacities in AA-fed mice. This, combined with the absence of effects in sham-sensitized mice indicates that AAFs for the prevention of food allergies may be an interesting concept that warrants further research.
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Affiliation(s)
- Joris H. J. van Sadelhoff
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of ScienceUtrecht UniversityUtrechtThe Netherlands
| | - Astrid Hogenkamp
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of ScienceUtrecht UniversityUtrechtThe Netherlands
| | | | | | | | - Anita Hartog
- CeO ImmunologyDanone Nutricia ResearchUtrechtThe Netherlands
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of ScienceUtrecht UniversityUtrechtThe Netherlands
- CeO ImmunologyDanone Nutricia ResearchUtrechtThe Netherlands
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Anti-Inflammatory Diets and Fatigue. Nutrients 2019; 11:nu11102315. [PMID: 31574939 PMCID: PMC6835556 DOI: 10.3390/nu11102315] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 09/12/2019] [Accepted: 09/25/2019] [Indexed: 12/12/2022] Open
Abstract
Accumulating data indicates a link between a pro-inflammatory status and occurrence of chronic disease-related fatigue. The questions are whether the observed inflammatory profile can be (a) improved by anti-inflammatory diets, and (b) if this improvement can in turn be translated into a significant fatigue reduction. The aim of this narrative review was to investigate the effect of anti-inflammatory nutrients, foods, and diets on inflammatory markers and fatigue in various patient populations. Next to observational and epidemiological studies, a total of 21 human trials have been evaluated in this work. Current available research is indicative, rather than evident, regarding the effectiveness of individuals’ use of single nutrients with anti-inflammatory and fatigue-reducing effects. In contrast, clinical studies demonstrate that a balanced diet with whole grains high in fibers, polyphenol-rich vegetables, and omega-3 fatty acid-rich foods might be able to improve disease-related fatigue symptoms. Nonetheless, further research is needed to clarify conflicting results in the literature and substantiate the promising results from human trials on fatigue.
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Li S, Guo Q, Li S, Zheng H, Chi S, Xu Z, Wang Q. Glutamine protects against LPS-induced inflammation via adjusted NODs signaling and enhanced immunoglobulins secretion in rainbow trout leukocytes. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2019; 98:148-156. [PMID: 31103388 DOI: 10.1016/j.dci.2019.05.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2019] [Revised: 05/13/2019] [Accepted: 05/13/2019] [Indexed: 06/09/2023]
Abstract
To evaluate effects of glutamine (GLN) on fish immune responses, leukocytes were isolated from head kidney of rainbow trout and cultured in GLN-free DMEM media supplemented with different combinations of lipopolysaccharide (LPS) and GLN. LPS significantly increased expression of pro-inflammatory cytokines, while GLN supplementation alleviated LPS-induced inflammation. Leukocytes in +GLN + LPS group showed more active GLN anabolism and catabolism, which signals could be sensed by O-GlcNAcylation, and then affected LPS binding to cell surface (LBP) and adjusted NODs signaling. The mRNA expression of immunoglobulins (Igs) and their receptor (pIgR) was also significantly increased after GLN supplementation. Further analysis showed that GLN increased the percentage of IgM+ B cells and IgT+ B cells, accompanied with the increased IgM and IgT secretion in culture media, which further increased complement C3 expression to perform effector functions. All these results illustrated the regulating mechanism of GLN against LPS-induced inflammation both via adjusted NODs signaling and increased Igs+ B cells to secrete Igs.
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Affiliation(s)
- Shan Li
- Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Haid Central Research Institute, Haid Group, Guangzhou, Guangdong, 511400, China
| | - Qian Guo
- Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
| | - Shuaitong Li
- Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
| | - Haiou Zheng
- Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
| | - Shuyan Chi
- Guangdong South China Sea Key Laboratory of Aquaculture for Aquatic Economic Animals, Guangdong Ocean University, Zhanjiang, Guangdong, 524088, China
| | - Zhen Xu
- Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
| | - Qingchao Wang
- Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
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Lent-Schochet D, McLaughlin M, Ramakrishnan N, Jialal I. Exploratory metabolomics of metabolic syndrome: A status report. World J Diabetes 2019; 10:23-36. [PMID: 30697368 PMCID: PMC6347655 DOI: 10.4239/wjd.v10.i1.23] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 01/04/2019] [Accepted: 01/08/2019] [Indexed: 02/05/2023] Open
Abstract
Metabolic syndrome (MetS) is as a cluster of cardio-metabolic factors that greatly increase the risk of chronic diseases such as type II diabetes mellitus and atherosclerotic cardiovascular disease. In the United States, obesity, physical inactivity, aging, and genetics (to a minor extent) have arisen as risk factors for developing MetS. Although 35% of American adults suffer from MetS, its pathogenesis largely remains unknown. Worse, there is a lack of screening and optimum therapy for this disease. Researchers have consequently turned towards metabolomics to identify biomarkers to better understand MetS. The purpose of this review is to characterize various metabolites and their potential connections to MetS. Numerous studies have also characterized MetS as a disease of increased inflammation, and therefore this review also explores how metabolites play a role in various inflammatory pathways. Our review explores a broad range of metabolites including biogenic amines, branched chain amino acids, aromatic amines, phosphatidylcholines, as well as a variety of other molecules. We will explore their biochemical pathways and their potential role in serving as biomarkers.
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Affiliation(s)
- Daniella Lent-Schochet
- Metabolism and Clinical Pathology, College of Medicine, California Northstate University, Elk Grove, CA 95757, United States
| | - Matthew McLaughlin
- Metabolism and Clinical Pathology, College of Medicine, California Northstate University, Elk Grove, CA 95757, United States
| | - Neeraj Ramakrishnan
- Metabolism and Clinical Pathology, College of Medicine, California Northstate University, Elk Grove, CA 95757, United States
| | - Ishwarlal Jialal
- Metabolism and Clinical Pathology, College of Medicine, California Northstate University, Elk Grove, CA 95757, United States
- VA Medical Center, Mather CA 95655, United States
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Abdel Moneim AE, Guerra-Librero A, Florido J, Shen YQ, Fernández-Gil B, Acuña-Castroviejo D, Escames G. Oral Mucositis: Melatonin Gel an Effective New Treatment. Int J Mol Sci 2017; 18:1003. [PMID: 28481279 PMCID: PMC5454916 DOI: 10.3390/ijms18051003] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Revised: 04/19/2017] [Accepted: 05/03/2017] [Indexed: 12/12/2022] Open
Abstract
The current treatment for cervico-facial cancer involves radio and/or chemotherapy. Unfortunately, cancer therapies can lead to local and systemic complications such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract. Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. However, the role of melatonin in the treatment of mucositis has recently been investigated, and offers an effective alternative therapy in the prevention and/or management of radio and/or chemotherapy-induced mucositis. This review focuses on the pathobiology and management of mucositis in order to improve the quality of cancer patients' lives.
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Affiliation(s)
- Ahmed Esmat Abdel Moneim
- Department of Zoology and Entomology, Faculty of Science, Helwan University, 11795 Cairo, Egypt.
| | - Ana Guerra-Librero
- Centro de Investigación Biomédica, Universidad de Granada, 18016 Granada, Spain.
| | - Javier Florido
- Centro de Investigación Biomédica, Universidad de Granada, 18016 Granada, Spain.
| | - Ying-Qiang Shen
- Centro de Investigación Biomédica, Universidad de Granada, 18016 Granada, Spain.
| | | | - Darío Acuña-Castroviejo
- Centro de Investigación Biomédica, Universidad de Granada, 18016 Granada, Spain.
- CIBERfes, Ibs.Granada, and UGC de Laboratorios Clínicos, Complejo Hospitalario de Granada, 18014 Granada, Spain.
| | - Germaine Escames
- Centro de Investigación Biomédica, Universidad de Granada, 18016 Granada, Spain.
- CIBERfes, Ibs.Granada, and UGC de Laboratorios Clínicos, Complejo Hospitalario de Granada, 18014 Granada, Spain.
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Effects of oral care with glutamine in preventing ventilator-associated pneumonia in neurosurgical intensive care unit patients. Appl Nurs Res 2017; 33:10-14. [DOI: 10.1016/j.apnr.2016.10.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 10/10/2016] [Indexed: 11/21/2022]
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Rittler P, Schiefer B, Demmelmair H, Koletzko B, Roscher AA, Jacobs R, Krick M, Jauch KW, Hartl WH. Effect of Amino Acid Infusion on Human Postoperative Colon Protein Synthesisin Situ. JPEN J Parenter Enteral Nutr 2017; 29:255-61. [PMID: 15961681 DOI: 10.1177/0148607105029004255] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND Amino acids are an integral part of parenteral nutrition because of their anabolic action helping to conserve body protein after surgical stress. At the gastrointestinal tract, an adequate supply of amino acids may be particularly important because of the gut's high rate of protein turnover, cell division, and proliferation. However, no information is available about the effects of amino acids on human intestinal protein metabolism after surgery. METHODS Studies were performed in postabsorptive patients 8-10 days after major abdominal surgery. Mass spectrometry techniques (capillary gas chromatography/combustion isotope ratio mass spectrometry) were used to directly determine the incorporation rate of 1-[13C]-leucine into colon mucosal protein. All subjects had a colostomy, which allowed easy access to the colon mucosa, and consecutive sampling from the same tissue was performed during continuous isotope infusion (0.16 micromol/kg min). Isotopic enrichments were determined at baseline and after a 4-hour infusion of amino acids or after infusion of saline (control group). RESULTS Compared with baseline, infusion of amino acids reduced fractional colon protein synthesis significantly by -29.2 +/- 8.3%. This decrease was also significantly different from the corresponding (insignificant) change during saline infusion (+19.4 +/- 26.9%, p < .05 vs amino acid group). CONCLUSIONS After surgery, an amino acid infusion acutely reduces postoperative colon protein synthesis. This effect possibly may be attributed to interactions of specific amino acids (glutamine) with an altered intestinal immune system and enterocyte activity.
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Affiliation(s)
- Peter Rittler
- Department of Surgery, Klinikum Grosshadern, Munich, Germany
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Marion-Letellier R, Savoye G, Ghosh S. IBD: In Food We Trust. J Crohns Colitis 2016; 10:1351-1361. [PMID: 27194533 DOI: 10.1093/ecco-jcc/jjw106] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 05/10/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Both science and patients associate diet with inflammatory bowel disease [IBD]. There is no doubt that links between IBD and diet are numerous, based on both epidemiological studies and experimental studies. However, scientific evidence to support dietary advice is currently lacking, and dietary counselling for IBD patients is often limited in clinical practice to the improvement of nutrient intake. This review aimed to focus on both patient's beliefs about and molecular mechanisms for crosstalk between nutrients and inflammation. METHODS A literature search using PubMed was performed to identify relevant studies on diet and/or nutrients and their role in IBD. Pubmed [from inception to January 20, 2016] was searched using the terms: 'Crohn', 'colitis',' intestinal epithelial cells', and a list of terms relating to diet or numerous specific nutrients. Terms associated with nutrients were individually tested in the context of IBD. Reference lists from studies selected were manually searched to identify further relevant reports. Manuscripts about diet in the context of IBD from basic science, epidemiological studies, or clinical trials were selected and reviewed. Only articles published in English were included. RESULTS Epidemiological studies highlight the key role of diet in IBD development, and many IBD patients report diet as a triggering factor in relapse of disease. In addition, we present research on the impact of nutrients on innate immunity. CONCLUSION Diet may offer an alternative approach to restoring deficient innate immunity in IBD, and this may be the scientific rationale for providing dietary counselling for IBD patients.
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Affiliation(s)
| | - Guillaume Savoye
- INSERM Unit UMR1073, Rouen University and Rouen University Hospital, Rouen cedex, France.,Department of Gastroenterology, Rouen University Hospital, Rouen cedex, France
| | - Subrata Ghosh
- Division of Gastroenterology, University of Calgary, Alberta, Canada
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Lee YM, Kim MJ, Kim Y, Kim H. Glutamine Deprivation Causes Hydrogen Peroxide-induced Interleukin-8 Expression via Jak1/Stat3 Activation in Gastric Epithelial AGS Cells. J Cancer Prev 2015; 20:179-84. [PMID: 26473156 PMCID: PMC4597806 DOI: 10.15430/jcp.2015.20.3.179] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
BACKGROUND The Janus kinase (Jak)/Signal transducers of activated transcription (Stat) pathway is an upstream signaling pathway for NF-κB activation in Helicobacter pylori-induced interleukin (IL)-8 production in gastric epithelial AGS cells. H. pylori activates NADPH oxidase and produces hydrogen peroxide, which activates Jak1/Stat3 in AGS cells. Therefore, hydrogen peroxide may be critical for IL-8 production via Jak/Stat activation in gastric epithelial cells. Glutamine is depleted during severe injury and stress and contributes to the formation of glutathione (GSH), which is involved in conversion of hydrogen peroxide into water as a cofactor for GSH peroxidase. METHODS We investigated whether glutamine deprivation induces hydrogen peroxide-mediated IL-8 production and whether hydrogen peroxide activates Jak1/Stat3 to induce IL-8 in AGS cells. Cells were cultured in the presence or absence of glutamine or hydrogen peroxide, with or without GSH or a the Jak/Stat specific inhibitor AG490. RESULTS Glutamine deprivation decreased GSH levels, but increased levels of hydrogen peroxide and IL-8, an effect that was inhibited by treatment with GSH. Hydrogen peroxide induced the activation of Jak1/Stat3 time-dependently. AG490 suppressed hydrogen peroxide- induced activation of Jak1/Stat3 and IL-8 expression in AGS cells, but did not affect levels of reactive oxygen species in AGS cells. CONCLUSIONS In gastric epithelial AGS cells, glutamine deprivation increases hydrogen peroxide levels and IL-8 expression, which may be mediated by Jak1/Stat3 activation. Glutamine supplementation may be beneficial for preventing gastric inflammation by suppressing hydrogen peroxide-mediated Jak1/Stat3 activation and therefore, reducing IL-8 production. Scavenging hydrogen peroxide or targeting Jak1/Stat3 may also prevent oxidant-mediated gastric inflammation.
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Affiliation(s)
- Yun Mi Lee
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea
| | - Mi Jung Kim
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea
| | - Youngha Kim
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea
| | - Hyeyoung Kim
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea
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Impact of nutrition on brain development and its neuroprotective implications following preterm birth. Pediatr Res 2015; 77:148-55. [PMID: 25314585 PMCID: PMC4291511 DOI: 10.1038/pr.2014.171] [Citation(s) in RCA: 144] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 09/30/2014] [Indexed: 01/08/2023]
Abstract
The impact of nutrition on brain development in preterm infants has been increasingly appreciated. Early postnatal growth and nutrient intake have been demonstrated to influence brain growth and maturation with subsequent effects on neurodevelopment that persist into childhood and adolescence. Nutrition could also potentially protect against injury. Inflammation and perinatal infection play a crucial role in the pathogenesis of white matter injury, the most common pattern of brain injury in preterm infants. Therefore, nutritional components with immunomodulatory and/or anti-inflammatory effects may serve as neuroprotective agents. Moreover, growing evidence supports the existence of a microbiome-gut-brain axis. The microbiome is thought to interact with the brain through immunological, endocrine, and neural pathways. Consequently, nutritional components that may influence gut microbiota may also exert beneficial effects on the developing brain. Based on these properties, probiotics, prebiotic oligosaccharides, and certain amino acids are potential candidates for neuroprotection. In addition, the amino acid glutamine has been associated with a decrease in infectious morbidity in preterm infants. In conclusion, early postnatal nutrition is of major importance for brain growth and maturation. Additionally, certain nutritional components might play a neuroprotective role against white matter injury, through modulation of inflammation and infection, and may influence the microbiome-gut-brain axis.
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Palmieri EM, Spera I, Menga A, Infantino V, Iacobazzi V, Castegna A. Glutamine synthetase desensitizes differentiated adipocytes to proinflammatory stimuli by raising intracellular glutamine levels. FEBS Lett 2014; 588:4807-14. [PMID: 25451225 DOI: 10.1016/j.febslet.2014.11.015] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Revised: 10/09/2014] [Accepted: 11/11/2014] [Indexed: 01/16/2023]
Abstract
The role of glutamine synthetase (GS) during adipocyte differentiation is unclear. Here, we assess the impact of GS on the adipocytic response to a proinflammatory challenge at different differentiation stages. GS expression at the late stages of differentiation desensitized mature adipocytes to bacterial lipopolysaccharide (LPS) by increasing intracellular glutamine levels. Furthermore, LPS-activated mature adipocytes were unable to produce inflammatory mediators; LPS sensitivity was rescued following GS inhibition and the associated drop in intracellular glutamine levels. The ability of adipocytes to differentially respond to LPS during differentiation negatively correlates to GS expression and intracellular glutamine levels. Hence, modulation of intracellular glutamine levels by GS expression represents an endogenous mechanism through which mature adipocytes control the inflammatory response.
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Affiliation(s)
- Erika Mariana Palmieri
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy
| | - Iolanda Spera
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy
| | - Alessio Menga
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy
| | | | - Vito Iacobazzi
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy; CNR Institute of Biomembranes and Bioenergetics, Bari, Italy
| | - Alessandra Castegna
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
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Scrimgeour AG, Condlin ML. Nutritional Treatment for Traumatic Brain Injury. J Neurotrauma 2014; 31:989-99. [DOI: 10.1089/neu.2013.3234] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Affiliation(s)
- Angus G. Scrimgeour
- Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts
| | - Michelle L. Condlin
- Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts
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Glutamine deprivation induces interleukin-8 expression in ataxia telangiectasia fibroblasts. Inflamm Res 2014; 63:347-56. [PMID: 24413629 DOI: 10.1007/s00011-013-0706-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2013] [Revised: 12/23/2013] [Accepted: 12/30/2013] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVE To investigate whether glutamine deprivation induces expression of inflammatory cytokine interleukin-8 (IL-8) by determining NF-κB activity and levels of oxidative indices (ROS, reactive oxygen species; hydrogen peroxide; GSH, glutathione) in fibroblasts isolated from patients with ataxia telangiectasia (A-T). MATERIALS We used A-T fibroblasts stably transfected with empty vector (Mock) or with human full-length ataxia telangiectasia mutated (ATM) cDNA (YZ5) and mouse embryonic fibroblasts (MEFs) transiently transfected with ATM small interfering RNA (siRNA) or with non-specific control siRNA. TREATMENT The cells were cultured with or without glutamine or GSH. METHODS ROS levels were determined using a fluorescence reader and confocal microscopy. IL-8 or murine IL-8 homolog, keratinocyte chemoattractant (KC), and hydrogen peroxide levels in the medium were determined by enzyme-linked immunosorbent assay and colorimetric assay. GSH level was assessed by enzymatic assay, while IL-8 (KC) mRNA level was measured by reverse transcription-polymerase chain reaction (RT-PCR) and/or quantitative real-time PCR. NF-κB DNA-binding activity was determined by electrophoretic mobility shift assay. Catalase activity and ATM protein levels were determined by O2 generation and Western blotting. RESULTS While glutamine deprivation induced IL-8 expression and increased NF-κB DNA-binding activity in Mock cells, both processes were decreased by treatment of cells with glutamine or GSH or both glutamine and GSH. Glutamine deprivation had no effect on IL-8 expression or NF-κB DNA-binding activity in YZ5 cells. Glutamine-deprived Mock cells had higher oxidative stress indices (increases in ROS and hydrogen peroxide, reduction in GSH) than glutamine-deprived YZ5 cells. In Mock cells, glutamine deprivation-induced oxidative stress indices were suppressed by treatment with glutamine or GSH or both glutamine and GSH. GSH levels and catalase activity were lower in Mock cells than YZ5 cells. MEFs transfected with ATM siRNA and cultured without glutamine showed higher levels of ROS and IL-8 than those transfected with negative control siRNA; increased levels of ROS and IL-8 were suppressed by the treatment of glutamine. CONCLUSION Glutamine deprivation induces ROS production, NF-κB activation, and IL-8 expression as well as a reduction in GSH in A-T fibroblasts, all of which are attenuated by glutamine supplementation.
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Javed S, Mejías-Luque R, Kalali B, Bolz C, Gerhard M. Helicobacter bilis gamma-glutamyltranspeptidase enhances inflammatory stress response via oxidative stress in colon epithelial cells. PLoS One 2013; 8:e73160. [PMID: 24009737 PMCID: PMC3751837 DOI: 10.1371/journal.pone.0073160] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2013] [Accepted: 07/17/2013] [Indexed: 12/20/2022] Open
Abstract
Helicobacter bilis (H. bilis) infection is associated with cases of inflammatory bowel Disease, thyphlocolitis, hepatitis and cholecystitis. However, little is known about the bacterial virulence determinants or the molecular mechanisms involved. Recently, H. bilis γ-glutamyltranspeptidase (HBgGT) was shown to be a virulence factor decreasing host cell viability. Bacterial gGTs play a key role in synthesis and degradation of glutathione and enables the bacteria to utilize extracellular glutamine and glutathione as sources of glutamate. gGT-mediated loss of cell viability has so far been linked to DNA damage via oxidative stress, but the signaling cascades involved herein have not been described. In this study, we identified enhanced ROS production induced by HBgGT as a central factor involved in the activation of the oxidative stress response cascades, which finally activate CREB, AP-1 and NF-κB in H. bilis infected colon cancer cells. IL-8, an important pro-inflammatory chemokine that is a common downstream target of these transcription factors, was up-regulated upon H. bilis infection in an HBgGT dependent manner. Moreover, the induction of these signaling responses and inflammatory cytokine production in host cells could be linked to HBgGT-mediated glutamine deprivation. This study implicates for the first time HBgGT as an important regulator of signaling cascades regulating inflammation in H. bilis infected host epithelial cells that could be responsible for induction of inflammatory disorders by the bacterium.
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Affiliation(s)
- Sundus Javed
- Department of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany
| | - Raquel Mejías-Luque
- Department of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany
| | - Behnam Kalali
- Department of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany
| | - Christian Bolz
- Department of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany
| | - Markus Gerhard
- Department of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany
- * E-mail:
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Regulation of intestinal protein metabolism by amino acids. Amino Acids 2012; 45:443-50. [DOI: 10.1007/s00726-012-1325-8] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2012] [Accepted: 05/15/2012] [Indexed: 12/24/2022]
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Zhong X, Li W, Huang X, Wang Y, Zhang L, Zhou Y, Hussain A, Wang T. Effects of glutamine supplementation on the immune status in weaning piglets with intrauterine growth retardation. Arch Anim Nutr 2012; 66:347-56. [PMID: 22962945 DOI: 10.1080/1745039x.2012.683325] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Neonates with intrauterine growth retardation (IUGR) often suffer from impaired cellular immunity, and weaning may further aggravate adverse effects of IUGR on development and function of the immune system. In this study, we investigated effects of glutamine supplementation on immune status in the intestines of weaning pigs with IUGR, focusing on molecular mechanisms underlying altered immune response. Piglets with IUGR were weaned at 21 days of age and received orally 1.22 g alanine or 1 g glutamine per kg body weight every 12 h. Weight gain and intestinal weight of weaning piglets were increased by glutamine supplementation. Levels of serum IgG in piglets supplemented with glutamine were increased compared with Control piglets. The production of IL-1 and IL-8 in the serum and jejunum was decreased by glutamine supplementation, whereas the levels of IL-4 in the serum and the concentrations of IL-4 and IL-10 in the jejunum were increased. The expression of heat shock protein 70 (Hsp70) in the jejunum was increased by glutamine supplementation, but the degradation of inhibitor κB and the activity of nuclear factor-κB (NF-κB) were decreased. In conclusion, glutamine supplementation enhanced immune response in weaning piglets with IUGR. The effects of glutamine in IUGR are associated with increased Hsp70 expression and suppression of NF-κB activation.
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Affiliation(s)
- Xiang Zhong
- College of Animal Science and Technology , Nanjing Agricultural University, Nanjing, Jiangsu, China
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Lechowski S, Feilhauer K, Staib L, Coëffier M, Bischoff SC, Lorentz A. Combined arginine and glutamine decrease release of de novo synthesized leukotrienes and expression of proinflammatory cytokines in activated human intestinal mast cells. Eur J Nutr 2012; 52:505-12. [DOI: 10.1007/s00394-012-0353-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2011] [Accepted: 03/28/2012] [Indexed: 01/08/2023]
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Rodríguez-Caballero A, Torres-Lagares D, Robles-García M, Pachón-Ibáñez J, González-Padilla D, Gutiérrez-Pérez JL. Cancer treatment-induced oral mucositis: a critical review. Int J Oral Maxillofac Surg 2011; 41:225-38. [PMID: 22071451 DOI: 10.1016/j.ijom.2011.10.011] [Citation(s) in RCA: 113] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2010] [Revised: 10/01/2011] [Accepted: 10/10/2011] [Indexed: 01/09/2023]
Abstract
Head and neck cancer represents one of the main oncological problems. Its treatment, radiotherapy and chemotherapy leads to mucositis, and other side effects. The authors reviewed high-quality evidence published over the last 25 years on the treatment of cancer treatment-induced oral mucositis. A Medline search for double blind randomized controlled clinical trials between 1985 and 2010 was carried out. The keywords were oral mucositis, radiotherapy, chemotherapy, and head and neck. The different therapeutic approaches found for cancer treatment-induced oral mucositis included: intensive oral hygiene care; use of topical antiseptics and antimicrobial agents; use of anti-inflammatory agents; cytokines and growth factors; locally applied non-pharmacological methods; antioxidants; immune modulators; and homoeopathic agents. To date, no intervention has been able to prevent and treat oral mucositis on its own. It is necessary to combine interventions that act on the different phases of mucositis. It is still unclear which strategies reduce oral mucositis, as there is not enough evidence that describes a treatment with a proven efficiency and is superior to the other treatments for this condition.
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Alanyl-glutamine restores maternal deprivation-induced TLR4 levels in a rat neonatal model. Clin Nutr 2011; 30:672-7. [DOI: 10.1016/j.clnu.2011.04.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2010] [Revised: 03/29/2011] [Accepted: 04/14/2011] [Indexed: 12/27/2022]
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Coëffier M, Marion-Letellier R, Déchelotte P. Potential for amino acids supplementation during inflammatory bowel diseases. Inflamm Bowel Dis 2010; 16:518-24. [PMID: 19572337 DOI: 10.1002/ibd.21017] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The pathophysiology of inflammatory bowel diseases (IBDs) is multifactorial and involves interactions of gut luminal content with mucosal barrier and especially immune cells. Malnutrition is a frequent issue during IBD flares, especially in Crohn's disease (CD) patients, and nutritional support is frequently used to treat malnutrition but also in an attempt to modulate intestinal inflammation. The use of oral or enteral nutrition intervention in IBDs may be effective, alone or in combination with drugs, to achieve and maintain remission. However, standard diets are less effective than new-generation biotherapies and could be improved by supplementation with specific immunomodulatory amino acids. Experimental studies evaluating glutamine, the preferential substrate for enterocytes, are promising. Some clinical studies with oral glutamine in CD are until now disappointing, but new formulations and targeting could enhance glutamine efficacy at the site of mucosal lesions. The role of arginine, involved in nitric oxide and polyamines synthesis, still remains debated. However, the effects of these amino acids in IBD have been poorly documented in humans. Other candidates like glycine, cysteine, histidine, or taurine should also be evaluated in the future.
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Affiliation(s)
- Moïse Coëffier
- Appareil Digestif Environnement Nutrition (ADEN EA4311), Institute for Biomedical Research, European Institute for Peptide Research (IFRMP 23), Rouen University and Rouen University Hospital, Rouen, France.
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You WC, Lin WC, Huang JT, Hsieh CC. Indigowood root extract protects hematopoietic cells, reduces tissue damage and modulates inflammatory cytokines after total-body irradiation: does Indirubin play a role in radioprotection? PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2009; 16:1105-1111. [PMID: 19589667 PMCID: PMC7126534 DOI: 10.1016/j.phymed.2009.05.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/03/2009] [Revised: 04/20/2009] [Accepted: 05/14/2009] [Indexed: 05/28/2023]
Abstract
Radix of Isatis indigotica (indigowood root, IR) has been used in traditional medicine for its potential anti-inflammatory effect. The purpose of this study is to investigate the radioprotective effects of radiation caused damages in hematopoietic system and normal tissues in mice. A total of 57 BALB/c mice were randomized into six treatment groups: control, IR treatment (0.195, 0.585 and 1.170 g/kg, p.o. daily), L-glutamine (0.520 g/kg) and sham group. All mice except the sham group were irradiated and then administered for one week. The radioprotective effect on hematopoietic system, serum cytokines, and intestinal toxicity was studied. Protective effects on spleen and thymus are found in IR-treated groups. IR assisted in restoration of leukocytopenia after whole mice irradiation with significant reduction of serum TNF-alpha, IL-1beta, and IL-6. These enhancements of hematopoietic effects are due to an increase in the serum G-CSF concentration in IR treated groups. In histopathological assessment, significant improvement of intestine toxicity is observed in high-dose IR and L-glutamine group. Evidences show that IR has potentials to be a radioprotector, especially in recovery of hematopoietic system, reduction of inflammatory cytokines and intestinal toxicity. Indirubin may play a crucial role, but the underlying mechanism is not very clear and warrants further studies.
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Affiliation(s)
- Weir Chiang You
- Department of Radiation Oncology, Lin Shin Hospital, Taichung, Taiwan
- Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan
| | - Wen Chuan Lin
- Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
| | - Jia Tsz Huang
- Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan
| | - Chang Chi Hsieh
- Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
- Department of Animal Science and Biotechnology, Tunghai University, No. 181, Section 3, Taichung Harbor Road, Taichung 40704, Taiwan
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Cytokine responses in very low birth weight infants receiving glutamine-enriched enteral nutrition. J Pediatr Gastroenterol Nutr 2009; 48:94-101. [PMID: 19172131 DOI: 10.1097/mpg.0b013e3181805116] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE Very low birth weight (VLBW) infants receiving glutamine-enriched enteral nutrition may present with a lower infection rate, which may result from enhanced antimicrobial innate or Th1 cytokine responses. We investigated whether glutamine-enriched enteral nutrition in VLBW infants increased these cytokine responses following in vitro stimulation of whole blood cells. METHODS In a double-blind, placebo-controlled, randomized controlled trial, VLBW infants (gestational age <32 weeks and/or birth weight <1500 g) received enteral glutamine supplementation (0.3 g x kg(-1) x day(-1)) or isonitrogenous placebo supplementation (alanine) between days 3 and 30 of life. Cytokine responses following in vitro whole blood cell stimulation with anti-(alpha)CD3/alphaCD28 or lipopolysaccharide were analyzed by cytometric bead array at 3 time points: before the start of the study, at day 7 of life, and at day 14 of life. RESULTS Baseline patient and nutritional characteristics were not different between groups. At least 2 blood samples were analyzed in 25 of 52 (48%) and 38 of 50 (76%) infants in the glutamine-supplemented and control groups, respectively. Glutamine-enriched enteral nutrition was not associated with significant alterations in cytokine responses (interferon-gamma, tumor necrosis factor-alpha, interleukin [IL]-2, IL-4, IL-5, and IL-10) of peripheral blood cells upon stimulation with either anti-alphaCD3/alphaCD28 or lipopolysaccharide. CONCLUSIONS We hypothesize that glutamine-enriched enteral nutrition decreases the infection rate in VLBW infants by influencing the mucosal and not the systemic immune system.
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Lecleire S, Hassan A, Marion-Letellier R, Antonietti M, Savoye G, Bôle-Feysot C, Lerebours E, Ducrotté P, Déchelotte P, Coëffier M. Combined glutamine and arginine decrease proinflammatory cytokine production by biopsies from Crohn's patients in association with changes in nuclear factor-kappaB and p38 mitogen-activated protein kinase pathways. J Nutr 2008; 138:2481-6. [PMID: 19022976 DOI: 10.3945/jn.108.099127] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Glutamine (Gln) and arginine (Arg) are conditionally essential amino acids with immunomodulatory properties. The aim of the study was to assess the effects of Gln and Arg alone or in combination on cytokine release by cultured colonic biopsies from patients with active Crohn's disease (CD). Ten consecutive patients [mean (range) age 26 (18-39) y] with active colonic CD (mean CD activity index: 383.7 +/- 129.8) were prospectively included in the study. Eight colonic biopsies were obtained via a colonoscopy and incubated during 18 h with low (physiological) or high (pharmacological) doses of Arg (0.1 or 2 mmol/L designated as Arg(low) or Arg(high), respectively) and Gln (0.6 or 10 mmol/L designated as Gln(low) or Gln(high), respectively). The concentrations of cytokines [interleukin (IL)-4, IL-10, IL-8, IL-6, tumor necrosis factor-alpha (TNFalpha), IL-1beta, interferon-gamma) were assessed by ELISA, and nitric oxide (NO) production was evaluated by Griess assay. Nuclear factor (NF)-kappaB p65 subunit, inhibitor of NFkappaB-alpha, and p38 mitogen-activated protein kinase (MAPK) were assessed by immunoblotting. Arg(high)/Gln(high) decreased the production of TNFalpha, IL-1beta, IL-8, and IL-6 (each P < 0.01). Arg(low)/Gln(high) decreased IL-6 and IL-8 production (both P < 0.01), whereas Arg(high)/Gln(low) did not affect cytokine and NO production. Arg(low)/Gln(high) and Arg(high)/Gln(high) decreased NF-kappaB p65 subunit expression, whereas p38 MAPK was decreased only by Arg(high)/Gln(high). Combined pharmacological doses of Arg and Gln decreased TNFalpha and the main proinflammatory cytokines release in active colonic CD biopsies via NF-kappaB and p38 MAPK pathways. These results could be the basis of prospective studies evaluating the effects of enteral supply of combined Arg and Gln during active CD.
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Affiliation(s)
- Stéphane Lecleire
- Appareil Digestif Environnement Nutrition EA4311, Institute for Biomedical Research, IFRMP23, Rouen University and Rouen University Hospital, Rouen, France
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Roggenbuck C, Lammert F, Berthold HK, Giese T, Stallmach A, Stehle P, Ellinger S. High-dose oral supplementation of antioxidants and glutamine improves the antioxidant status in patients with Crohn's disease: A pilot study. ACTA ACUST UNITED AC 2008. [DOI: 10.1016/j.eclnm.2008.06.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Abstract
Oral mucositis is a clinically important and sometimes dose-limiting complication of cancer therapy. Mucositis lesions can be painful, affect nutrition and quality of life, and have a significant economic impact. The pathogenesis of oral mucositis is multifactorial and complex. This review discusses the morbidity, economic impact, pathogenesis and clinical course of mucositis. Current clinical management of oral mucositis is largely focused on palliative measures such as pain management, nutritional support and maintenance of good oral hygiene. However, several promising therapeutic agents are in various stages of clinical development for the management of oral mucositis. These agents are discussed in the context of recently updated evidence-based clinical management guidelines.
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Affiliation(s)
- Rajesh V Lalla
- Division of Oral Medicine, Department of Oral Health and Diagnostic Sciences, University of Connecticut Health Center MC 1605, 263 Farmington Avenue, Farmington, CT 06030, USA.
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Luo M, Bazargan N, Griffith DP, Estívariz CF, Leader LM, Easley KA, Daignault NM, Hao L, Meddings JB, Galloway JR, Blumberg JB, Jones DP, Ziegler TR. Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: a pilot study. Clin Nutr 2008; 27:297-306. [PMID: 18258342 DOI: 10.1016/j.clnu.2007.12.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2007] [Revised: 11/01/2007] [Accepted: 12/05/2007] [Indexed: 10/22/2022]
Abstract
BACKGROUND Glutamine (Gln) may become conditionally indispensable during critical illness. The short-term metabolic effects of enteral versus parenteral Gln supplementation are unknown in this clinical setting. OBJECTIVES We studied metabolic effects of intravenous (i.v.) alanyl-Gln dipeptide (AG) supplementation and enteral (e.n.) AG supplementation on plasma Gln concentration, antioxidant status, plasma lymphocyte subset number, gut permeability and nitrogen balance in adult critically ill patients requiring tube feeding compared to a control group not receiving Gln supplementation. METHODS In a double-blind, pilot clinical trial, 44 medical and surgical ICU patients received identical Gln-free tube feedings 24 h/day and were randomized to either isonitrogenous control (n=15), e.n. AG (n=15) or i.v. AG (n=14) groups (AG). Twelve patients were discontinued from the study. The goal AG dose was 0.5 g/kg/day. Biochemical and metabolic endpoints were measured at baseline and on day 9 (plasma Gln, antioxidant indices, lymphocyte subsets; serum IGF-1 and IGF-binding protein-3; intestinal permeability). Nitrogen balance was determined between study days 6 and 8. RESULTS Illness severity indices, clinical demographics, enteral energy and nitrogen intake and major biochemical indices were similar between groups during study. Plasma Gln was higher in the i.v. AG (565+/-119 microM, mean+/-SEM) vs the e.n. AG (411+/-27 microM) group by day 9 (p=0.039); however, subjects in the i.v. AG group received a higher dose of AG (i.v. AG 0.50 versus e.n. AG 0.32+/-0.02 g/kg/day; p<0.001). E.n. AG subjects showed a significant increase in plasma alpha-tocopherol levels over time and maintained plasma gamma-tocopherol concentrations. There were no differences between groups for plasma concentrations of vitamin C, glutathione, malondialdehyde (MDA), T-lymphocyte subsets, intestinal permeability or nitrogen balance. CONCLUSIONS This study showed that alanyl-Gln administration by enteral or parenteral routes did not appear to affect antioxidant capacity or oxidative stress markers, T-lymphocyte subset (CD-3, CD-4, CD-8) number, gut barrier function or whole-body protein metabolism compared to unsupplemented ICU patients requiring enteral tube feeding. Enteral Gln appeared to maintain plasma tocopherol levels in this pilot metabolic study.
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Affiliation(s)
- Menghua Luo
- Department of Medicine, Emory University, 1364 Clifton Road, Atlanta, GA 30322, United States
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Feng D, Xu W, Chen G, Hang C, Gao H, Yin H. Influence of glutamine on intestinal inflammatory response, mucosa structure alterations and apoptosis following traumatic brain injury in rats. J Int Med Res 2007; 35:644-56. [PMID: 17900404 DOI: 10.1177/147323000703500509] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Traumatic brain injury (TBI) can induce a persistent inflammatory response, histopathological changes and apoptosis in the intestine. Glutamine has been shown to reduce bacterial translocation and maintain intestine mucosal integrity, but its effects on the inflammatory response, structural alterations and apoptosis in intestinal mucosa following TBI have not been previously investigated. Using the weight-drop method, a right parietal cortical contusion was induced in rats and, for the next 5 days, they were fed either chow alone or chow mixed with glutamine. Intestinal tissue samples were then removed for analysis. Following TBI, glutamine supplementation was found to: decrease intestinal concentrations of interleukin (IL) -1beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6; downregulate intercellular adhesion molecule-1 (ICAM-1) expression; attenuate TBI-induced damage to the intestine structure; and reduce apoptosis. These results suggest that post-TBI glutamine administration could suppress intestinal inflammation, protect intestinal mucosal structure and reduce mucosal apoptosis.
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Affiliation(s)
- D Feng
- Department of Neurosurgery, Jiangyin Hospital, School of Medicine, Southeast University, Jiangyin, Jiangsu Province, China.
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Brasse-Lagnel C, Lavoinne A, Loeber D, Fairand A, Bôle-Feysot C, Deniel N, Husson A. Glutamine and interleukin-1β interact at the level of Sp1 and nuclear factor-κB to regulate argininosuccinate synthetase gene expression. FEBS J 2007; 274:5250-62. [PMID: 17892496 DOI: 10.1111/j.1742-4658.2007.06047.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
We previously demonstrated that the expression of the argininosuccinate synthetase (ASS) gene, a key step in nitric oxide production, is stimulated either by interleukin-1beta[Brasse-Lagnel et al. (2005) Biochimie 87, 403-9] or by glutamine in Caco-2 cells [Brasse-Lagnel et al. (2003) J. Biol. Chem. 278, 52504-10], through the activation of transcription factors nuclear factor-kappaB and Sp1, respectively. In these cells, the fact that glutamine stimulated the expression of a gene induced by pro-inflammatory factors appeared paradoxical as the amino acid is known to exert anti-inflammatory properties in intestinal cells. We therefore investigated the effect of simultaneous addition of both glutamine and interleukin-1beta on ASS gene expression in Caco-2 cells. In the presence of both compounds for 4 h, the increases in ASS activity, protein amount and mRNA level were almost totally inhibited, implying a reciprocal inhibition between the amino acid and the cytokine. The inhibition was exerted at the level of the transcription factors Sp1 and nuclear-kappaB: (a) interleukin-1beta inhibited the glutamine-stimulated DNA-binding of Sp1, which might be related to a decrease of its glutamine-induced O-glycosylation, and (b) glutamine induced per se a decrease in the amount of nuclear p65 protein without affecting the stimulating effect of interleukin-1beta on nuclear factor-kappaB, which might be related to the metabolism of glutamine into glutamate. The present results constitute the first demonstration of a reciprocal inhibition between the effects of an amino acid and a cytokine on gene expression, and provide a molecular basis for the protective role of glutamine against inflammation in the intestine.
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Affiliation(s)
- Carole Brasse-Lagnel
- Groupe Appareil Digestif, Environnement et Nutrition, Institut Fédératif de Recherches Multidisciplinaires sur Peptides, Université de Rouen, France
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Abstract
Despite the great advances in our understanding of the pathophysiology of acute pancreatitis, no specific therapy has emerged, and treatment remains supportive. In patients with the severe form of the disease, in which mortality remains high at 20% to 30%, the function of the upper gastrointestinal tract is disturbed due to extrinsic compression by the inflamed and swollen pancreas, and normal eating is impossible. Such patients often develop multiple organ failure, necessitating intensive-care management and artificial ventilation for weeks on end. In this setting, protein catabolism will rapidly result in protein deficiency and further complications unless nutritional support is commenced. Recent studies have shown that, despite the risk of disease exacerbation through pancreatic stimulation, enteral feeding is more effective than parenteral feeding in improving outcome. Experimental studies suggest that this can be attributed to its content of specific immunomodulating nutrients, such as glutamine, arginine, and n-3 fatty acids, and by its stabilizing effect on the gut flora through the provision of prebiotics. Further studies are indicated to examine whether dietary enrichment with these substrates, along with regulation of the gut bacteria with probiotics, can improve outcome further.
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Affiliation(s)
- Refaat A F Hegazi
- Division of Gastroenterology, University of Pittsburgh Medical School, Pittsburgh, PA 15213, USA
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Belmonte L, Coëffier M, Le Pessot F, Miralles-Barrachina O, Hiron M, Leplingard A, Lemeland JF, Hecketsweiler B, Daveau M, Ducrotté P, Déchelotte P. Effects of glutamine supplementation on gut barrier, glutathione content and acute phase response in malnourished rats during inflammatory shock. World J Gastroenterol 2007; 13:2833-40. [PMID: 17569119 PMCID: PMC4395635 DOI: 10.3748/wjg.v13.i20.2833] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the effect of glutamine on intestinal mucosa integrity, glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock.
METHODS: Plasma acute phase proteins (APP), jejunal APP mRNA levels, liver and jejunal glutathione concentrations were measured before and one, three and seven days after turpentine injection in 4 groups of control, protein-restricted, protein-restricted rats supplemented with glutamine or protein powder. Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed.
RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height, and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil, glutamine supplementation restored villus heights and glutathione concentration (3.24 ± 1.05 vs 1.72 ± 0.46 μmol/g tissue, P < 0.05) in the jejunum, whereas in the liver glutathione remained low. Glutamine markedly increased jejunal α1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation.
CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model.
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Affiliation(s)
- Liliana Belmonte
- ADEN EA3234, Institut Hospitalo-Universitaire de Recherche Biomédicale and Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, Rouen, France
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Peterson DE, Jones JB, Petit RG. Randomized, placebo-controlled trial of Saforis for prevention and treatment of oral mucositis in breast cancer patients receiving anthracycline-based chemotherapy. Cancer 2007; 109:322-31. [PMID: 17154160 DOI: 10.1002/cncr.22384] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Oral mucositis (OM) is a frequent complication of mucotoxic cancer therapy, causing significant oral pain, increased infection risk, and impaired functioning. The efficacy and safety of Saforis (glutamine) powder in UpTec for oral suspension was evaluated for the prevention and treatment of OM. METHODS Three hundred twenty-six patients developing World Health Organization (WHO) grade >or=2 OM during a chemotherapy screening cycle were randomized to Saforis (n = 163) or placebo (n = 163) 3 times/day during their next chemotherapy cycle (Treatment Cycle 1). Patients were crossed over to the alternate treatment during Treatment Cycle 2. As prespecified in the statistical plan, because of a carryover effect in Treatment Cycle 2 the primary efficacy analysis was based on Treatment Cycle 1 only. RESULTS Compared with placebo, Saforis significantly reduced the incidence of clinically significant WHO grade >or=2 OM (38.7% vs. 49.7%; P = .026) and severe WHO grade >or=3 OM (1.2% vs. 6.7%; P = .005) in Treatment Cycle 1. Saforis also significantly reduced the worst Oral Mucositis Assessment Scale ulceration score in Treatment Cycle 1 compared with placebo (mean, 0.23 +/- 0.39 vs. 0.32 +/- 0.45; P = .013). Patients receiving Saforis in Treatment Cycle 1 had a lower-than-expected OM incidence when crossed over to placebo in Treatment Cycle 2, indicating a significant carryover effect (P = .027). The incidence of treatment-emergent adverse events was similar between groups. CONCLUSIONS Saforis is safe and effective for preventing and treating OM in patients receiving mucotoxic cancer chemotherapy.
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Affiliation(s)
- Douglas E Peterson
- Department of Oral Health and Diagnostic Sciences, School of Dental Medicine, and Head & Neck/Oral Oncology Program, Neag Comprehensive Cancer Center, University of Connecticut Health Center, Farmington, Connecticut 06030-1605, USA.
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Abstract
PURPOSE OF REVIEW The potential efficacy of glutamine and glutamate as nutritional supplements for premature infants was originally met with enthusiasm. Despite no evidence of toxicity in the clinical trials, the use of glutamine has not become routine. In certain studies, the benefits seem clear, whereas in others, benefits have not been demonstrated. Specific designs for studies have been difficult, targets based on mechanistic frameworks have been poorly defined, study populations are heterogeneous and putative mechanisms of glutamine action are multifold. Our purpose is to review recent findings pertaining to (1) the action and mechanisms of glutamine and glutamate in the gastrointestinal tract, and (2) the future directions for glutamine and glutamate research with a focus on the premature neonate. RECENT FINDINGS Studies elucidating mechanisms of glutamine action include tissue protection, immune modulation, preservation of glutathione and antioxidant capacity, preservation of metabolism, decreased intestinal apoptosis, and enhancement of heat shock proteins. The ability to decrease gastrointestinal-derived systemic inflammation appears to have especially significant implications for premature infants. SUMMARY We review recent studies of mechanisms of glutamine and glutamate action, pertinent clinical trials, and suggest areas for future research based on these mechanisms.
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Affiliation(s)
- Josef Neu
- Department of Pediatrics, Neonatal Gastroenterology and Biochemical Nutrition Laboratory, University of Florida, Gainesville, Florida, USA.
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Lobo DN, Williams RN, Welch NT, Aloysius MM, Nunes QM, Padmanabhan J, Crowe JR, Iftikhar SY, Parsons SL, Neal KR, Allison SP, Rowlands BJ. Early postoperative jejunostomy feeding with an immune modulating diet in patients undergoing resectional surgery for upper gastrointestinal cancer: A prospective, randomized, controlled, double-blind study. Clin Nutr 2006; 25:716-26. [PMID: 16777271 DOI: 10.1016/j.clnu.2006.04.007] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2005] [Revised: 04/14/2006] [Accepted: 04/21/2006] [Indexed: 01/18/2023]
Abstract
BACKGROUND The provision of perioperative immune modulating enteral feeds after major surgery may result in reduced infective complications, but meta-analyses have not demonstrated a survival advantage. The aim of this study was to determine whether early postoperative immune modulating jejunostomy feeding results in reduced infective complications in patients undergoing resectional surgery for upper gastrointestinal cancer. METHODS A total of 120 patients undergoing resection for cancers of the pancreas, oesophagus and stomach were randomized in a double-blind manner to receive jejunostomy feeding with an immune modulating diet (Stresson-Group A) or an isonitrogenous, isocaloric feed (1250 Calories and 75 g protein/l--Nutrison High Protein-Group B) for 10-15 days. Feeding was commenced 4h postoperatively and continued for 20 h/day. The target volume (ml/h) was 25 on day 0, 50 on day 1, and 75 thereafter. Outcome measures included complications, hospital stay and mortality. RESULTS A total of 108 patients (54 in each group) were analysed. Feed delivery, although less than targeted, was similar in both groups. There were 6 (11%) deaths in each group. Median (IQR) postoperative hospital stay was 14.5 (12-23) days in Group A and 17.5 (13-23) days in Group B (P=0.48). A total of 24 (44%) patients in each group had infective complications (P=1.0). A total of 21 (39%) patients in Group A and 28 (52%) in Group B had non-infective complications (P=0.18). Jejunostomy-related complications occurred in 26 (48%) patients in Group A and 30 (56%) in Group B (P=0.3). CONCLUSION Early postoperative feeding with an immune modulating diet conferred no outcome advantage when compared with a standard feed.
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Affiliation(s)
- Dileep N Lobo
- Section of Surgery, University Hospital, Queen's Medical Centre, E Floor, West Block, Nottingham NG7 2UH, UK.
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Hubert-Buron A, Leblond J, Jacquot A, Ducrotté P, Déchelotte P, Coëffier M. Glutamine pretreatment reduces IL-8 production in human intestinal epithelial cells by limiting IkappaBalpha ubiquitination. J Nutr 2006; 136:1461-5. [PMID: 16702304 DOI: 10.1093/jn/136.6.1461] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Glutamine, the most abundant amino acid in the human body, plays several important roles in the intestine. Recent studies showed that glutamine regulates protein metabolism and intestinal inflammation among other mechanisms by reducing proinflammatory cytokine release. Because regulation of the inflammatory response was shown to be linked to proteolysis regulation, we hypothesized that glutamine pretreatment could act on IL-8 production in human intestinal epithelial cells through the regulation of inhibitor kappaB (IkappaB) ubiquitination. The HCT-8 cells were pretreated for 24 h with 0.6, 2, or 10 mmol/L glutamine. IL-8 concentration and IkappaB (free and ubiquitinated) expressions were assessed by ELISA and immunoblotting, respectively. A pretreatment with 10 mmol/L glutamine decreased IL-8 production under both basal and proinflammatory conditions (both P < 0.05). In the presence of a proteasome inhibitor (MG132), the ubiquitin-IkappaBalpha complex expression was not significantly modified by glutamine under basal conditions but decreased significantly under proinflammatory conditions (P < 0.05). After the addition of 10 mmol/L of glutamine, the free IkappaBalpha expression increased under basal and stimulated conditions (both P < 0.05). A glutamine pretreatment of 10 mmol/L did not affect ubiquitin expression or proteasome activity. This study indicates that glutamine pretreatment may reduce the intestinal inflammatory response by limiting the proteolysis of IkappaBalpha.
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Affiliation(s)
- Aurélie Hubert-Buron
- Appareil Digestif Environnement et Nutrition (ADEN EA-3234), Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, Medical Faculty, Rouen, France
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Yeh CL, Hsu CS, Chen SC, Pai MH, Yeh SL. EFFECT OF GLUTAMINE ON CELLULAR ADHESION MOLECULE EXPRESSION AND LEUKOCYTE TRANSMIGRATION IN ENDOTHELIAL CELLS STIMULATED BY PLASMA OR PERITONEAL DRAIN FLUID FROM A SURGICAL PATIENT. Shock 2006; 25:236-40. [PMID: 16552354 DOI: 10.1097/01.shk.0000192120.45425.54] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
This study investigated the effect of glutamine (GLN) concentration on surface molecule expression on endothelial cells (ECs) and leukocytes and the transendothelial migration of polymorphonuclear neutrophils (PMNs) through ECs stimulated by plasma or peritoneal drain fluid (PDF) from a surgical patient. Human umbilical vein ECs (HUVECs) and PMNs from normal subjects were treated with different concentrations (0, 300, 600, and 1000 micromol/L) of GLN for 24 h. After that, HUVECs were stimulated for 3 h with plasma or PDF from a patient who had undergone abdominal surgery, and PMNs were allowed to transmigrate through ECs for 2 h. HUVEC surface expression of cell adhesion molecules and integrin (CD11b) and interleukin (IL) 8 receptor expression on PMNs were measured by flow cytometry. PMNs transmigrating through ECs were also analyzed. The results showed that cell adhesion molecule and integrin expressions in PDF groups were higher than those in control groups. Among the PDF groups, cellular adhesion molecule expressions on ECs and CD11b expression on PMNs were lower with 600 and 1000 micromol/L than with 300 micromol/L GLN. IL-8 secretions from ECs and PMNs were higher with 300 and 600 micromol/L than with 1000 micromol/L GLN, and this was consistent with the expression of the IL-8 receptor on PMNs. PMN transmigration was significantly higher with 300 micromol/L GLN than with the other GLN concentrations. HUVECs stimulated by plasma from surgical patient had the similar effects on surface molecule expression as PDF; however, the influences were not so obvious as shown in PDF stimulation. The results of this in vitro study suggest that ECs and PMNs were activated after patient's plasma or PDF stimulation. A low GLN concentration comparable to catabolic conditions resulted in higher adhesion molecule expression and greater transendothelial migration of neutrophils. GLN administration at levels similar to or higher than physiological concentrations reduced IL-8 and adhesion molecule expression, and PMN transmigration was also decreased after stimulation with plasma or PDF from a surgical patient.
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Affiliation(s)
- Chiu-Li Yeh
- Graduate Institute of Pharmacy, Taipei Medical University, Taipei, Taiwan
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Hou YC, Hsu CS, Yeh CL, Chiu WC, Pai MH, Yeh SL. Effects of glutamine on adhesion molecule expression and leukocyte transmigration in endothelial cells exposed to arsenic. J Nutr Biochem 2005; 16:700-4. [PMID: 16084078 DOI: 10.1016/j.jnutbio.2005.04.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2005] [Revised: 04/22/2005] [Accepted: 04/22/2005] [Indexed: 11/16/2022]
Abstract
This study evaluated whether glutamine (GLN) concentration was related to endothelial surface molecule expression and the migration of polymorphonuclear neutrophils (PMNs) through endothelial cells (ECs) stimulated by arsenic. Human umbilical vein endothelial cells (HUVECs) and PMNs were treated with different GLN concentrations (0, 300, 600 and 1000 microM) for 24 h. After that, we stimulated HUVECs for 3 h with 0.5 microM arsenic, and PMNs were allowed to transmigrate to ECs for 2 h. HUVEC surface expressions of cell adhesion molecules and integrin (CD11b) and interleukin (IL)-8 receptor expressions on PMNs were measured. The transendothelial migration of PMNs was also analyzed. The results showed that cell adhesion molecule (CAM) and integrin expressions in arsenic groups were higher than in those without arsenic. Among the arsenic groups, the expression of CAMs on ECs and CD11b, and IL-8 receptor on PMNs was lowest with 0 microM compared with the other GLN concentrations. Vascular CAM-1 on ECs and CD11b on PMN expression were higher with 300 microM than with 600 and 1000 microM GLN. IL-8 secretions from ECs and PMNs were higher with 300 muM than with 600 and 1000 microM GLN, and this was consistent with the expression of the IL-8 receptor on PMNs. Polymorphonuclear neutrophil transmigration was significantly higher with 300 muM GLN than with other GLN concentrations. These results suggest that ECs and PMNs were activated after arsenic stimulation. Cell adhesion molecule expressions on ECs and PMNs were suppressed in the absence of GLN. A low GLN concentration comparable to catabolic conditions resulted in higher adhesion molecule expression and greater transendothelial migration of neutrophils. Glutamine administration at levels similar to or higher than physiological concentrations reduced IL-8 and adhesion molecule expression; PMN transmigration was also decreased after stimulation with arsenic.
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Affiliation(s)
- Yu-Chen Hou
- Institute of Nutrition and Health Sciences, Taipei Medical University, Taiwan, ROC
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Marion R, Coëffier M, Lemoulan S, Gargala G, Ducrotté P, Déchelotte P. L-Arginine modulates CXC chemokines in the human intestinal epithelial cell line HCT-8 by the NO pathway. Biochimie 2005; 87:1048-55. [PMID: 16040184 DOI: 10.1016/j.biochi.2005.06.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2005] [Accepted: 06/17/2005] [Indexed: 12/23/2022]
Abstract
Arginine has immunomodulating properties in different animal models but its effects in human intestine remain unknown. This study examined whether arginine modulates inflammatory mediators as chemokines and nitric oxide (NO) in the human intestinal epithelial cell line HCT-8 induced by cytokines. Under basal conditions, arginine did not influence iNOS protein expression, NO and chemokine production and mRNA levels (P>0.05 for all). Stimulation with cytokines-induced a significant increase of NO and chemokine production, iNOS and chemokine mRNA level and iNOS protein expression. Under inflammatory conditions, arginine increased 30% NO production (P<0.05) but did not influence iNOS mRNA level or iNOS protein expression. Under stimulated conditions, arginine decreased IL-8 and Mig mRNA level (57% and 39%, for 0.1 vs. 2 mmol/l l-arginine, P<0.05, respectively), and production (respectively, 28 and 23%, both P<0.05). IP-10 and I-TAC mRNA level and production were not significantly influenced by arginine. Under inflammatory conditions, l-arginine as well as a NO donor (sodium nitroprusside (SNP)) increased NO production, which was inversely correlated with IL-8 production (r'=-0.66, P=0.007 for arginine; r'=-0.79, P<0.0001 for SNP). Use of NG-Methyl-l-arginine acetate, a NOS inhibitor which prevents arginine-induced NO production, suppressed the arginine-induced IL-8 inhibition (P<0.05). In HCT-8 cells, arginine enhanced cytokine-induced NO production, reduced IL-8 and Mig production and mRNA level and had no effects on other assessed chemokines. In conclusion, arginine-induced IL-8 inhibition in HCT-8 cells involves NO pathway under inflammatory conditions. These data suggest that arginine-enriched enteral nutrition may have significant influence on inflammatory response in human intestine.
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Affiliation(s)
- Rachel Marion
- Appareil Digestif Environnement Nutrition (ADEN EA 3234), Faculté de Médecine-Pharmacie, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (I.F.R. 23), 22, boulevard Gambetta, 76183 Rouen cedex, France
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Hsu CS, Chou SY, Liang SJ, Chang CY, Yeh CL, Yeh SL. Effect of glutamine on cell adhesion molecule expression and leukocyte transmigration in endothelial cells stimulated by preeclamptic plasma. Nutrition 2005; 21:1134-40. [PMID: 16308137 DOI: 10.1016/j.nut.2005.04.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2005] [Accepted: 04/21/2005] [Indexed: 02/07/2023]
Abstract
OBJECTIVE This study analyzed plasma glutamine (GLN) concentrations in women with preeclampsia. Also, in an in vitro study we evaluated whether GLN concentration was related to surface molecule expressions on endothelial cells (ECs) and polymorphonuclear neutrophils (PMNs) and the transendothelial migration of PMNs through ECs stimulated by preeclamptic plasma. METHODS Blood samples were collected from 20 women with preeclampsia and 15 normal pregnant women for plasma GLN analysis. In the in vitro study, human umbilical vein endothelial cells and PMNs were treated with different concentrations (0, 300, 500, and 1000 microM) of GLN for 24 h. After that, we stimulated human umbilical vein endothelial cells for 3 h with plasma from patients with preeclampsia, and PMNs were allowed to transmigrate through ECs for 2 h. EC surface expressions of cellular adhesion molecules (CAMs) and integrin (CD11b) interleukin-8 (IL-8) receptor expressions on PMNs were measured by flow cytometry. The transendothelial migration of PMNs through ECs was also analyzed. RESULTS Women with preeclampsia exhibited significantly lower plasma GLN concentrations than did normal pregnant women. The in vitro study showed that, compared with normal plasma, CAM expressions on human umbilical vein endothelial cells and PMNs were increased when preeclamptic plasma was stimulated. Among the groups with preeclamptic plasma stimulation, intracellular CAM-1 expression on ECs and CD11b and IL-8 receptor expressions on PMNs were lower with 500 and 1000 microM than with 300 microM of GLN. IL-8 production from ECs and PMNs was also lower with 500 and 1000 microM than with 300 microM of GLN. PMN transmigration was significantly higher with 300 microM of GLN than with the other GLN concentrations. CONCLUSIONS Plasma GLN is depleted in women with preeclampsia. The result of this in vitro study showed that ECs and PMNs were activated after preeclamptic plasma stimulation. A low GLN concentration resulted in greater CAM expression and greater transendothelial migration of neutrophils. GLN administration at levels similar to or higher than physiologic concentrations decreased IL-8 and CAM expressions, and PMN transmigration decreased after stimulation with preeclamptic plasma.
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Affiliation(s)
- Chun-Sen Hsu
- Department of Obstetrics and Gynecology, Taipei Medical University Municipal Wan Fang Hospital, Taiwan, Republic of China
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Lecleire S, Coeffier M, Leblond J, Hubert A, Lemoulan S, Petit A, Ducrotte P, Dechelotte P, Marion R. Modulation of nitric oxide and cytokines production by l-arginine in human gut mucosa. Clin Nutr 2005; 24:353-9. [PMID: 15896421 DOI: 10.1016/j.clnu.2004.11.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2004] [Accepted: 11/29/2004] [Indexed: 11/20/2022]
Abstract
BACKGROUND Arginine is a conditionally essential amino-acid with immuno-modulatory properties, mainly through the nitric oxide (NO) pathway. AIM To assess the effects of arginine on intestinal production of pro- and anti-inflammatory cytokines and NO in human gut. METHODS An enteral solution of arginine or a control solution of amino-acids was administered to 8 healthy volunteers on a randomized cross-over design. Duodenal biopsies were taken. Pro- (IL-6, IL-8) and anti-inflammatory (IL-4, IL-10) cytokines mRNA expression was assessed by RT-PCR. Other biopsies were cultured with 0.1, 0.5 or 2 mM arginine or control amino-acids, under basal or IL-1beta-induced inflammatory conditions. Interleukin-4, IL-6, IL-8 and IL-10 production was measured in culture supernatant by ELISA and NO production by Griess reaction. RESULTS Arginine enhanced the production of NO under inflammatory conditions in a dose-dependent manner (P=0.03). IL-1beta increased the production of IL-8 and IL-6 (P<0.01). Arginine had no effect on pro- and anti-inflammatory cytokines production both under basal and inflammatory conditions. CONCLUSIONS Arginine enhanced the production of NO but did not affect that of cytokines in inflammatory human gut. Further clinical studies are required to assess whether arginine-enhanced NO production plays a beneficial or deleterious effect in intestinal inflammation.
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Affiliation(s)
- Stephane Lecleire
- Appareil Digestif Environnement Nutrition (ADEN EA 3234) and Institut Fédératif de Recherches Multidisciplinaires sur les peptides (IFR n 23), CIC-INSERM-CHU, 76031 Rouen Cedex, France.
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Coëffier M, Déchelotte P. The role of glutamine in intensive care unit patients: mechanisms of action and clinical outcome. Nutr Rev 2005; 63:65-9. [PMID: 15762090 DOI: 10.1111/j.1753-4887.2005.tb00123.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Patients in the intensive care unit are at high risk of glutamine depletion and subsequent complications. Several controlled studies and a meta-analysis have concluded that glutamine supplementation has beneficial effects on the clinical outcome of critically ill and surgical patients. These results may be explained by glutamine's influences on the inflammatory response, oxidative stress, cell protection, and the gut barrier. In addition, glutamine may also improve glucose metabolism by reducing insulin resistance.
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Affiliation(s)
- Moïse Coëffier
- Appareil Digestif Environnement Nutrition, IFR 23, Faculté de Médecine-Pharmacie, Rouen, France
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Liboni KC, Li N, Scumpia PO, Neu J. Glutamine modulates LPS-induced IL-8 production through IkappaB/NF-kappaB in human fetal and adult intestinal epithelium. J Nutr 2005; 135:245-51. [PMID: 15671221 DOI: 10.1093/jn/135.2.245] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The intestinal epithelium may serve as a nidus for inflammation that can cause local and systemic organ dysfunction. Relative to the adult, the immature intestine is exquisitely sensitive to inflammatory agents. Glutamine (Gln), an amino acid that is rapidly depleted during critical illness, modulates intestinal inflammation in vitro and in vivo. Here we relate Gln status to activation of the inhibitor of kappaB (IkappaB)/nuclear factor (NF)-kappaB signaling pathway in fetal-derived (H4) and adult (Caco-2) enterocytes. In the absence of Gln with or without LPS, H4 cells expressed more interleukin (IL)-8) than Caco-2 cells. Gln supplementation partially prevented the LPS-induced elevation of IL-8 in both cell types. IkappaBalpha was significantly decreased in both H4 and Caco-2 cells with Gln deprivation, and this was followed by an increase in NF-kappaB p65 in the nucleus. DNA binding of NF-kappaB was increased in both H4 and Caco-2 cells with Gln deprivation. IkappaBalpha phosphorylation was not altered by Gln status in either H4 or Caco-2 cells. Proteasomal inhibition after Gln depletion in Caco-2 cells was associated with an increase in the IkappaB-ubiquitin complex, but a decrease in complex formation in H4 cells, indicating that Gln deprivation alters IkappaBalpha through a pathway that differs from Caco-2 cells. We speculate that a reduced capacity of the immature enterocyte (H4) to respond to Gln deprivation with increased synthesis of IkappaBalpha rather than increased proteolysis as seen in the Caco-2 cells is the underlying mechanism.
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Affiliation(s)
- Kellym C Liboni
- Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610-0296, USA
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Marion R, Coëffier MM, Gargala G, Ducrotté P, Déchelotte PP. Glutamine and CXC chemokines IL-8, Mig, IP-10 and I-TAC in human intestinal epithelial cells. Clin Nutr 2004; 23:579-85. [PMID: 15297094 DOI: 10.1016/j.clnu.2003.10.011] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2003] [Accepted: 10/15/2003] [Indexed: 01/06/2023]
Abstract
BACKGROUNDS & AIMS Chemokines are a family of small proteins involved in immune and inflammatory responses. Human intestinal epithelial cells act as a sentinel in the immune response and produce CXC chemokines such as IL-8, Mig, IP-10 and I-TAC. Glutamine has various effects on immuno-inflammatory response in human intestine. METHODS The present study aimed to determine the effect of glutamine on the IL-8, Mig, IP-10 and I-TAC production by ELISA and their mRNA level by RT-PCR (expressed as % gapdh) in two human intestinal epithelial cell lines Caco-2/TC7 and HCT-8 under basal conditions or during stimulation with combined cytokines. RESULTS Under basal conditions, studied chemokines were not influenced by glutamine. When intestinal epithelial cells were stimulated with cytokines, increasing concentrations of glutamine from 2 to 10 mM in HCT-8 cells significantly decreased I-TAC and IP-10 mRNA level (respectively 219 to 182%; P < 0.01; 257 to 176%; P < 0.05) and I-TAC and IP-10 production (respectively 21.2 to 13.0; P < 0.05; 696 to 548 ng/prot mg; P < 0.01). Glutamine also reduced IP-10 mRNA level (186 to 135%, P < 0.05) in cytokines-stimulated Caco-2/TC7 cells. CONCLUSIONS Down-regulation of CXC chemokines by glutamine could contribute to its therapeutic potential in intestinal inflammation and during critical illness.
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Affiliation(s)
- Rachel Marion
- Appareil Digestif Environnement Nutrition (ADEN EA 3234), Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (I.F.R.23), Rouen, France
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Li N, Lassman BJ, Liu Z, Liboni K, Neu J. Effects of protein deprivation on growth and small intestine morphology are not improved by glutamine or glutamate in gastrostomy-fed rat pups. J Pediatr Gastroenterol Nutr 2004; 39:28-33. [PMID: 15187776 DOI: 10.1097/00005176-200407000-00006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Critically ill neonates often have their enteral intake severely limited shortly after birth. Whether glutamine (Gln) or glutamate (Glu) can preserve intestinal structure and function in the neonate undergoing limited enteral feeding is not clear. We hypothesize that Gln and Glu can similarly preserve intestinal structure in the developing small intestine of infant rats fed a low protein diet. METHODS Using a gastrostomy-fed "pup-in-a-cup" rat model, the effects of Gln and Glu on the developing rat small intestine were examined. Four groups of 6- to 7-day-old pups were fed rat milk substitute (RMS) via gastrostomy tube. One group was provided 100% and three were provided 25% of the protein normally received from their mothers. Two of the groups fed 25% protein received additional Gln or Glu for 6 days. RESULTS Pups receiving the 100% protein RMS were larger than pups receiving the 25% protein RMS with or without Gln/Glu supplementation (P < 0.001). Average villus height (P < 0.01) and area (P < 0.01) were greater in pups receiving 100% protein RMS than in pups given 25% protein RMS formula. There was no significant difference among the groups in mucosal maltase or alkaline phosphatase activities. Tight junction protein claudin-1 was significantly higher in the group fed 100% protein RMS diet, while occludin did not differ among the 4 groups. Neither Gln nor Glu increased claudin-1 or occludin in rats fed 25% protein. CONCLUSIONS These results suggest that neither Gln nor Glu supplementation can substitute effectively for whole protein in the developing rat small intestine for the outcomes that were evaluated.
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Affiliation(s)
- Nan Li
- Department of Pediatrics, University of Florida, College of Medicine, Gainesville, Florida, USA
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Li N, Liboni K, Fang MZ, Samuelson D, Lewis P, Patel R, Neu J. Glutamine decreases lipopolysaccharide-induced intestinal inflammation in infant rats. Am J Physiol Gastrointest Liver Physiol 2004; 286:G914-21. [PMID: 14726310 DOI: 10.1152/ajpgi.00493.2003] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Using a gastrostomy-fed (GF) rat infant "pup-in-a-cup" model, the effects of protein deprivation and supplemental glutamine (Gln) and glutamate (Glu) were examined to test the hypothesis that Gln decreases the proinflammatory response induced by LPS in the developing infant rat small intestine. Four groups of 6- to 7-day-old pups were fed a rat milk substitute (RMS), one providing 100% and three providing 25% of normal protein intake for another 6 days. Two of the 25% protein-fed groups received supplemental Gln or Glu. GF and LPS treatment blunted body growth and intestinal villus height and increased intestinal cytokine-induced neutrophil chemoattractant (CINC) mRNA in the protein-deprived, non-Gln-treated group compared with mother-fed pups (P < 0.05). Gln blunted intestinal CINC mRNA (P < 0.05), but Glu did not. Intestinal CINC peptide in the LPS-treated pups provided 100 and 25% protein was elevated approximately 13-fold compared with the mother-reared pups (P < 0.001). Gln and Glu decreased intestinal CINC peptide by 73 and 80%, respectively. GF, LPS-treated pups also had a higher level of plasma CINC peptide (P < 0.05). Gln but not Glu decreased plasma CINC peptide (P < 0.05). An approximate sixfold elevation of intestinal MPO activity in the GF, LPS-treated rats was decreased by Gln and Glu by 92% (P < 0.001) and 54% (P < 0.05), respectively. Intestinal and plasma TNF-alpha were increased in GF, LPS-treated pups (P < 0.01), and Gln and Glu both blunted this increase (P < 0.05) in the intestine but not in the plasma. The results indicate that Gln decreases the LPS-induced inflammatory response in infant rat intestine under different conditions of protein intake.
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Affiliation(s)
- Nan Li
- Department of Pediatrics, University of Florida, College of Medicine, Gainesville, FL 32610, USA
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Fürst P, Alteheld B, Stehle P. Why should a single nutrient—glutamine—improve outcome? ACTA ACUST UNITED AC 2004. [DOI: 10.1016/j.clnu.2004.07.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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