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Varasteh S, Braber S, Kraneveld AD, Garssen J, Fink-Gremmels J. l-Arginine supplementation prevents intestinal epithelial barrier breakdown under heat stress conditions by promoting nitric oxide synthesis. Nutr Res 2018; 57:45-55. [DOI: 10.1016/j.nutres.2018.05.007] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Revised: 05/03/2018] [Accepted: 05/31/2018] [Indexed: 01/01/2023]
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Liu C, Zuo Z, Zhu P, Zheng Z, Peng X, Fang J, Cui H, Zhou Y, Ouyang P, Geng Y, Deng J, Sun Y. Sodium selenite prevents suppression of mucosal humoral response by AFB 1 in broiler's cecal tonsil. Oncotarget 2017; 8:54215-54226. [PMID: 28903335 PMCID: PMC5589574 DOI: 10.18632/oncotarget.17105] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 04/02/2017] [Indexed: 12/26/2022] Open
Abstract
Aflatoxin B1 (AFB1), the most common mycotoxin in human food and animal feed, produces hepatotoxic, genotoxic and immunosuppressive effects in multiple species. Selenium (Se) has emerged as an important element in the dietary prevention of various toxic agents. The present study was designed to scrutinize the protective effects of sodium selenite on the histological lesions and suppression of mucosal humoral response in the cecal tonsil generated by AFB1. A total of 156 one-day-old broilers were divided into four groups and fed on basal diet (control group), 0.6 mg/kg AFB1 (AFB1 group), 0.4 mg/kg Se supplement (+Se group), and 0.6 mg/kg AFB1 + 0.4 mg/kg Se supplement (AFB1+Se group) respectively for 21 days. Our results showed that 0.4 mg/kg Se supplement in broiler's diets could improve the AFB1-induced histological lesions in the cecal tonsils including the depletion of lymphocytes in the lymphatic nodules as well as the shedding of microvilli in the absorptive cells. Moreover, Se could restore the decreased number of IgA+ cells and expression levels of pIgR, IgA, IgG, and IgM mRNA induced by AFB1 to be close to those in the control group. These results demonstrated that 0.4 mg/kg supplemented dietary Se in the form of sodium selenite could protect the cecal tonsils from the histological lesions and suppression of the mucosal humoral response provoked by 0.6 mg/kg AFB1. Our study may provide new experimental evidences for better understanding of AFB1-induced damage of mucosal immunity and protective effect of Se against this toxin.
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Affiliation(s)
- Chunyu Liu
- Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China.,College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Zhicai Zuo
- Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China.,College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Panpan Zhu
- Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China.,College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Zhixiang Zheng
- Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China.,College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Xi Peng
- College of Life Sciences, China West Normal University, Nanchong, Sichuan, PR China
| | - Jing Fang
- Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China.,College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Hengmin Cui
- Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China.,College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Yi Zhou
- Life Science Department, Sichuan Agricultural University, Yaan, Sichuan, PR China
| | - Ping Ouyang
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Yi Geng
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Junliang Deng
- Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China.,College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Yu Sun
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China
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Huang L, Ma XY, Jiang ZY, Hu YJ, Zheng CT, Yang XF, Wang L, Gao KG. Effects of soybean isoflavone on intestinal antioxidant capacity and cytokines in young piglets fed oxidized fish oil. J Zhejiang Univ Sci B 2016; 17:965-974. [PMID: 27921401 PMCID: PMC5172600 DOI: 10.1631/jzus.b1600078] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2016] [Accepted: 05/04/2016] [Indexed: 01/29/2023]
Abstract
To investigate the effect of glycitein, a synthetic soybean isoflavone (ISF), on the intestinal antioxidant capacity, morphology, and cytokine content in young piglets fed oxidized fish oil, 72 4-d-old male piglets were assigned to three treatments. The control group was fed a basal diet containing fresh fish oil, and the other two groups received the same diet except for the substitution with the same dosage of oxidized fish oil alone or with ISF (oxidized fish oil plus ISF). After 21 d of feeding, supplementation of oxidized fish oil increased the levels of malondialdehyde (MDA), oxidized glutathione (GSSG), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), nuclear factor κ B (NF-κB), inducible nitric oxide synthase (iNOS), NO, and Caspase-3 in jejunal mucosa, and decreased the villous height in duodenum and the levels of secretory immunoglobulin A (sIgA) and IL-4 in the jejunal mucosa compared with supplementation with fresh oil. The addition of oxidized fish oil plus ISF partially alleviated this negative effect. The addition of oxidized fish oil plus ISF increased the villous height and levels of sIgA and IL-4 in jejunal mucosa, but decreased the levels of IL-1β and IL-2 in jejunal mucosa (P<0.05) compared with oxidized fish oil. Collectively, these results show that dietary supplementation of ISF could partly alleviate the negative effect of oxidized fish oil by improving the intestinal morphology as well as the antioxidant capacity and immune function in young piglets.
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Wu B, Cui H, Peng X, Fang J, Zuo Z, Deng J, Wang X, Huang J. Toxicological effects of nickel chloride on the cytokine mRNA expression and protein levels in intestinal mucosal immunity of broilers. ENVIRONMENTAL TOXICOLOGY 2015; 30:1309-1321. [PMID: 24801245 DOI: 10.1002/tox.22001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2014] [Revised: 04/18/2014] [Accepted: 04/25/2014] [Indexed: 06/03/2023]
Abstract
The purpose of this study was to examine the toxicological effects of nickel chloride (NiCl2 ; 300, 600, and 900 mg kg(-1) diet) on the cytokine mRNA expression and protein levels in the intestinal mucosa and cecal tonsil, and on the ileac and cecal tonsil T cells in broilers by the methods of qRT-PCR, flow cytometry and ELISA for 42 days. Results showed that the IL-2, IL-6, IL-10, IL-17, IFN-γ, and TNF-α (LITAF) cytokine mRNA expression and protein levels were lower (P < 0.05 or P < 0.01) and the percentages of T-cell subsets were also lower in the 300, 600, and 900 mg kg(-1) groups than in the control group. It was concluded that dietary NiCl2 in excess of 300 mg kg(-1) could reduce cytokine mRNA expression and protein levels in the intestinal mucosa and cecal tonsil, and the percentages of ileac and cecal tonsil T-cell subsets. Decreasing in cytokine mRNA expression and protein levels of intestinal mucosa and cecal tonsil induced by NiCl2 was closely related to the reduction of T-cell population. Thus, the abnormal expression of these cytokines impacts the intestinal mucosal immune function by the pathways of reducing of lymphocyte population and activation. Also, this study first proved that NiCl2 at higher levels has the toxicological effects on intestinal mucosal immunity.
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Affiliation(s)
- Bangyuan Wu
- Department of Animal Diseases and Environmental Hazards, Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan, China
| | - Hengmin Cui
- Department of Animal Diseases and Environmental Hazards, Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan, China
- College of Veterinary Medicine, Sichuan Agricultural University, Ya'an, 625014, China
| | - Xi Peng
- Department of Animal Diseases and Environmental Hazards, Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan, China
- College of Veterinary Medicine, Sichuan Agricultural University, Ya'an, 625014, China
| | - Jing Fang
- Department of Animal Diseases and Environmental Hazards, Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan, China
- College of Veterinary Medicine, Sichuan Agricultural University, Ya'an, 625014, China
| | - Zhicai Zuo
- Department of Animal Diseases and Environmental Hazards, Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan, China
- College of Veterinary Medicine, Sichuan Agricultural University, Ya'an, 625014, China
| | - Junliang Deng
- Department of Animal Diseases and Environmental Hazards, Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan, China
- College of Veterinary Medicine, Sichuan Agricultural University, Ya'an, 625014, China
| | - Xun Wang
- College of Animal Science and Technology, Sichuan Agricultural University, Ya'an, 625014, China
| | - Jianying Huang
- Department of Animal Diseases and Environmental Hazards, Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan, China
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Jiang M, Fang J, Peng X, Cui H, Yu Z. Effect of aflatoxin B₁ on IgA⁺ cell number and immunoglobulin mRNA expression in the intestine of broilers. Immunopharmacol Immunotoxicol 2015; 37:450-7. [PMID: 26357012 DOI: 10.3109/08923973.2015.1081933] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Aflatoxin B1 (AFB1) is the most toxic group of mycotoxins produced by two species of the Aspergillus, common contaminants of food and animal feed. The purpose of our study was to determine the effect of AFB1 on the number of IgA(+) cell and immunoglobulin mRNA expression in the intestine of broilers. One hundred and fifty six one-day-old healthy Cobb broilers were randomly divided into the control group (the dosage of 0 mg/kg AFB1) and AFB1 group (the dosage of 0.6 mg/kg AFB1) with three replicates per group and 26 birds per replicate for 21 days, respectively. After necropsy at 7, 14 and 21 days of age, duodenum, jejunum and ileum samples were taken for analyzing IgA(+) cell by immunohistochemistry and IgA, pIgR, IgM and IgG mRNA expression by qRT-PCR. IgA(+) cells were mainly distributed in the lamina propria of small intestinal mucosa in both groups at 14 and 21 days of age. A significant decrease in the number of IgA(+) cells in the duodenum, jejunum and ileum was revealed in the AFB1 group compared with that of the control group. The expression levels of IgA, pIgR, IgM and IgG mRNA in the intestinal mucosa were lower in the AFB1 group than those in the control group at 14 and 21 days of age. Our data demonstrated that the dosage of 0.6 mg/kg AFB1 in broiler diet reduced the number of IgA(+) cell and the expression of IgA, pIgR, IgM and IgG mRNA in the small intestine.
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Affiliation(s)
- Min Jiang
- a Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University , Ya'an , Sichuan , P.R. China
| | - Jing Fang
- a Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University , Ya'an , Sichuan , P.R. China
| | - Xi Peng
- a Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University , Ya'an , Sichuan , P.R. China
| | - Hengmin Cui
- a Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University , Ya'an , Sichuan , P.R. China
| | - Zhengqiang Yu
- a Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University , Ya'an , Sichuan , P.R. China
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Abstract
Glucagon-like peptide-2 (GLP-2) is a single chain polypeptide hormone with a molecular weight of 3.9 kDa, which is secreted by L cells of the intestine. GLP-2 is a specific intestinal epithelial growth factor, and it can promote the repair of intestinal mucosa injury, inhibit apoptosis, improve the intestinal absorption of nutrients, and strengthen the intestinal barrier function. GLP-2 also plays an important role in maintaining the continuity and integrity of the intestinal mucosa. These characteristics make GLP-2 become the current research hotspot in the field of gastrointestinal barrier function. The main focus of previous studies is on nutrient absorption and protection of the intestinal mechanical barrier, and there have been relatively scarce studies on the protective effect of GLP-2 on intestinal mucosal immune barrier. This article reviews the role of GLP-2 in intestinal mucosal immunity and the possible mechanisms.
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Badurdeen S, Mulongo M, Berkley JA. Arginine depletion increases susceptibility to serious infections in preterm newborns. Pediatr Res 2015; 77:290-7. [PMID: 25360828 PMCID: PMC4335378 DOI: 10.1038/pr.2014.177] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Accepted: 09/02/2014] [Indexed: 12/21/2022]
Abstract
Preterm newborns are highly susceptible to bacterial infections. This susceptibility is regarded as being due to immaturity of multiple pathways of the immune system. However, it is unclear whether a mechanism that unifies these different, suppressed pathways exists. Here, we argue that the immune vulnerability of the preterm neonate is critically related to arginine depletion. Arginine, a "conditionally essential" amino acid, is depleted in acute catabolic states, including sepsis. Its metabolism is highly compartmentalized and regulated, including by arginase-mediated hydrolysis. Recent data suggest that arginase II-mediated arginine depletion is essential for the innate immune suppression that occurs in newborn models of bacterial challenge, impairing pathways critical for the immune response. Evidence that arginine depletion mediates protection from immune activation during first gut colonization suggests a regulatory role in controlling gut-derived pathogens. Clinical studies show that plasma arginine is depleted during sepsis. In keeping with animal studies, small clinical trials of L-arginine supplementation have shown benefit in reducing necrotizing enterocolitis in premature neonates. We propose a novel, broader hypothesis that arginine depletion during bacterial challenge is a key factor limiting the neonate's ability to mount an adequate immune response, contributing to the increased susceptibility to infections, particularly with respect to gut-derived sepsis.
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Affiliation(s)
- Shiraz Badurdeen
- Department of Paediatrics, Oxford University Hospitals NHS Trust, Oxford, UK,()
| | - Musa Mulongo
- KEMRI-Wellcome Trust, Centre for Geographic Medicine and Research-Coast, Kilifi, Kenya
| | - James A. Berkley
- KEMRI-Wellcome Trust, Centre for Geographic Medicine and Research-Coast, Kilifi, Kenya,Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
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Supplemental dietary L-arginine attenuates intestinal mucosal disruption during a coccidial vaccine challenge in broiler chickens. Br J Nutr 2014; 112:1098-109. [PMID: 25181320 DOI: 10.1017/s0007114514001846] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The present study investigated the effects of dietary arginine (Arg) supplementation on intestinal structure and functionality in broiler chickens subjected to coccidial challenge. The present study was a randomised complete block design employing a 3 × 2 factorial arrangement (n 8) with three dietary concentrations of Arg (11·1, 13·3 and 20·2 g/kg) with or without coccidial vaccine challenge (unchallenged and coccidial challenge). On day 14, birds were orally administered with coccidial vaccine or saline. On day 21, birds were killed to obtain jejunal tissue and mucosal samples for histological, gene expression and mucosal immunity measurements. Within 7 d of the challenge, there was a decrease in body-weight gain and feed intake, and an increase in the feed:gain ratio (P< 0·05). Jejunal inflammation was evidenced by villus damage, crypt dilation and goblet cell depletion. Coccidial challenge increased mucosal secretory IgA concentration and inflammatory gene (iNOS, IL-1β, IL-8 and MyD88) mRNA expression levels (P< 0·05), as well as reduced jejunal Mucin-2, IgA and IL-1RI mRNA expression levels (P< 0·05). Increasing Arg concentration (1) increased jejunal villus height (P< 0·05) and linearly increased jejunal crypt depth (P< 0·05); (2) quadratically increased mucosal maltase activity (P< 0·05) and linearly decreased mucosal secretory IgG concentration (P< 0·05) within the coccidiosis-challenged groups; and (3) linearly decreased jejunal Toll-like receptor 4 (TLR4) mRNA expression level (P< 0·05) within the coccidiosis-challenged groups. The mRNA expression of mechanistic target of rapamycin (mTOR) complex 1 pathway genes (mTOR and RPS6KB1) and the anti-apoptosis gene Bcl-2 quadratically responded to increasing dietary Arg supplementation (P< 0·05). These results indicate that dietary Arg supplementation attenuates intestinal mucosal disruption in coccidiosis-challenged chickens probably through suppressing TLR4 and activating mTOR complex 1 pathways.
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He Y, Fang J, Peng X, Cui H, Zuo Z, Deng J, Chen Z, Geng Y, Lai W, Shu G, Tang L. Effects of sodium selenite on aflatoxin B1-induced decrease of ileal IgA+ cell numbers and immunoglobulin contents in broilers. Biol Trace Elem Res 2014; 160:49-55. [PMID: 24909240 DOI: 10.1007/s12011-014-0035-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2014] [Accepted: 05/28/2014] [Indexed: 10/25/2022]
Abstract
This study was aimed to assess the protective effect of sodium selenite on the ileum mucosal immunologic injury induced by AFB1. One hundred eighty-one-day-old healthy male Avian broilers were divided into four groups of three replicates and 15 birds per replicate and fed with basal diet (control group), 0.3 mg/kg AFB1 (AFB1 group), 0.4 mg/kg Se (+Se group), and 0.3 mg/kg AFB1 + 0.4 mg/kg Se (AFB1 + Se group) respectively. The numbers of IgA(+) cells of ileum were determined by immunohistochemistry as well as the contents of sIgA, IgA, IgG, and IgM in the mucosa of ileum by ELISA. Compared with those in the control group, the numbers of IgA(+) cells as well as the sIgA, IgA, IgG, and IgM contents were decreased in the AFB1 group. However, compared with those in the AFB1 group, the numbers of IgA(+) cells as well as the sIgA, IgA, IgG, and IgM contents were increased in the AFB1 + Se group, and these data had no difference between AFB1 + Se group and control group. It was concluded that 0.3 mg/kg AFB1 could reduce the humoral immune function of the ileum mucosa, but 0.4 mg/kg supplemented dietary selenium could protect the mucosal humoral immune function from AFB1-induced impairment.
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Affiliation(s)
- Yang He
- Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an, 625014, China
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Costa KA, Soares ADN, Wanner SP, Santos RDGCD, Fernandes SOA, Martins FDS, Nicoli JR, Coimbra CC, Cardoso VN. L-arginine supplementation prevents increases in intestinal permeability and bacterial translocation in male Swiss mice subjected to physical exercise under environmental heat stress. J Nutr 2014; 144:218-23. [PMID: 24259555 DOI: 10.3945/jn.113.183186] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Dietary supplementation with l-arginine has been shown to improve the intestinal barrier in many experimental models. This study investigated the effects of arginine supplementation on the intestinal permeability and bacterial translocation (BT) induced by prolonged physical exercise under heat stress. Under anesthesia, male Swiss mice (5-wk-old) were implanted with an abdominal sensor to record their core body temperature (T(core)). After recovering from surgery, the mice were divided into 3 groups: a non-supplemented group that was fed the standard diet formulated by the American Institute of Nutrition (AIN-93G; control), a non-supplemented group that was fed the AIN-93G diet and subjected to exertional hyperthermia (H-NS), and a group supplemented with l-arginine at 2% and subjected to exertional hyperthermia (H-Arg). After 7 d of treatment, the H-NS and H-Arg mice were forced to run on a treadmill (60 min, 8 m/min) in a warm environment (34°C). The control mice remained at 24°C. Thirty min before the exercise or control trials, the mice received a diethylenetriamine pentaacetic acid (DTPA) solution labeled with technetium-99m ((99m)Tc-DTPA) or (99m)Tc-Escherichia coli by gavage to assess intestinal permeability and BT, respectively. The H-NS mice terminated the exercise with T(core) values of ∼40°C, and, 4 h later, presented a 12-fold increase in the blood uptake of (99m)Tc-DTPA and higher bacterial contents in the blood and liver than the control mice. Although supplementation with arginine did not change the exercise-induced increase in T(core), it prevented the increases in intestinal permeability and BT caused by exertional hyperthermia. Our results indicate that dietary l-arginine supplementation preserves the integrity of the intestinal epithelium during exercise under heat stress, acting through mechanisms that are independent of T(core) regulation.
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The unique role of dietary L-arginine in the acceleration of peritoneal macrophage sensitivity to bacterial endotoxin. Immunol Res 2013. [PMID: 23184235 DOI: 10.1007/s12026-012-8379-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
It is known that cells and organisms can indirectly "sense" changes in L-arginine availability via changes in the activity of various metabolic pathways. However, the mechanism(s) by which genes can be directly regulated by L-arginine in mammalian cells have not yet been elucidated. We investigated the effect of L-arginine in the in vivo model of peritoneal inflammation in mice and in vitro in RAW 264.7 macrophages. A detailed analysis of basic physiological functions and selected intracellular signaling cascades revealed that L-arginine is crucial for the acceleration of macrophage activation by bacterial lipopolysaccharide. L-arginine increased the production of reactive oxygen species, nitric oxide, release of Ca(2+), as well as inducible nitric oxide synthase expression. Interestingly, the effect of L-arginine on macrophage activation was dependent on the phosphorylation of mitogen-activated protein kinases and activity of phospholipase C. In RAW 264.7 cells, L-arginine was shown to modulate the response of macrophages toward lipopolysaccharide via the activation of G-protein-coupled receptors. According to our data, we concluded that L-arginine availability plays a key role in the initiation of intracellular signaling pathways that trigger the lipopolysaccharide-induced inflammatory responses in murine macrophages. Although macrophages are partially stimulated in the absence of extracellular L-arginine, the presence of this amino acid significantly accelerates the sensitivity of macrophages to bacterial endotoxin.
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Alshadwi A, Nadershah M, Carlson ER, Young LS, Burke PA, Daley BJ. Nutritional Considerations for Head and Neck Cancer Patients: A Review of the Literature. J Oral Maxillofac Surg 2013; 71:1853-60. [DOI: 10.1016/j.joms.2013.04.028] [Citation(s) in RCA: 105] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2013] [Revised: 04/22/2013] [Accepted: 04/25/2013] [Indexed: 12/11/2022]
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Ruth MR, Field CJ. The immune modifying effects of amino acids on gut-associated lymphoid tissue. J Anim Sci Biotechnol 2013; 4:27. [PMID: 23899038 PMCID: PMC3750756 DOI: 10.1186/2049-1891-4-27] [Citation(s) in RCA: 129] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2013] [Accepted: 07/29/2013] [Indexed: 12/11/2022] Open
Abstract
The intestine and the gut-associated lymphoid tissue (GALT) are essential components of whole body immune defense, protecting the body from foreign antigens and pathogens, while allowing tolerance to commensal bacteria and dietary antigens. The requirement for protein to support the immune system is well established. Less is known regarding the immune modifying properties of individual amino acids, particularly on the GALT. Both oral and parenteral feeding studies have established convincing evidence that not only the total protein intake, but the availability of specific dietary amino acids (in particular glutamine, glutamate, and arginine, and perhaps methionine, cysteine and threonine) are essential to optimizing the immune functions of the intestine and the proximal resident immune cells. These amino acids each have unique properties that include, maintaining the integrity, growth and function of the intestine, as well as normalizing inflammatory cytokine secretion and improving T-lymphocyte numbers, specific T cell functions, and the secretion of IgA by lamina propria cells. Our understanding of this area has come from studies that have supplemented single amino acids to a mixed protein diet and measuring the effect on specific immune parameters. Future studies should be designed using amino acid mixtures that target a number of specific functions of GALT in order to optimize immune function in domestic animals and humans during critical periods of development and various disease states.
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Affiliation(s)
- Megan R Ruth
- Department of Agricultural, Food and Nutritional Science, 4-126A Li Ka Shing Health Research Innovation Centre, University of Alberta, Edmonton, AB T6G 2E1, Canada.
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The role of l-arginine-nitric oxide pathway in bacterial translocation. Amino Acids 2013; 45:1089-96. [DOI: 10.1007/s00726-013-1558-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2013] [Accepted: 07/03/2013] [Indexed: 01/07/2023]
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15
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Luo Q, Cui H, Peng X, Fang J, Zuo Z, Deng J, Liu J, Deng Y. Intestinal IgA⁺ cell numbers as well as IgA, IgG, and IgM contents correlate with mucosal humoral immunity of broilers during supplementation with high fluorine in the diets. Biol Trace Elem Res 2013; 154:62-72. [PMID: 23740525 DOI: 10.1007/s12011-013-9713-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2013] [Accepted: 05/21/2013] [Indexed: 01/08/2023]
Abstract
Fluoride (F), a well-recognized harmful substance, is easily absorbed by the intestinal mucosa. The intestinal mucosal immune system is equipped with unique innate and adaptive defense mechanisms that provide a first line of protection against infectious agents. Meanwhile, immunoglobulins are the major secretory products of the adaptive immune system and their levels can be a strong indicator of a disease or condition. In this study, therefore, we investigated the effects of high dietary fluorine on the numbers of immunoglobulin A-positive (IgA(+)) cells in the lamina propria of intestines (duodenum, jejunum and ileum) by immunohistochemistry as well as on the contents of immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) in the mucosa of intestines (duodenum, jejunum, and ileum) by enzyme-linked immunosorbent assay (ELISA). A total of 280 1-day-old healthy avian broilers were randomly divided into four groups and fed on a corn-soybean basal diet as control diet (fluorine 22.6 mg/kg) or the same basal diet supplemented with 400, 800, and 1,200 mg/kg fluorine (high fluorine groups I, II, and III) in the form of sodium fluoride (NaF) for 42 days. The experimental data showed that the numbers of IgA(+) cells as well as the IgA, IgG, and IgM contents were significantly decreased (P < 0.01 or P < 0.05) in the high fluorine groups II and III when compared with those of the control group. It was concluded that dietary fluorine in the range of 800-1,200 mg/kg significantly reduced the numbers of the IgA(+) cells and the contents of aforementioned immunoglobulins in the intestines (duodenum, jejunum, and ileum) of broilers, which could finally impact the mucosal humoral immune function in the intestines by a way that reduces the lymphocyte population and/or lymphocyte activation.
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Affiliation(s)
- Qin Luo
- Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China
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Mohan S, Patel H, Bolinaga J, Soekamto N. AMP-activated protein kinase regulates L-arginine mediated cellular responses. Nutr Metab (Lond) 2013; 10:40. [PMID: 23718875 PMCID: PMC3680329 DOI: 10.1186/1743-7075-10-40] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2013] [Accepted: 05/25/2013] [Indexed: 12/31/2022] Open
Abstract
Background Our prior study revealed the loss in short-term L-Arginine (ARG) therapeutic efficacy after continuous exposure; resulting in tolerance development, mediated by endothelial nitric oxide synthase (eNOS) down-regulation, secondary to oxidative stress and induced glucose accumulation. However, the potential factor regulating ARG cellular response is presently unknown. Method Human umbilical vein endothelial cells were incubated with 100 μM ARG for 2 h in buffer (short-term or acute), or for 7 days in culture medium and challenged for 2 h in buffer (continuous or chronic), in the presence or absence of other agents. eNOS activity was determined by analyzing cellular nitrite/nitrate (NO2–/NO3–), and AMP-activated protein kinase (AMPK) activity was assayed using SAMS peptide. 13C6 glucose was added to medium to measure glucose uptake during cellular treatments, which were determined by LC-MS/MS. Cellular glucose was identified by o-toluidine method. Superoxide (O2•–) was identified by EPR-spin-trap, and peroxynitrite (ONOO–) was measured by flow-cytometer using aminophenyl fluorescein dye. Results Short-term incubation of cells with 100 μM ARG in the presence or absence of 30 μM L-NG-Nitroarginine methyl ester (L-NAME) or 30 μM AMPK inhibitor (compound C, CMP-C) increased cellular oxidative stress and overall glucose accumulation with no variation in glucose transporter-1 (GLUT-1), or AMPK activity from control. The increase in total NO2–/NO3– after 2 h 100 μM ARG exposure, was suppressed in cells co-incubated with 30 μM CMP-C or L-NAME. Long-term exposure of ARG with or without CMP-C or L-NAME suppressed NO2–/NO3–, glucose uptake, GLUT-1, AMPK expression and activity below control, and increased overall cellular glucose, O2•– and ONOO–. Gluconeogenesis inhibition with 30 μM 5-Chloro-2-N-2,5-dichlorobenzenesulfonamido-benzoxazole (CDB) during ARG exposure for 2 h maintained overall cellular glucose to control, but increased cellular glucose uptake. Continuous co-incubation with CDB and ARG increased NO2–/NO3–, glucose uptake, GLUT-1, AMPK expression and activity, and maintained overall cellular glucose, O2•– and ONOO– to control conditions. Conclusion The present study provides the fundamental evidence for AMPK as the primary modulator of ARG cellular responses and for regulating the mode of glucose accumulation during short-term and continuous ARG treatments.
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Affiliation(s)
- Srinidi Mohan
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New England, 716 Stevens Avenue, Portland, ME 04103, USA
| | - Harsh Patel
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New England, 716 Stevens Avenue, Portland, ME 04103, USA
| | - Jorge Bolinaga
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New England, 716 Stevens Avenue, Portland, ME 04103, USA
| | - Nathania Soekamto
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New England, 716 Stevens Avenue, Portland, ME 04103, USA
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Luo Q, Cui H, Peng X, Fang J, Zuo Z, Liu J, Wu B, Deng Y. The association between cytokines and intestinal mucosal immunity among broilers fed on diets supplemented with fluorine. Biol Trace Elem Res 2013; 152:212-8. [PMID: 23354543 DOI: 10.1007/s12011-013-9612-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2012] [Accepted: 01/14/2013] [Indexed: 10/27/2022]
Abstract
Fluorine (F) bioaccumulation has been reported in the organs and tissues of organisms, including intestine. The intestinal mucosa is very important to the immune development. Meanwhile, cytokines are present in the normal intestinal mucosal and play an important role in the immune function. Thus, changes of the cytokine contents are related to the state of intestinal mucosal immunity. In this study, we investigated the changes in contents of cytokines such as interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interferon gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) induced by dietary high F in the mucosa of different parts of intestines (duodenum, jejunum, and ileum) by enzyme-linked immunosorbent assay. A total of 280 one-day-old healthy avian broilers were randomly divided into four groups and fed on a corn-soybean basal diet as control diet (F 22.6 mg/kg) or the same basal diet supplemented with 400, 800, and 1,200 mg F/kg (high F groups I, II, and III) in the form of sodium fluoride for 42 days. The experimental data showed that the contents of IL-2, IL-4, IL-6, IFN-γ, and TNF-α in the intestinal mucosa were significantly decreased in the high F groups II and III when compared with those of the control group from 14 to 42 days of age. It was concluded that dietary F in the range of 800-1,200 mg/kg significantly reduced the contents of aforementioned cytokines in the intestinal mucosa of broilers, which could impact the function of intestinal mucosal immunity through the pathways that decreased the lymphocyte population and/or lymphocyte activation.
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Affiliation(s)
- Qin Luo
- Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Yaan, Sichuan 625014, China
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Quirino IEP, Cardoso VN, Santos RDGCD, Evangelista WP, Arantes RME, Fiúza JA, Glória MBA, Alvarez-Leite JI, Batista MA, Correia MITD. The Role of L-Arginine and Inducible Nitric Oxide Synthase in Intestinal Permeability and Bacterial Translocation. JPEN J Parenter Enteral Nutr 2012; 37:392-400. [DOI: 10.1177/0148607112458325] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Iara Eliza Pacífico Quirino
- Departamento de Alimentos da Faculdade de Farmácia da Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Valbert Nascimento Cardoso
- Departamento de Análises Clínicas e Toxicológicas da Faculdade de Farmácia da Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | | | - Warlley Pinheiro Evangelista
- Departamento de Alimentos da Faculdade de Farmácia da Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Rosa Maria Esteves Arantes
- Departamento de Patologia Geral do Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais- Belo Horizonte, Brasil
| | - Jacqueline Araújo Fiúza
- Centro de Pesquisa Renè Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brasil
- Departamento de Parasitologia do Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Maria Beatriz Abreu Glória
- Departamento de Alimentos da Faculdade de Farmácia da Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Jacqueline Isaura Alvarez-Leite
- Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Marina Andrade Batista
- Departamento de Pediatria da Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
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Zhu HL, Liu YL, Xie XL, Huang JJ, Hou YQ. Effect of l-arginine on intestinal mucosal immune barrier function in weaned pigs after Escherichia coli LPS challenge. Innate Immun 2012; 19:242-52. [DOI: 10.1177/1753425912456223] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The effects of l-arginine (Arg) supplementation on intestinal mucosal immune barrier function in weaned pigs after Escherichia coli LPS challenge were evaluated. Twenty-four weaned pigs were allotted to four treatments including: (i) non-challenged control; (ii) LPS-challenged control; (iii) LPS + 0.5% Arg; and (iv) LPS + 1.0% Arg. On d 16, pigs in the LPS, LPS + 0.5% Arg and LPS + 1.0% Arg groups were challenged by injection with 100 µg/kg of body mass LPS, whereas the control group were given sterile saline. At 48 h post-challenge, all pigs were sacrificed for evaluation of small intestinal morphology and mucosal immune barrier function. In the jejunum and ileum, LPS caused villous atrophy and intestinal morphology disruption, whereas 0.5% or 1.0% Arg supplementation mitigated villus atrophy and intestinal morphology impairment caused by LPS challenge. Arg (0.5%) supplementation increased the numbers of IgA-secreting cells, CD8+ and CD4+ T cells in the ileum ( P < 0.05). Arg supplementation prevented the elevation of mast cell numbers induced by LPS challenge ( P < 0.05). Dietary supplementation of Arg caused a decreased lymphocyte apoptosis of Peyer’s patches in pigs challenged by LPS ( P < 0.05). These results indicated that Arg supplementation protects and enhances intestinal mucosal immune barrier function and maintains intestinal integrity in weaned pigs after E. coli LPS challenge.
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Affiliation(s)
- HL Zhu
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, People’s Republic of China
| | - YL Liu
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, People’s Republic of China
| | - XL Xie
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, People’s Republic of China
| | - JJ Huang
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, People’s Republic of China
| | - YQ Hou
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, People’s Republic of China
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Deng Y, Cui H, Peng X, Fang J, Zuo Z, Wang K, Cui W, Wu B. Changes of IgA+ cells and cytokines in the cecal tonsil of broilers fed on diets supplemented with vanadium. Biol Trace Elem Res 2012; 147:149-55. [PMID: 22270623 DOI: 10.1007/s12011-012-9330-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2011] [Accepted: 01/10/2012] [Indexed: 11/25/2022]
Abstract
The cecal tonsil of broiler is known as a secondary lymphoid tissue, which is involved in antigen-specific humoral immune responses. The purpose of this study was to investigate the effects of dietary vanadium on the tissue distribution and quantity of immunoglobulin A-positive (IgA(+)) cell in the cecal tonsil by immunohistochemistry. Simultaneously, the changes in interleukin-6 (IL-6), interleukin-10 (IL-10), interferon gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) contents in the cecal tonsil were also quantified by enzyme-linked immunosorbent assay (ELISA). A total of 420 one-day-old avian broilers were divided into six groups and fed on a corn-soybean basal diet (control diet) or the same diet supplemented respectively with 5, 15, 30, 45, and 60 mg/kg of vanadium in the form of ammonium metavanadate for 42 days. The results showed that the population of the IgA(+) cells in the cecal tonsil were significantly lower (p < 0.05 or p < 0.01) in the 45 and 60 mg/kg groups than that in the control group. Meanwhile, IL-10, IFN-γ and TNF-α contents in the cecal tonsil were significantly decreased (p < 0.05 or p < 0.01) in the 30, 45 and 60 mg/kg groups in comparison with those of the control group. However, IL-6 content in the cecal tonsil was only decreased (p < 0.05 or p < 0.01) in 60 mg/kg at 14 and 28 days of age. In conclusion, dietary vanadium in excess of 30 mg/kg reduced the numbers of the IgA(+) cells and changed the contents of the abovementioned cytokines in the cecal tonsil, which may finally impact the function of local mucosal humoral immunity in broilers.
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Affiliation(s)
- Yuanxin Deng
- Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an, China
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Batista MA, Nicoli JR, dos Santos Martins F, Nogueira Machado JA, Esteves Arantes RM, Pacífico Quirino IE, Davisson Correia MIT, Cardoso VN. Pretreatment With Citrulline Improves Gut Barrier After Intestinal Obstruction in Mice. JPEN J Parenter Enteral Nutr 2011; 36:69-76. [DOI: 10.1177/0148607111414024] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Affiliation(s)
- Marina Andrade Batista
- Post-Graduate Program in Food Science, Pharmacy School, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Jacques Robert Nicoli
- Microbiology Department, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Flaviano dos Santos Martins
- Microbiology Department, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | | | - Rosa Maria Esteves Arantes
- Pathology Department, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Iara Eliza Pacífico Quirino
- Post-Graduate Program in Food Science, Pharmacy School, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | | | - Valbert Nascimento Cardoso
- Department of Clinical and Toxicological Analysis, Pharmacy School, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
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Wang B, Song HY, Yang JR. Progress in the treatment of intestinal barrier dysfunction. Shijie Huaren Xiaohua Zazhi 2011; 19:2251-2256. [DOI: 10.11569/wcjd.v19.i21.2251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Intestinal barrier function plays a pivotal role in the development and progression of some severe diseases such as severe burn, severe acute pancreatitis, tumors, and severe liver disease. With a gradual understanding of the role of intestinal barrier dysfunction in the pathophysiology of various severe diseases, scholars have paid more attention to the basic and clinical research of the treatment of intestinal barrier function. This paper will review the latest advance in the treatment of intestinal barrier dysfunction.
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L-arginine and glycine supplementation in the repair of the irradiated colonic wall of rats. Int J Colorectal Dis 2011; 26:561-8. [PMID: 21350937 DOI: 10.1007/s00384-011-1154-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/01/2011] [Indexed: 02/04/2023]
Abstract
PURPOSE Radiotherapy is widely used for cancer treatment but has harmful effects. This study aimed to assess the effects of L-arginine and glycine supplementation on the colon wall of rats submitted to abdominal irradiation. METHODS Forty male Wistar rats were randomly divided into four groups: I-healthy, II-irradiated with no amino acid supplementation, III-irradiated and supplemented with L-arginine, and IV-irradiated and supplemented with glycine. The animals received supplementation for 14 days, with irradiation being applied on the eighth day of the experiment. All animals underwent laparotomy on the 15th day for resection of a colonic segment for stereologic analysis. Parametric and nonparametric tests were used for statistical analysis, with the level of significance set at p ≤0.05. RESULTS Stereologic analysis showed that irradiation induced a reduction of the total volume of the colon wall of group II and III animals compared to healthy controls, but not of group IV animals supplemented with glycine. The mucosal layer of the irradiated animals of all groups was reduced compared to healthy group I animals, but supplementation with L-arginine and glycine was effective in maintaining the epithelial surface of the mucosal layer. CONCLUSION The present results suggest that glycine supplementation had a superior effect on the irradiated colon wall compared to L-arginine supplementation since it was able to maintain the thickness of the wall and the epithelial surface of the mucosa, whereas L-arginine maintained the partial volume of the epithelium and the epithelial surface, but not the total volume of the intestinal wall.
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Does pharmacological dose of parenteral arginine have beneficial effect in rats with sub-acute peritonitis? Pediatr Surg Int 2010; 26:625-32. [PMID: 20179952 DOI: 10.1007/s00383-010-2582-9] [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] [Accepted: 02/09/2010] [Indexed: 10/19/2022]
Abstract
PURPOSE Peritonitis is a life-threatening condition that may occur as a sequela of intra-abdominal infection. The management of peritonitis includes surgical intervention, antimicrobial therapy, and nutritional support. Arginine has been reported to have beneficial and adverse effects in subjects with inflammation, which might be related to the dose, time, and route of supplementation and the disease severity. So far, the optimal doses of parenteral arginine are not known. In this study, we investigated dose effects of parenterally supplemented arginine on anabolism and arginine-derived metabolites in sub-acute inflammation. METHODS AND MATERIALS Male Wistar rats underwent modified cecal puncture procedure for induction of peritonitis were infused with total parenteral nutrition solutions for 7 days, which contained conventional, low, medium, and high doses of arginine, i.e., 1.61, 2.85, 4.08, and 6.54% of calories from arginine. Healthy, orally fed rats were included as references. RESULTS On day 7, peritonitic rats had significantly decreased body weight, declined serum albumin, and increased serum nitric oxide (NO) and tumor-necrosis factor-alpha compared to references (ANOVA, P < 0.05). There were no dose effects of parenteral arginine on body weight, nitrogen retention, and serum blood urea nitrogen and creatinine in peritonitic rats. In contrast, plasma arginine, proline, and ornithine, and urinary urea nitrogen were significantly increased, whereas serum NO and plasma glutamine were significantly decreased in dose-dependent manners with parenteral arginine. Pharmacological dose of parenteral arginine may increase the synthesis of ornithine, urea, and proline instead of citrulline and NO in peritonitic rats. CONCLUSION These results suggest that high dose of parenteral arginine may facilitate ureagenesis and proline conversion without causing augmentation of NO production in sub-acute inflammation. Therefore, pharmacological dose of parenteral arginine may not have benefits in anabolism but does not cause adverse effect in rats with sub-acute inflammation.
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Effects of dietary arginine on inflammatory mediator and receptor of advanced glycation endproducts (RAGE) expression in rats with streptozotocin-induced type 2 diabetes. Br J Nutr 2010; 104:686-92. [DOI: 10.1017/s000711451000111x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Arginine (Arg) is known to possess numerous useful physiological properties and have immunomodulatory effects.In vitrostudies reported that Arg inhibits advanced glycation endproduct (AGE) formation; however, the effects of Arg on the receptor of AGE (RAGE) expression in inflammatory conditions are not clear. The present study investigated the effects of dietary Arg supplementation on inflammatory mediator production and RAGE expression in type 2 diabetic rats. There were one normal control (NC) group and two diabetic groups in the present study. Rats in the NC group were fed with a regular chow diet. One diabetic group (DM) was fed a common semi-purified diet while the other diabetic group received a diet in which part of the casein was replaced by Arg (DM-Arg) for 8 weeks. Diabetes was induced by an intraperitoneal injection of nicotinamide followed by streptozotocin. Rats with blood glucose levels exceeding 1800 mg/l were considered diabetic. Blood samples and the liver and lungs of the animals were collected at the end of the study for further analysis. Results showed that plasma glucose and fructosamine contents were significantly higher in the diabetic groups than those in the NC group. The DM group had higher fructosamine and C-reactive protein than the DM-Arg group. Immunohistochemical staining showed that the expressions of RAGE in liver and lung tissues were significantly lower in the DM-Arg group than in the DM group. These results suggest that supplemental dietary Arg can decrease AGE–RAGE interactions and consequently reduce tissue damage in rats with type 2 diabetes.
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Supplemental dietary arginine reduces renal RAGE expression and oxidative damage in rats with streptozotocin-induced type 2 diabetes. ACTA ACUST UNITED AC 2010. [DOI: 10.1016/j.eclnm.2010.02.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Effects of early enteral nutrition supplemented with arginine on intestinal mucosal immunity in severely burned mice. Clin Nutr 2009; 29:124-30. [PMID: 19783080 DOI: 10.1016/j.clnu.2009.07.005] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2008] [Revised: 06/16/2009] [Accepted: 07/14/2009] [Indexed: 11/20/2022]
Abstract
BACKGROUND To investigate the effects of early enteral nutrition (EN) supplemented with Arginine (Arg) on intestinal mucosal immunity in severely burned mice. METHODS Forty-four mice were randomly assigned into four groups: a sham injury+EN group (n=10), a sham injury+EN+Arg group (n=10), a burn+EN group (n=12), and a burn+EN+Arg group (n=12) and the mice in two experimental groups received a 20% total body surface area (TBSA), full-thickness scald burn on the back. Then, the burned mice were given a 175 kcal/kg body wt/day of conventional enteral nutrition or an isonitrogenous and isocaloric enteral nutrition supplemented with Arg by gastric gavage for 7 days. There was isonitrogenous and isocaloric intake in two experimental groups. The mice in two control groups received the same procedures as above, except for burn injury. On day 7 after injury, all mice among four groups were euthanized and the entire intestine was harvested. Intestinal immunoglobulin A (IgA) levels, total lymphocyte yield, and lymphocyte subpopulations in Peyer's patches were analyzed. Levels of IFN-gamma, IL-2, IL-4 and IL-10 in gut homogenates were also measured by ELISA. RESULTS Total lymphocyte yield, numbers of lymphocyte subpopulations, and intestinal IgA levels in the EN+ARG group were higher than those in the EN group (p<0.05). Levels of gut tissue cytokines were significantly altered with enteral Arg supplementation: levels of IL-4 and IL-10 were increased, and levels of IFN-gamma and IL-2 declined, when compared with the EN-fed mice (p<0.05). CONCLUSIONS The results of this study suggested that enteral nutrition supplemented with Arg has changed the cytokine concentrations in intestinal homogenates from a pro- to an anti-inflammatory profile, increased sIgA levels and changed lymphocytes in severely burned mice.
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Yeh CL, Pai MH, Li CC, Tsai YL, Yeh SL. Effect of arginine on angiogenesis induced by human colon cancer: in vitro and in vivo studies. J Nutr Biochem 2009; 21:538-43. [PMID: 19447018 DOI: 10.1016/j.jnutbio.2009.03.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2008] [Revised: 01/13/2009] [Accepted: 03/04/2009] [Indexed: 10/20/2022]
Abstract
This study investigated the effect of arginine (Arg) supplementation on angiogenesis in human colon cancer. The in vitro study investigated the effects of different Arg levels and inducible nitric oxide (iNO) synthase inhibitor on angiogenic protein expressions stimulated by SW480 cells. The results showed that the production of vascular endothelial growth factor (VEGF), basic fibroblast growth factor with 100 and 1000 micromol/L Arg and matrix metalloproteinase (MMP)-2 with 1000 micromol/L Arg was lower than that with 0 and 50 micromol/L Arg. Inhibition of iNO resulted in higher angiogenic protein expressions comparable with groups with low Arg administration, indicating that Arg administration at levels similar to or higher than physiological concentrations reduced the progression of colon cancer, and iNO may partly play a role in reducing angiogenesis. The in vivo study used a human colon cancer xenograft model in nude mice. Mice were inoculated with 1x10(7) SW480 cells and assigned to two groups. The control group was fed a semipurified diet, while the experimental group was supplied an Arg-supplemented diet. After 5 weeks, tumors were harvested and spleens were excised for further analysis. Results showed that the MMP-2, MMP-9 and VEGF receptor levels in tumors were significantly lower, whereas tumor NO levels and spleen natural killer (NK) cell activities were higher in the Arg group than in the control group. These results were consistent with the in vitro study that dietary Arg supplementation inhibits the progression of colon cancer possibly by increasing NO secretion and consequently enhancing NK cell activity.
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Affiliation(s)
- Chiu-Li Yeh
- Institute of Nutrition and Health Sciences, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan
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Biondo PD, Goruk S, Ruth MR, O'Connell E, Field CJ. Effect of CVT-E002 (COLD-fX) versus a ginsenoside extract on systemic and gut-associated immune function. Int Immunopharmacol 2008; 8:1134-42. [PMID: 18550018 DOI: 10.1016/j.intimp.2008.04.003] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2008] [Revised: 03/27/2008] [Accepted: 04/10/2008] [Indexed: 11/18/2022]
Abstract
CVT-E002 (sold commercially as COLD-fX) is a patented, polysaccharide-rich extract of North American ginseng (Panax quinquefolium) with purported beneficial effects on influenza and the common cold, although its mechanism of action is largely unknown. This study was conducted to determine the effects of feeding CVT-E002 versus a ginsenoside-containing extract on systemic and gut-associated immune function. For 7 days, male weanling Sprague-Dawley rats (n=10/group) were fed one of four diets: control, low CVT-E002 (450 mg/kg), high CVT-E002 (900 mg/kg), or ginsenoside (450 mg/kg). Lymphocytes were isolated from spleen, mesenteric lymph nodes and Peyer's patches, and immune cell proportions and cytokine production were measured. IgA-positive cells in the jejunum were also assayed. CVT-E002 consumption (particularly at the higher dose) decreased spleen IL-2 and IFN-gamma production following ConA and/or LPS stimulation for 24 or 48 h (P<0.05). Also, CVT-E002-fed rats had a lower proportion of total CD3+ cells and activated T cells (P<0.05). After 48 h of ConA stimulation, spleen IL-1beta production was higher (P<0.05) for animals fed the high dose CVT-E002, whereas TNF-alpha production did not differ significantly from the control group. Feeding the ginsenoside diet resulted in lower (P<0.05) spleen IL-2 production, but the IFN-gamma, TNF-alpha and IL-1beta response to ConA was not different from control animals at 48 h. A higher proportion of jejunal IgA-positive cells was found in rats fed the ginsenoside diet (P<0.05). In conclusion, feeding CVT-E002 modifies systemic immune responses and appears to affect gut-associated immunity in a manner distinct from that of ginsenoside-containing extracts of North American ginseng.
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Affiliation(s)
- Patricia D Biondo
- Alberta Institute for Human Nutrition, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2P5
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Yeh CL, Lee CH, Chen SC, Hou YC, Yeh SL. Effects of arginine-containing total parenteral nutrition on N balance and phagocytic activity in rats undergoing a partial gastrectomy. Br J Nutr 2007; 93:267-72. [PMID: 15788120 DOI: 10.1079/bjn20041326] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The present study investigated the effect of arginine (Arg)-containing parenteral nutrition on phagocytic activity to elucidate the possible roles of Arg in the secretion of anabolic hormones and N balance in rats undergoing gastrectomy. Rats were divided into two experimental groups and received total parenteral nutrition (TPN). The TPN solutions were isonitrogenous and identical in nutrient compositions except for differences in amino acid content. One group received conventional TPN, the other group replaced 2 % of the total energy as Arg. After receiving TPN for 3 d, one-third of the rats in each experimental group were killed as the baseline group. The remaining rats underwent a partial gastrectomy and were killed 1 or 3 d after surgery. The results showed that there were no differences in N balance, plasma growth hormone and insulin-like growth factor-1 levels between the two groups before or after surgery. The phagocytic activity of peritoneal macrophages was higher in the Arg group than in the control group 1 d after surgery. There were no differences in the phagocytic activities of blood polymorphonuclear neutrophils between the two groups at various time points. TNF-α levels in peritoneal lavage fluid were lower in the Arg group than in the control group on post-operative day 3. These results suggest that parenterally infused Arg enhances phagocytic activity and reduces the production of inflammatory mediators at the site of injury. However, Arg supplementation did not influence the secretion of anabolic hormones nor N balance in rats with a partial gastrectomy.
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Affiliation(s)
- Chiu-Li Yeh
- Institute of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan
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A review on the interactions between gut microflora and digestive mucosal immunity. Possible ways to improve the health of rabbits. Livest Sci 2007. [DOI: 10.1016/j.livsci.2006.09.005] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Quirino IEP, Correia MITD, Cardoso VN. The impact of arginine on bacterial translocation in an intestinal obstruction model in rats. Clin Nutr 2007; 26:335-40. [PMID: 17307280 DOI: 10.1016/j.clnu.2006.12.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2006] [Revised: 12/11/2006] [Accepted: 12/19/2006] [Indexed: 11/28/2022]
Abstract
BACKGROUND & AIMS Arginine has been shown to have multiple beneficial metabolic and immunologic effects in stress situations. Supplementation of arginine has been shown to promote wound healing and intestinal mucosal recovery after trauma, ischemia or intestinal resection. Bacterial translocation has also been evaluated although with conflicting results and using different assessing techniques. Therefore, the aim of this study was to evaluate the effects of arginine on bacterial translocation in an intestinal obstruction model in rats using Escherichia coli labeled with 99mTechnetium. METHODS Male Wistar rats (250-350 g) were randomized to receive conventional chow, diet supplemented with pure arginine or diet supplemented with an immunonutrition enteral formula, enriched with arginine, omega-3 fatty acid and RNA. After 7 days, the animals were anesthetized. Terminal ileum was isolated and a ligature was placed around it. E. coli labeled with 99mTechnetium (99mTc-E. coli) was inoculated into the intestinal lumen (terminal ileum). After 24 h, the animals were sacrificed. Blood, mesenteric lymph nodes (MLN), liver, spleen and lungs were removed for radioactivity determination. RESULTS Arginine supplementation (300 mg/day, 600 mg/day or present in the enteral formula) reduced the level of bacterial translocation when compared with the control group (p<0.05). This was shown by significantly decrease uptake of 99mTc-E. coli in blood, MLN, liver, spleen and lungs of the animals in the experimental groups (p < 0.05). CONCLUSIONS These results have shown that arginine was able to decrease bacteria translocation despite intestinal obstruction. There are several mechanisms which might explain the role of arginine and these will be the subject of future studies.
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Shang HF, Hsu CS, Yeh CL, Pai MH, Yeh SL. Effects of arginine supplementation on splenocyte cytokine mRNA expression in rats with gut-derived sepsis. World J Gastroenterol 2006; 11:7091-6. [PMID: 16437653 PMCID: PMC4725087 DOI: 10.3748/wjg.v11.i45.7091] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the effects of arginine (Arg)-enriched diets before sepsis and/or Arg-containing total parenteral nutrition (TPN) after sepsis or both on cytokine mRNA expression levels in splenocytes of rats with gut-derived sepsis. METHODS Rats were assigned to four experimental groups. Groups 1 and 2 were fed with a semipurified diet, while groups 3 and 4 had part of the casein replaced by Arg which provided 2% of the total calories. After the rats were fed with these diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP), at the same time an internal jugular vein was cannulated. All rats were maintained on TPN for 3 d. Groups 1 and 3 were infused with conventional TPN, while groups 2 and 4 were supplemented with Arg which provided 2% of the total calories in the TPN solution. All rats were killed 3 d after CLP to examine their splenocyte subpopulation distribution and cytokine expression levels. RESULTS Plasma interleukin (IL)-2, IL-4, tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN-gamma) were not detectable 3 d after CLP. There were no differences in the distributions of CD45Ra(+), CD3(+), CD4(+), and CD8(+) cells in whole blood and splenocytes among the four groups. The splenocyte IL-2 mRNA expression in the Arg-supplemented groups was significantly higher than that in group 1. IL-4 mRNA expression in groups 3 and 4 was significantly higher than that in groups 1 and 2. The mRNA expression of IL-10 and IFN-gamma was significantly higher in group 4 than in the other three groups. There was no difference in TNF-alpha mRNA expression among the four groups. CONCLUSION The influence of Arg on the whole blood and splenic lymphocyte subpopulation distribution is not obvious. However, Arg administration, especially before and after CLP, significantly enhances the mRNA expression levels of Th1 and Th2 cytokines in the spleen of rats with gut-derived sepsis.
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Affiliation(s)
- Huey-Fang Shang
- School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan, China
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