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El Gazzar WB, Sliem RE, Bayoumi H, Nasr HE, Shabanah M, Elalfy A, Radwaan SE, Gebba MA, Mansour HM, Badr AM, Amer MF, Ashour SS, Morsi H, Aboelkomsan ESAF, Baioumy B, Sayed AEDH, Farag AA. Melatonin Alleviates Intestinal Barrier Damaging Effects Induced by Polyethylene Microplastics in Albino Rats. Int J Mol Sci 2023; 24:13619. [PMID: 37686424 PMCID: PMC10488227 DOI: 10.3390/ijms241713619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 08/27/2023] [Accepted: 08/29/2023] [Indexed: 09/10/2023] Open
Abstract
There have been concerns about the potential health risks posed by microplastics (MP). The detection of MP in a variety of food products revealed that humans are ingesting MP. Nevertheless, there is a paucity of data about their impacts, as well as their uptake, on intestinal barrier integrity. This study examined the toxic effects of oral administration of two doses of polyethylene microplastics (PE-MP) (3.75 or 15 mg/kg/day for 5 weeks; mean particle size: 4.0-6.0 µm) on the intestinal barrier integrity in rats. Moreover, the effect of melatonin treatment with MP exposure was also assessed. The PE-MP particle uptake, histopathological changes, Alcian blue staining, Muc2 mRNA, proinflammatory cytokines (IL-1β and TNF-α), and cleaved caspase-3, as well as tight junction proteins (claudin-1, myosin light-chain kinase (MLCK), occludin, and zonula occludens-1 (ZO-1)) were assessed. Oral administration of PE-MP resulted in apparent jejunal histopathological alterations; significantly decreased mucin secretion, occludin, ZO-1, and claudin-1 expression; and significantly upregulated MLCK mRNA, IL-1β concentration, and cleaved caspase-3 expression. Melatonin reversed these altered parameters and improved the PE-MP-induced histopathological and ultrastructure changes. This study highlighted the PE-MP's toxic effect on intestinal barrier integrity and revealed the protective effect of melatonin.
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Affiliation(s)
- Walaa Bayoumie El Gazzar
- Department of Anatomy, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Benha University, Benha 13518, Egypt;
| | - Rania E. Sliem
- Department of Zoology, Faculty of Science, Benha University, Benha 13518, Egypt; (R.E.S.); (S.E.R.)
| | - Heba Bayoumi
- Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha 13518, Egypt; (H.B.); (A.E.)
| | - Hend Elsayed Nasr
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Benha University, Benha 13518, Egypt;
| | - Manar Shabanah
- Department of Physiology, Faculty of Medicine, Mansoura University, Mansoura 35511, Egypt;
| | - Amira Elalfy
- Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha 13518, Egypt; (H.B.); (A.E.)
| | - Shaimaa E. Radwaan
- Department of Zoology, Faculty of Science, Benha University, Benha 13518, Egypt; (R.E.S.); (S.E.R.)
| | - Mohammed A. Gebba
- Department of Anatomy and Embryology, Faculty of Medicine, Benha University, Benha 13518, Egypt; (M.A.G.)
- Department of Anatomy and Embryology, Faculty of Medicine, Merit University, Sohag 82524, Egypt
| | - Heba M. Mansour
- Department of Pharmacology and Toxicology, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City 12573, Egypt;
| | - Amul M. Badr
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo 11451, Egypt; (A.M.B.); (M.F.A.); (S.S.A.); (H.M.)
| | - Marwa Fathy Amer
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo 11451, Egypt; (A.M.B.); (M.F.A.); (S.S.A.); (H.M.)
| | - Sara S. Ashour
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo 11451, Egypt; (A.M.B.); (M.F.A.); (S.S.A.); (H.M.)
| | - Heba Morsi
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo 11451, Egypt; (A.M.B.); (M.F.A.); (S.S.A.); (H.M.)
| | | | - Bodour Baioumy
- Department of Anatomy and Embryology, Faculty of Medicine, Benha University, Benha 13518, Egypt; (M.A.G.)
| | | | - Amina A. Farag
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha 13518, Egypt;
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Oubaid EN, Abu-Raghif A, Al-Sudani IM. Ibudilast ameliorates experimentally induced colitis in rats via down-regulation of proinflammatory cytokines and myeloperoxidase enzyme activity. PHARMACIA 2023. [DOI: 10.3897/pharmacia.70.e98715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2023] Open
Abstract
Objectives: This study was carried out to explore the possible anti-inflammatory effect of ibudilast on acetic acid-induced colitis in rats.
Methods: Fifty adult Wistar rats were separated into 5 groups, including the control group, acetic acid group, acetic acid + vehicle, acetic acid + sulfasalazine (100 mg/kg/day)group, and acetic acid + ibudilast (30 mg/kg/day) group. Colitis was induced in rats by the inter-rectal installation of 2 ml of 4% (v/v) acetic acid. Sulfasalazine and ibudilast were administered orally for ten days after 2 hours of induction.
Results: The treatment with ibudilast significantly reduced disease activity index (DAI), macroscopic colonic scores (MAC), and histopathological changes induced by acetic acid. Also, ibudilast markedly decreased the expression of proinflammatory markers (TNF-α and IL-1β) in colonic tissue. Moreover, ibudilast inhibited myeloperoxidase (MPO) enzyme activity that was increased by acetic acid.
Conclusion: Therefore, ibudilast may have a therapeutic effect in the management of ulcerative colitis.
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Miao Z, Miao Z, Teng X, Xu S. Melatonin alleviates lead-induced fatty liver in the common carps (Cyprinus carpio) via gut-liver axis. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2023; 317:120730. [PMID: 36427828 DOI: 10.1016/j.envpol.2022.120730] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/11/2022] [Accepted: 11/21/2022] [Indexed: 06/16/2023]
Abstract
As a widespread aquatic environmental contaminant, Lead (Pb) can provoke hepatic injury in various animals. Melatonin (MT) plays a crucial role in the regulation of inflammatory response. Accumulating evidence elucidates exogenous toxins can elicit hepatic lipid metabolic disorders by influencing the gut microbiome. Nevertheless, the effects of Pb on gut microbiota and hepatic lipid metabolism of the common carps, and whether MT can prevent and cure Pb-induced toxicity via regulating microbiome remains unknown. Here, metagenomic and transcriptomic analysis were subsequently implemented to identify the Pb exposure-triggered prominent alternation of gut-liver signal. In the present study the severe intestinal injury and fatty liver formation caused by Pb in common carp were preliminarily determined. Metagenomic analysis confirmed that the gut microbiome dominant phyla, family and genus of the common carps were Fusobacteria, Fusobacteriaceae and Cetobacterium. Meanwhile, lipopolysaccharide (LPS) biosynthesis pathway was regarded as one of the main responsible for Pb exposure. Subsequently, LPS was demonstrated as the Pb-triggered microbial-derived signal of the common carps by ELISA analysis, and involves in the hepatic metabolic disorders via deteriorating the intestinal barrier. Additionally, it confirmed that hepatocytes ferroptosis associated with Pb-evoked fatty liver of the common carps, and the aggravation of lysosomal dyshomeostasis as well as inhibition of AMPK phosphorylation were referred to lipid metabolic disorders. The results of the present study demonstrated microbial-derived signal induced by aquatic Pb contaminant cause fatty liver formation in the common carps, and the protective effects of MT on Pb toxicity were performed by receding LPS over-synthesis, restraining microbiota-sourced LPS transport, along with attenuation of hepatocytes ferroptosis.
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Affiliation(s)
- Zhiying Miao
- College of Life Science, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Zhiruo Miao
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Xiaohua Teng
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Shiwen Xu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
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Vaghari-Tabari M, Moein S, Alipourian A, Qujeq D, Malakoti F, Alemi F, Yousefi B, Khazaie S. Melatonin and inflammatory bowel disease: From basic mechanisms to clinical application. Biochimie 2022; 209:20-36. [PMID: 36535545 DOI: 10.1016/j.biochi.2022.12.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 10/25/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022]
Abstract
Inflammatory bowel disease is a chronic inflammatory disease and has periods of recurrence and remission. Improper immune responses to gut flora bacteria, along with genetic susceptibility, appear to be involved in causing this complex disease. It seems dysbiosis and oxidative stress may also be involved in IBD pathogenesis. A significant number of clinical studies have shown an interesting association between sleep disturbances and IBD. Studies in animal models have also shown that sleep deprivation has a significant effect on the pathogenesis of IBD and can aggravate inflammation. These interesting findings have drawn attention to melatonin, a sleep-related hormone. Melatonin is mainly produced by the pineal gland, but many tissues in the body, including the intestines, can produce it. Melatonin can have an interesting effect on the pathogenesis of IBD. Melatonin can enhance the intestinal mucosal barrier, alter the composition of intestinal bacteria in favor of bacteria with anti-inflammatory properties, regulate the immune response, alleviate inflammation and attenuate oxidative stress. It seems that, melatonin supplementation is effective in relieving inflammation and healing intestinal ulcers in IBD animal models. Some clinical studies have also shown that melatonin supplementation as an adjuvant therapy may be helpful in reducing disease activity in IBD patients. In this review article, in addition to reviewing the effects of sleep disturbances and melatonin on key mechanisms involved in the pathogenesis of IBD, we will review the findings of clinical studies regarding the effects of melatonin supplementation on IBD treatment.
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Affiliation(s)
- Mostafa Vaghari-Tabari
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Soheila Moein
- Medicinal Plants Processing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Alipourian
- Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Durdi Qujeq
- Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran
| | - Faezeh Malakoti
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Forough Alemi
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Bahman Yousefi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Sepideh Khazaie
- Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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Liu GH, Zhuo XC, Huang YH, Liu HM, Wu RC, Kuo CJ, Chen NH, Chuang LP, Lin SW, Chen YL, Yang HY, Lee TY. Alterations in Gut Microbiota and Upregulations of VPAC2 and Intestinal Tight Junctions Correlate with Anti-Inflammatory Effects of Electroacupuncture in Colitis Mice with Sleep Fragmentation. BIOLOGY 2022; 11:962. [PMID: 36101343 PMCID: PMC9311573 DOI: 10.3390/biology11070962] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 06/14/2022] [Accepted: 06/21/2022] [Indexed: 11/16/2022]
Abstract
The relationship between inflammatory bowel disease and sleep disturbances is complicated and of increasing interest. We investigated the inflammatory and immunological consequences of EA in sleep-deprived colitis and found that dextran sulfate sodium (DSS)-induced colitis in sleep-fragmented (SF) mice was more severe than that in mice with normal sleep. This increase in the severity of colitis was accompanied by reduced body weight, shortened colon length, and deteriorated disease activity index. DSS with SF mice presented obvious diminished intestinal tight junction proteins (claudin-1 and occludin), elevated proinflammatory cytokines (CRP, IFN-γ, IL-6), lowered melatonin and adiponectin levels, downregulated vasoactive intestinal peptide (VIP) type 1 and 2 receptor (VPAC1, VPAC2) expression, and decreased diversity of gut bacteria. EA ameliorated colitis severity and preserved the performance of the epithelial tight junction proteins and VIP receptors, especially VPAC2. Meanwhile, the innate lymphoid cells-derived cytokines in both group 2 (IL-4, IL5, IL-9, IL-13) and group 3 (IL-22, GM-CSF) were elevated in mice colon tissue. Furthermore, dysbiosis was confirmed in the DSS group with and without SF, and EA could maintain the species diversity. Firmicutes could be restored, such as Lachnospiraceae, and Proteobacteria become rebalanced, mainly Enterobacteriaceae, after EA intervention. On the other hand, SF plays different roles in physiological and pathological conditions. In normal mice, interrupted sleep did not affect the expression of claudin-1 and occludin. But VPAC1, VPAC2, and gut microbiota diversity, including Burkholderiaceae and Rhodococcus, were opposite to mice in an inflamed state.
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Affiliation(s)
- Geng-Hao Liu
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (G.-H.L.); (R.-C.W.); (N.-H.C.)
- Graduate Institute of Traditional Chinese Medicine, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan;
- Division of Acupuncture and Moxibustion, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan;
- Sleep Center, Chang Gung Memorial Hospital, Taoyuan 333008, Taiwan; (L.-P.C.); (S.-W.L.)
| | - Xin-Cheng Zhuo
- Department of General Medicine, Taipei Medical University Hospital, Taipei 110301, Taiwan;
| | - Yueh-Hsiang Huang
- Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taipei 105406, Taiwan;
| | - Hsuan-Miao Liu
- Graduate Institute of Traditional Chinese Medicine, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan;
| | - Ren-Chin Wu
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (G.-H.L.); (R.-C.W.); (N.-H.C.)
- Department of Anatomic Pathology, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
| | - Chia-Jung Kuo
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan;
| | - Ning-Hung Chen
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (G.-H.L.); (R.-C.W.); (N.-H.C.)
- Sleep Center, Chang Gung Memorial Hospital, Taoyuan 333008, Taiwan; (L.-P.C.); (S.-W.L.)
- Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
| | - Li-Pang Chuang
- Sleep Center, Chang Gung Memorial Hospital, Taoyuan 333008, Taiwan; (L.-P.C.); (S.-W.L.)
- Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
| | - Shih-Wei Lin
- Sleep Center, Chang Gung Memorial Hospital, Taoyuan 333008, Taiwan; (L.-P.C.); (S.-W.L.)
- Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
| | - Yen-Lung Chen
- Division of Acupuncture and Moxibustion, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan;
- Sleep Center, Chang Gung Memorial Hospital, Taoyuan 333008, Taiwan; (L.-P.C.); (S.-W.L.)
| | - Huang-Yu Yang
- Department of Nephrology, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
- Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Tzung-Yan Lee
- Graduate Institute of Traditional Chinese Medicine, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan;
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung 204201, Taiwan
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Ye H, Huang S, Song Y, Liu H, Zhao X, Zhao D, Mi F, Wang X, Zhang X, Du J, Zhu N, Zhang L, Zhao Y. Gene co-expression analysis identifies modules related to insufficient sleep in humans. Sleep Med 2021; 86:68-74. [PMID: 34464880 DOI: 10.1016/j.sleep.2021.08.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 07/12/2021] [Accepted: 08/05/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Insufficient sleep and circadian rhythm disruption may cause cancer, obesity, cardiovascular disease, and cognitive impairment. The underlying mechanisms need to be elucidated. METHOD Weighted gene co-expression network analysis (WGCNA) was used to identify co-expressed modules. Connectivity Map tool was used to identify candidate drugs based on top connected genes. R ptestg package was utilized to detected module rhythmicity alteration. A hypergeometric test was used to test the enrichment of insomnia SNP signals in modules. Google Scholar was used to validate the modules and hub genes by literature. RESULTS We identified a total of 45 co-expressed modules. These modules were stable and preserved. Eight modules were correlated with sleep restriction duration. Module rhythmicity was disrupted in sleep restriction subjects. Hub genes that involve in insufficient sleep also play important roles in sleep disorders. Insomnia GWAS signals were enriched in six modules. Finally, eight drugs associated with sleep disorders were identified. CONCLUSION Systems biology method was used to identify sleep-related modules, hub genes, and candidate drugs. Module rhythmicity was altered in sleep insufficient subjects. Thiamphenicol, lisuride, timolol, and piretanide are novel candidates for sleep disorders.
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Affiliation(s)
- Hua Ye
- Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Shiliang Huang
- Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Yufei Song
- Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Huiwei Liu
- Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Xiaosu Zhao
- Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Dan Zhao
- Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Fangxia Mi
- Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Xinxue Wang
- Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Xuesong Zhang
- Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Jinman Du
- Physical Examination Center, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Na Zhu
- Physical Examination Center, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Liangshun Zhang
- Physical Examination Center, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Yibin Zhao
- Department of Anus & Intestine Surgery, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China.
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Proteomic Analysis Revealed the Characteristics of Key Proteins Involved in the Regulation of Inflammatory Response, Leukocyte Transendothelial Migration, Phagocytosis, and Immune Process during Early Lung Blast Injury. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:8899274. [PMID: 34007409 PMCID: PMC8099533 DOI: 10.1155/2021/8899274] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 03/29/2021] [Accepted: 04/08/2021] [Indexed: 12/17/2022]
Abstract
Previous studies found that blast injury caused a significant increased expression of interleukin-1, IL-6, and tumor necrosis factor, a significant decrease in the expression of IL-10, an increase in Evans blue leakage, and a significant increase in inflammatory cell infiltration in the lungs. However, the molecular characteristics of lung injury at different time points after blast exposure have not yet been reported. Therefore, in this study, tandem mass spectrometry (TMT) quantitative proteomics and bioinformatics analysis were used for the first time to gain a deeper understanding of the molecular mechanism of lung blast injury at different time points. Forty-eight male C57BL/6 mice were randomly divided into six groups: control, 12 h, 24 h, 48 h, 72 h, and 1 w after low-intensity blast exposure. TMT quantitative proteomics and bioinformatics analysis were performed to analyze protein expression profiling in the lungs from control and blast-exposed mice, and differential protein expression was verified by Western blotting. The results demonstrated that blast exposure induced severe lung injury, leukocyte infiltration, and the production of inflammatory factors in mice. After analyzing the expression changes in global proteins and inflammation-related proteomes after blast exposure, the results showed that a total of 6861 global proteins and 608 differentially expressed proteins were identified, of which 215, 128, 187, 232, and 65 proteins were identified at 12 h, 24 h, 48 h, 72 h, and 1 week after blast exposure, respectively. Moreover, blast exposure-induced 177 differentially expressed proteins were associated with inflammatory responses, which were enriched in the inflammatory response regulation, leukocyte transendothelial migration, phagocytosis, and immune response. Therefore, blast exposure may induce early inflammatory response of lung tissue by regulating the expression of key proteins in the inflammatory process, suggesting that early inflammatory response may be the initiating factor of lung blast injury. These data can provide potential therapeutic candidates or approaches for the development of future treatment of lung blast injury.
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Yousefi-Manesh H, Dejban P, Mumtaz F, Abdollahi A, Chamanara M, Dehpour A, Hasanvand A, Rashidian A. Risperidone attenuates acetic acid-induced colitis in rats through inhibition of TLR4/NF-kB signaling pathway. Immunopharmacol Immunotoxicol 2020; 42:464-472. [PMID: 32787472 DOI: 10.1080/08923973.2020.1808987] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
AIM The purpose of the present study is to explore the anti-inflammatory potential of risperidone in acetic acid-induced rat colitis through inhibition of TLR4/NF-kB pathway. METHODS Acute colitis induction was done by intra-rectal administration of 2 mL of 4% diluted acetic acid solution. Two h after colitis induction, dexamethasone (2 mg/kg) as standard drugorrisperidone (2, 4 and 6 mg/kg) were administered orally to wistar rats for five consecutive days. 24 h after the last treatment, animals were sacrificed by cervical dislocation. Macroscopic and microscopic damage evaluation was done. Biochemical and ELISA methods were used to assess myeloid peroxidase (MPO) enzyme activity and tumor necrosis factor-α (TNF-α) level respectively. Moreover, immunohistochemistry (IHC) was performed to detect the expression of TLR4 and pNF-kBproteins. RESULTS Dexamethasone (2 mg/kg) or risperidone (2, 4 and 6 mg/kg) improved acetic acid-induced macroscopic (p < .001) and microscopic lesions. Additionally, risperidone (2, 4 and 6 mg/kg) inhibited the activity of MPO and TNF-α (p < .01, p < .001) in the colon tissue compared to acetic acid group. Furthermore, bothdexamethasone and risperidone (2, 4 and 6 mg/kg) significantly reduced acetic acid-induced expression of TLR4and pNF-kB proteins (p < .05, p < .01, p < .001). CONCLUSION The anti-inflammatory effect of risperidone on acetic acid-induced colitis in rats may involve inhibition of TLR4 and NF-kB signaling pathway.
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Affiliation(s)
- Hasan Yousefi-Manesh
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Pegah Dejban
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Faiza Mumtaz
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Abdollahi
- Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Chamanara
- Department of Pharmacology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Ahmadreza Dehpour
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Amin Hasanvand
- Department of Pharmacology, School of Medicine, Lorestan University of Medical Sciences, Lorestan, Iran
| | - Amir Rashidian
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
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Park YS, Kim SH, Park JW, Kho Y, Seok PR, Shin JH, Choi YJ, Jun JH, Jung HC, Kim EK. Melatonin in the colon modulates intestinal microbiota in response to stress and sleep deprivation. Intest Res 2020; 18:325-336. [PMID: 32564539 PMCID: PMC7385569 DOI: 10.5217/ir.2019.00093] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 02/26/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND/AIMS Stress is closely related to the deterioration of digestive disease. Melatonin has potent anti-inflammatory properties. The objective of this study was to determine the effect of water stress (WS) and sleep deprivation (SD) on intestinal microbiota and roles of melatonin in stressful condition. METHODS We used C57BL/6 mice and specially designed water bath for stress and SD for 10 days. We measured melatonin concentrations in serum, feces, and colon tissues by high-performance liquid chromatography. Genomic DNA was extracted from feces and amplified using primers targeting V3 to V4 regions of bacterial 16S ribosomal RNA genes. RESULTS Compared to the control, melatonin concentration was lower in the WS and SD. Fecal concentration was 0.132 pg/mL in control, 0.062 pg/mL in WS, and 0.068 pg/mL in SD. In colon tissue, it was 0.45 pg/mL in control, 0.007 pg/mL in WS, and 0.03 pg/mL in SD. After melatonin treatment, melatonin concentrations in feces and colon tissue were recovered to the level of control. Metagenomic analysis of microbiota showed abundance in colitogenic microbiota in WS and SD. Melatonin injection attenuated this harmful effect. WS and SD showed decreased Lactobacillales and increased Erysipelotrichales and Enterobacteriales. Melatonin treatment increased Akkermansia muciniphila and Lactobacillus and decreased Bacteroides massiliensis and Erysipelotrichaceae. CONCLUSIONS This study showed that stress and SD could affect intestinal dysbiosis and increase colitogenic microbiota, which could contribute to the aggravating digestive disease. Melatonin concentrations in feces and colon tissue decreased under WS and SD. Melatonin treatment brought recovery of melatonin concentration in colon tissue and modulating dysbiosis of intestinal microbiota.
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Affiliation(s)
- Young Sook Park
- Division of Gastroenterology, Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, Korea
| | - Soo Hyung Kim
- Division of Gastroenterology, Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, Korea
| | - Jong Won Park
- Division of Gastroenterology, Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, Korea
| | - Younglim Kho
- Department of Health, Environment and Safety, Graduate School of Health Science, Eulji University, Seongnam, Korea
| | - Pu Rum Seok
- Departemnt of Biomedical Laboratory Science, Graduate School of Health Science, Eulji University, Seongnam, Korea
| | - Jae-Ho Shin
- Department of Biomedical Laboratory Science, Eulji University, Seongnam, Korea
| | - Yoon Ji Choi
- Departemnt of Biomedical Laboratory Science, Graduate School of Health Science, Eulji University, Seongnam, Korea
| | - Jin-Hyun Jun
- Departemnt of Biomedical Laboratory Science, Graduate School of Health Science, Eulji University, Seongnam, Korea
| | - Hee Chan Jung
- Division of Gastroenterology, Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, Korea
| | - Eun Kyung Kim
- Department of Pathology, Eulji University School of Medicine, Seoul, Korea
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10
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Goudarzi R, Partoazar A, Mumtaz F, Yousefi-Manesh H, Abdollahi A, Dehpour A, Rashidian A. Arthrocen, an avocado-soy unsaponifiable agent, improves acetic acid-induced colitis in rat by inhibition of NF-kB signaling pathway. J Food Biochem 2020; 44:e13244. [PMID: 32441355 DOI: 10.1111/jfbc.13244] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Revised: 03/29/2020] [Accepted: 03/29/2020] [Indexed: 12/14/2022]
Abstract
The goal of the current study was to evaluate the anti-inflammatory effect of Arthrocen against acetic acid-induced colitis in rats. Acute inflammation was produced through intrarectal administration of 2 ml diluted acetic acid (4%) solution. All interventions were carried out for 5 days after colitis induction. Arthrocen was administered orally at doses of 30, 60, and 120 mg kg-1 day-1 . Then, macroscopic and microscopic studies were performed. Myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α) activity were measured by biochemical and ELISA methods, respectively. Immunohistochemistry was done to investigate the expression of pNF-κB. The results of this study demonstrated that Arthrocen reduced macroscopic and microscopic damage compared to the acetic acid group. Furthermore, Arthrocen decreased the activity of MPO and TNF-α as well as the protein expression of pNF-kB in rat colon tissue. The results of the current study revealed the anti-inflammatory activity of Arthrocen in acetic acid mediated colon inflammation through suppressing the NF-κB pathway. PRACTICAL APPLICATIONS: Inflammatory bowel disease (IBD) is an immune-mediated chronic relapsing disorder affecting the gastrointestinal tract (GIT) characterized by chronic bowel inflammation. A plant-based dietary supplement containing avocado and soy unsaponifiable extracts in a ratio of 1:2 is known as Arthrocen. Arthrocen can be used as a complementary drug beside current drugs in clinical trials for the treatment of IBD.
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Affiliation(s)
- Ramin Goudarzi
- Division of Research and Development, Pharmin USA, LLC, San Jose, CA, USA
| | - Alireza Partoazar
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Faiza Mumtaz
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hasan Yousefi-Manesh
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Abdollahi
- Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmadreza Dehpour
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Rashidian
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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11
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Collins SM. Interrogating the Gut-Brain Axis in the Context of Inflammatory Bowel Disease: A Translational Approach. Inflamm Bowel Dis 2020; 26:493-501. [PMID: 31970390 PMCID: PMC7054772 DOI: 10.1093/ibd/izaa004] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Indexed: 12/14/2022]
Abstract
This review examines preclinical and clinical studies relevant to our understanding of how the bidirectional gut-brain axis influences the natural history of inflammatory bowel disease. Preclinical studies provide proof of concept that preexisting behavioral illness, such as depression, results in increased susceptibility to inflammatory stimuli and that commonly used classes of antidepressants protect against this vulnerability. However, clinical studies suggesting behavioral illness as a risk factor for IBD and a protective role for antidepressants have relied primarily on symptom-reporting rather than objective measurements of inflammation. In terms of gut-to-brain signaling, there is emerging evidence from preclinical and clinical observation that intestinal inflammation alters brain functions, including the induction of mood disorders, alteration of circadian rhythm both centrally and peripherally, and changes in appetitive behaviors. Furthermore, preclinical studies suggest that effective treatment of intestinal inflammation improves associated behavioral impairment. Taken together, the findings of this review encourage a holistic approach to the management of patients with IBD, accommodating lifestyle issues that include the avoidance of sleep deprivation, optimized nutrition, and the monitoring and appropriate management of behavioral disorders. The review also acknowledges the need for better-designed clinical studies evaluating the impact of behavioral disorders and their treatments on the natural history of IBD, utilizing hard end points to assess changes in the inflammatory process as opposed to reliance on symptom-based assessments. The findings of the review also encourage a better understanding of changes in brain function and circadian rhythm induced by intestinal inflammation.
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Affiliation(s)
- Stephen M Collins
- Farncombe Family Digestive Health Research Institute, Department of Medicine, Division of Gastroenterology, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada,Address correspondence to: Stephen M. Collins, MBBS, FRCPC, FRSC, Farncombe Family Digestive Health Research Institute, Faculty of Health Sciences, Room 3N8B, McMaster University Medical Centre, Hamilton, Ontario, CANADA L8N 3Z5. E-mail:
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12
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Kim SW, Kim S, Son M, Cheon JH, Park YS. Melatonin controls microbiota in colitis by goblet cell differentiation and antimicrobial peptide production through Toll-like receptor 4 signalling. Sci Rep 2020; 10:2232. [PMID: 32042047 PMCID: PMC7010660 DOI: 10.1038/s41598-020-59314-7] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 01/14/2020] [Indexed: 12/12/2022] Open
Abstract
Microbial dysbiosis has long been postulated to be associated with the pathogenesis of inflammatory bowel disease (IBD). Although evidence supporting the anti-colitic effects of melatonin have been accumulating, it is not clear how melatonin affects the microbiota. Herein, we investigated the effects of melatonin on the microbiome in colitis and identified involvement of Toll-like receptor (TLR) 4 signalling in the effects. Melatonin improved dextran sulfate sodium (DSS)-induced colitis and reverted microbial dysbiosis in wild-type (WT) mice but not in TLR4 knockout (KO) mice. Induction of goblet cells was observed with melatonin administration, which was accompanied by suppression of Il1b and Il17a and induction of melatonin receptor and Reg3β, an antimicrobial peptide (AMP) against Gram-negative bacteria. In vitro, melatonin treatment of HT-29 intestinal epithelial cells promotes mucin and wound healing and inhibits growth of Escherichia coli. Herein, we showed that melatonin significantly increases goblet cells, Reg3β, and the ratio of Firmicutes to Bacteriodetes by suppressing Gram-negative bacteria through TLR4 signalling. Our study suggests that sensing of bacteria through TLR4 and regulation of bacteria through altered goblet cells and AMPs is involved in the anti-colitic effects of melatonin. Melatonin may have use in therapeutics for IBD.
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Affiliation(s)
- Seung Won Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.,Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Soochan Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Mijeong Son
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.,Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.,Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Young Sook Park
- Department of Internal Medicine, Eulji Hospital, Eulji University School of Medicine, Seoul, Korea.
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13
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Rashidian A, Rashki A, Abdollahi A, Haddadi NS, Chamanara M, Mumtaz F, Dehpour AR. Dapsone reduced acetic acid-induced inflammatory response in rat colon tissue through inhibition of NF-kB signaling pathway. Immunopharmacol Immunotoxicol 2019; 41:607-613. [DOI: 10.1080/08923973.2019.1678635] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- Amir Rashidian
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Asma Rashki
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Abdollahi
- Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Nazgol-Sadat Haddadi
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Chamanara
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacology, School of Medicine, Aja University of Medical Sciences, Tehran, Iran
| | - Faiza Mumtaz
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Reza Dehpour
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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14
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Yan L, Liang M, Hou X, Zhang Y, Zhang H, Guo Z, Jinyu J, Feng Z, Mei Z. The role of microRNA-16 in the pathogenesis of autoimmune diseases: A comprehensive review. Biomed Pharmacother 2019; 112:108583. [DOI: 10.1016/j.biopha.2019.01.044] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Revised: 01/06/2019] [Accepted: 01/15/2019] [Indexed: 12/20/2022] Open
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15
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Li RX, Li J, Zhang SY, Mi YL, Zhang CQ. Attenuating effect of melatonin on lipopolysaccharide-induced chicken small intestine inflammation. Poult Sci 2018; 97:2295-2302. [PMID: 29596657 DOI: 10.3382/ps/pey084] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2017] [Indexed: 12/12/2022] Open
Abstract
Enriched melatonin (MEL) has been found in the mammalian intestine and has been recently demonstrated to alleviate rodent colitis. In this study, the effect of MEL on lipopolysaccharide (LPS)-induced intestinal inflammations was investigated in new chicken hatchlings. The chicks were fed with a diet supplemented with MEL (12.5 mg/day) from D1 to D10. Meanwhile, the chicks in the LPS or MEL + LPS groups were injected with LPS (10 mg/kg BW, i.p.) at D10. LPS treatment for 6 h increased the expression of IL-6, IL-4, caspase-3 mRNAs and TUNEL-positive cell populations, but decreased populations of the goblet and PCNA+ cells, IgA production and the expression of MUC2 mRNA in the duodenum. Compared with the LPS group, MEL pre-feeding alleviated duodenal inflammation and decreased the expression of TNF-α mRNAs by 23.6% (P = 0.004), IL-6 mRNAs by 69.4% (P = 0.001), IL-4 mRNAs by 4.1% (P = 0.824) and caspase-3 mRNAs by 45.8% (P < 0.001). Conversely, MEL pre-feeding attenuated the LPS-induced changes of IgA production by 161.6% (P = 0.013) and PCNA+ cell populations by 172.1% (P < 0.001) in the duodenum. TLR4 mRNA was also up-regulated by LPS treatment but down-regulated by MEL pre-feeding. In conclusion, dietary MEL could attenuate LPS-induced chick duodenal inflammation by down-regulating the expression of inflammatory cytokines, promoting epithelial cell proliferation, improving the immunological barrier and inhibiting epithelial apoptosis via the mediation of TLR4.
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Affiliation(s)
- R X Li
- Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
| | - J Li
- Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
| | - S Y Zhang
- Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
| | - Y L Mi
- Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
| | - C Q Zhang
- Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
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16
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Melatonin ameliorates TNBS-induced colitis in rats through the melatonin receptors: involvement of TLR4/MyD88/NF-κB signalling pathway. Inflammopharmacology 2018; 27:361-371. [PMID: 30143913 DOI: 10.1007/s10787-018-0523-8] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Accepted: 02/07/2018] [Indexed: 12/13/2022]
Abstract
AIM The aim of the present study is to investigate the anti-inflammatory effect of melatonin in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis through the inhibition of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signalling pathway and activation of melatonin receptor. METHODS Colitis was induced in Wistar rats by administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50% ethanol solution using a flexible plastic rubber catheter into the colon via the anus. This resulted in incidence of colitis on the first day, and all treatments were conducted for 10 days after induction of colitis. Melatonin was administered intraperitoneally (i.p.) at doses of 1, 5, and 10 mg/kg/day. Luzindole (non-selective MT1/MT2 receptor antagonist) was administered i.p. at dose of 5 mg/kg/day 15 min prior to melatonin injection. During the experiment, animals were monitored for the appearance of diarrhoea, body weight loss, and rectal bleeding. Myeloid peroxidase enzyme and tumour necrosis factor-α (TNF-α) activities were detected by immunohistochemistry. The protein expression level of TLR4, myeloid differentiation factor 88 (MyD88), NF-κB p65, and inhibitor of kappa B (I-κB) were detected by western blotting analysis. RESULTS Treatment with melatonin improved weight loss, mucosal, and histological damage compared with TNBS group. In addition, melatonin decreased TNBS-induced up-regulation of TLR4, MyD88, and NF-κB p65, and increased down-regulation of I-κB proteins. On the other hand, the administration of luzindole resulted in the inhibition of melatonin effects. CONCLUSIONS It seems that the inhibition of TLR4/NF-κB signalling pathway may mediate the anti-inflammatory effects of melatonin in TNBS-induced rat colitis.
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17
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Liu G, Jiang Q, Chen S, Fang J, Ren W, Yin J, Yao K, Yin Y. Melatonin alters amino acid metabolism and inflammatory responses in colitis mice. Amino Acids 2017; 49:2065-2071. [PMID: 28929336 DOI: 10.1007/s00726-017-2489-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Accepted: 09/11/2017] [Indexed: 12/21/2022]
Abstract
Inflammatory bowel disease is a chronic inflammatory dysfunction of the gastrointestinal tract. This study explored the hypothesis that melatonin has beneficial functions in the mouse model of colitis induced by dextran sodium sulfate (DSS), with a specific focus on the expression of intestinal inflammatory cytokines and the serum levels of amino acids. The results revealed that mice with melatonin supplementation had a reduction in weight loss and disease index induced by DSS treatment. Melatonin stifled the expression of colonic IL-17 in mice with DSS-induced colitis. Melatonin also lowered the serum levels of Asp, Ser, Met, and Leu (p < 0.05), but increased those of Glu and Cys (p < 0.05). Thus, melatonin treatment is promising and may function as a potential adjuvant therapy to alleviate the clinical symptoms of patients with inflammatory bowel disease.
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Affiliation(s)
- Gang Liu
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, 410125, Hunan, China
| | - Qian Jiang
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, 410125, Hunan, China
| | - Shuai Chen
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, 410125, Hunan, China
| | - Jun Fang
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, 410128, Hunan, China
| | - Wenkai Ren
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, 410125, Hunan, China.
| | - Jie Yin
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, 410125, Hunan, China
| | - Kang Yao
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, 410125, Hunan, China.
| | - Yulong Yin
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, 410125, Hunan, China.,Animal Nutrition and Human Health Laboratory, School of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China.,College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
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18
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Meng X, Li Y, Li S, Zhou Y, Gan RY, Xu DP, Li HB. Dietary Sources and Bioactivities of Melatonin. Nutrients 2017; 9:E367. [PMID: 28387721 PMCID: PMC5409706 DOI: 10.3390/nu9040367] [Citation(s) in RCA: 204] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2017] [Revised: 03/14/2017] [Accepted: 03/31/2017] [Indexed: 12/14/2022] Open
Abstract
Insomnia is a serious worldwide health threat, affecting nearly one third of the general population. Melatonin has been reported to improve sleep efficiency and it was found that eating melatonin-rich foods could assist sleep. During the last decades, melatonin has been widely identified and qualified in various foods from fungi to animals and plants. Eggs and fish are higher melatonin-containing food groups in animal foods, whereas in plant foods, nuts are with the highest content of melatonin. Some kinds of mushrooms, cereals and germinated legumes or seeds are also good dietary sources of melatonin. It has been proved that the melatonin concentration in human serum could significantly increase after the consumption of melatonin containing food. Furthermore, studies show that melatonin exhibits many bioactivities, such as antioxidant activity, anti-inflammatory characteristics, boosting immunity, anticancer activity, cardiovascular protection, anti-diabetic, anti-obese, neuroprotective and anti-aging activity. This review summaries the dietary sources and bioactivities of melatonin, with special attention paid to the mechanisms of action.
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Affiliation(s)
- Xiao Meng
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
| | - Ya Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
| | - Sha Li
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China.
| | - Yue Zhou
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
| | - Ren-You Gan
- School of Biological Sciences, The University of Hong Kong, Hong Kong 999077, China.
| | - Dong-Ping Xu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
| | - Hua-Bin Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
- South China Sea Bioresource Exploitation and Utilization Collaborative Innovation Center, Sun Yat-sen University, Guangzhou 510006, China.
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19
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Esteban-Zubero E, López-Pingarrón L, Alatorre-Jiménez MA, Ochoa-Moneo P, Buisac-Ramón C, Rivas-Jiménez M, Castán-Ruiz S, Antoñanzas-Lombarte Á, Tan DX, García JJ, Reiter RJ. Melatonin's role as a co-adjuvant treatment in colonic diseases: A review. Life Sci 2017; 170:72-81. [PMID: 27919824 DOI: 10.1016/j.lfs.2016.11.031] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 11/17/2016] [Accepted: 11/30/2016] [Indexed: 02/07/2023]
Abstract
Melatonin is produced in the pineal gland as well as many other organs, including the enterochromaffin cells of the digestive mucosa. Melatonin is a powerful antioxidant that resists oxidative stress due to its capacity to directly scavenge reactive species, to modulate the antioxidant defense system by increasing the activities of antioxidant enzymes, and to stimulate the innate immune response through its direct and indirect actions. In addition, the dysregulation of the circadian system is observed to be related with alterations in colonic motility and cell disruptions due to the modifications of clock genes expression. In the gastrointestinal tract, the activities of melatonin are mediated by melatonin receptors (MT2), serotonin (5-HT), and cholecystokinin B (CCK2) receptors and via receptor-independent processes. The levels of melatonin in the gastrointestinal tract exceed by 10-100 times the blood concentrations. Also, there is an estimated 400 times more melatonin in the gut than in the pineal gland. Gut melatonin secretion is suggested to be influenced by the food intake. Low dose melatonin treatment accelerates intestinal transit time whereas high doses may decrease gut motility. Melatonin has been studied as a co-adjuvant treatment in several gastrointestinal diseases including irritable bowel syndrome (IBS), constipation-predominant IBS (IBS-C), diarrhea-predominant IBS (IBS-D), Crohn's disease, ulcerative colitis, and necrotizing enterocolitis. The purpose of this review is to provide information regarding the potential benefits of melatonin as a co-adjuvant treatment in gastrointestinal diseases, especially IBS, Crohn's disease, ulcerative colitis, and necrotizing enterocolitis.
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Affiliation(s)
- Eduardo Esteban-Zubero
- Department of Pharmacology and Physiology, University of Zaragoza. Calle Domingo Miral s/n, 50009 Zaragoza, Spain.
| | - Laura López-Pingarrón
- Department of Medicine, Psychiatry and Dermatology, University of Zaragoza. Calle Domingo Miral s/n, 50009 Zaragoza, Spain
| | - Moisés Alejandro Alatorre-Jiménez
- Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
| | - Purificación Ochoa-Moneo
- Department of Medicine, Psychiatry and Dermatology, University of Zaragoza. Calle Domingo Miral s/n, 50009 Zaragoza, Spain
| | - Celia Buisac-Ramón
- Primary Care Unit, Sector Zaragoza III, Avenida San Juan Bosco 5, 50009 Zaragoza, Spain
| | - Miguel Rivas-Jiménez
- Department of Medicine, Psychiatry and Dermatology, University of Zaragoza. Calle Domingo Miral s/n, 50009 Zaragoza, Spain
| | - Silvia Castán-Ruiz
- Primary Care Unit, Sector Zaragoza III, Avenida San Juan Bosco 5, 50009 Zaragoza, Spain
| | - Ángel Antoñanzas-Lombarte
- Department of Medicine, Psychiatry and Dermatology, University of Zaragoza. Calle Domingo Miral s/n, 50009 Zaragoza, Spain
| | - Dun-Xian Tan
- Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
| | - José Joaquín García
- Department of Pharmacology and Physiology, University of Zaragoza. Calle Domingo Miral s/n, 50009 Zaragoza, Spain
| | - Russel J Reiter
- Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
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20
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Kim TK, Park YS, Baik HW, Jun JH, Kim EK, Sull JW, Sung HJ, Choi JW, Chung SH, Gye MC, Lim JY, Kim JB, Kim SH. Melatonin modulates adiponectin expression on murine colitis with sleep deprivation. World J Gastroenterol 2016; 22:7559-7568. [PMID: 27672276 PMCID: PMC5011669 DOI: 10.3748/wjg.v22.i33.7559] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Revised: 07/11/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation.
METHODS The following five groups of C57BL/6 mice were used in this study: (1) group I, control; (2) group II, 2% DSS induced colitis for 7 d; (3) group III, 2% DSS induced colitis and melatonin treatment; (4) group IV, 2% DSS induced colitis with sleep deprivation (SD) using specially designed and modified multiple platform water baths; and (5) group V, 2% DSS induced colitis with SD and melatonin treatment. Melatonin (10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti-adiponectin antibody. After sampling by intracardiac punctures, levels of serum cytokines were measured by ELISA.
RESULTS Sleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury, but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis, with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly (P < 0.05) recovered the expression of adiponectin. The expression levels of IL-6 and IL-17 were increased in the serum of mice with DSS colitis but decreased after melatonin injection.
CONCLUSION This study suggested that melatonin modulated adiponectin expression in colonic tissue and melatonin and adiponectin synergistically potentiated anti-inflammatory effects on colitis with sleep deprivation.
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Farez MF, Calandri IL, Correale J, Quintana FJ. Anti-inflammatory effects of melatonin in multiple sclerosis. Bioessays 2016; 38:1016-26. [DOI: 10.1002/bies.201600018] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Affiliation(s)
- Mauricio F. Farez
- Center for Research on Neuroimmunological Diseases (CIEN); Raúl Carrea Institute for Neurological Research (FLENI); Buenos Aires Argentina
- Department of Neurology; Raúl Carrea Institute for Neurological Research (FLENI); Buenos Aires Argentina
| | - Ismael L. Calandri
- Department of Neurology; Raúl Carrea Institute for Neurological Research (FLENI); Buenos Aires Argentina
| | - Jorge Correale
- Center for Research on Neuroimmunological Diseases (CIEN); Raúl Carrea Institute for Neurological Research (FLENI); Buenos Aires Argentina
- Department of Neurology; Raúl Carrea Institute for Neurological Research (FLENI); Buenos Aires Argentina
| | - Francisco J. Quintana
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital; Harvard Medical School; Boston MA USA
- The Broad Institute; Cambridge MA USA
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Pelagalli A, Squillacioti C, Mirabella N, Meli R. Aquaporins in Health and Disease: An Overview Focusing on the Gut of Different Species. Int J Mol Sci 2016; 17:1213. [PMID: 27472320 PMCID: PMC5000611 DOI: 10.3390/ijms17081213] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Revised: 07/14/2016] [Accepted: 07/14/2016] [Indexed: 12/11/2022] Open
Abstract
Aquaporins (AQPs) play a pivotal role in gut homeostasis since their distribution and function is modulated both in physiological and in pathophysiological conditions. The transport of water and solutes through gut epithelia is essential for osmoregulation and digestive and absorptive functions. This passage is regulated by different AQP isoforms and characterized by their peculiar distribution in the gastrointestinal tract. To date, AQP localization has been identified in the gut and associated organs of several mammalian species by different techniques (immunohistochemical, western blotting, and RT-PCR). The present review describes the modulation of AQP expression, distribution, and function in gut pathophysiology. At the same time, the comparative description of AQP in animal species sheds light on the full range of AQP functions and the screening of their activity as transport modulators, diagnostic biomarkers, and drug targets. Moreover, the phenotype of knockout mice for several AQPs and their compensatory role and the use of specific AQP inhibitors have been also reviewed. The reported data could be useful to design future research in both basic and clinical fields.
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Affiliation(s)
- Alessandra Pelagalli
- Department of Advanced Biomedical Sciences, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy.
- Institute of Biostructures and Bioimages, National Research Council, Via De Amicis 95, 80131 Naples, Italy.
| | - Caterina Squillacioti
- Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II", Via Veterinaria 1, 80137 Naples, Italy.
| | - Nicola Mirabella
- Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II", Via Veterinaria 1, 80137 Naples, Italy.
| | - Rosaria Meli
- Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131 Naples, Italy.
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Zielińska M, Jarmuż A, Sałaga M, Kordek R, Laudon M, Storr M, Fichna J. Melatonin, but not melatonin receptor agonists Neu-P11 and Neu-P67, attenuates TNBS-induced colitis in mice. Naunyn Schmiedebergs Arch Pharmacol 2016; 389:511-9. [PMID: 26899972 PMCID: PMC4823353 DOI: 10.1007/s00210-016-1214-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Accepted: 01/25/2016] [Indexed: 12/28/2022]
Abstract
Melatonin is known as a strong antioxidant and possesses anti-inflammatory properties. Recently, melatonin was shown to improve colitis in animal models of inflammatory bowel diseases. The aim of the present study was to characterize the role of melatonin receptors (MT) in the anti-inflammatory effect of melatonin and to assess the anti-inflammatory potential of two novel MT receptor agonists, Neu-P11 and Neu-P67, in the mouse model of trinitrobenzenesulfonic acid (TNBS)-induced colitis. Colitis was induced on day 1 by intracolonic (i.c.) administration of TNBS in 30 % ethanol in saline. Melatonin (4 mg/kg, per os (p.o.)), Neu-P11 (20 mg/kg, p.o.; 50 mg/kg, intraperitoneally (i.p.), 50 mg/kg, i.c.), and Neu-P67 (20 mg/kg, p.o.) were given twice daily for 3 days. Luzindole (5 mg/kg, i.p.) was injected 15 min prior to melatonin administration. On day 4, macroscopic and microscopic damage scores were assessed and myeloperoxidase (MPO) activity quantified using O-dianisidine-based assay. Melatonin significantly attenuated colitis in mice, as indicated by the macroscopic score (1.90 ± 0.34 vs. 3.82 ± 0.62 for melatonin- and TNBS-treated mice, respectively), ulcer score (0.87 ± 0.18 vs. 1.31 ± 0.19, respectively), and MPO activity (4.68 ± 0.70 vs.6.26 ± 0.94, respectively). Luzindole, a MT receptor antagonist, did not inhibit the anti-inflammatory effect of melatonin (macroscopic score 1.12 ± 0.22, ulcer score 0.50 ± 0.16); however, luzindole increased MPO activity (7.57 ± 1.05). MT receptor agonists Neu-P11 and Neu-P67 did not improve inflammation induced by TNBS. Melatonin, but not MT receptor agonists, exerts potent anti-inflammatory action in acute TNBS-induced colitis. Our data suggests that melatonin attenuates colitis by additional, MT receptor-independent pathways.
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Affiliation(s)
- Marta Zielińska
- Department of Biochemistry, Medical University of Lodz, Lodz, Poland
| | - Agata Jarmuż
- Department of Biochemistry, Medical University of Lodz, Lodz, Poland
| | - Maciej Sałaga
- Department of Biochemistry, Medical University of Lodz, Lodz, Poland
| | - Radzisław Kordek
- Department of Pathology, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | | | - Martin Storr
- Walter Brendel Center of Experimental Medicine, University of Munich, Munich, Germany
- Department of Medicine, Division of Gastroenterology, Ludwig Maximilians University of Munich, Munich, Germany
| | - Jakub Fichna
- Department of Biochemistry, Medical University of Lodz, Lodz, Poland.
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Calvo J, Maldonado M. The role of melatonin in autoimmune and atopic diseases. AIMS MOLECULAR SCIENCE 2016. [DOI: 10.3934/molsci.2016.2.158] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
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Szewczyk-Golec K, Woźniak A, Reiter RJ. Inter-relationships of the chronobiotic, melatonin, with leptin and adiponectin: implications for obesity. J Pineal Res 2015; 59:277-91. [PMID: 26103557 DOI: 10.1111/jpi.12257] [Citation(s) in RCA: 103] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Accepted: 06/19/2015] [Indexed: 12/15/2022]
Abstract
Obesity and its medical complications represent a significant problem throughout the world. In recent decades, mechanisms underlying the progression of obesity have been intensively examined. The involvement of both the behavioral aspects, such as calorie-rich diet, low physical activity and sleep deprivation, and the intrinsic factors, including adipose tissue deregulation, chronic inflammation, oxidative stress, and chronodisruption, has been identified. The circadian disturbances of the adipose tissue endocrine function have been correlated with obesity. Leptin and adiponectin are adipokines strongly associated with glucose and lipid metabolism and with energy balance. Their synthesis and secretion display circadian rhythms that are disturbed in the obese state. Hyperleptinemia resulting in leptin resistance, and hypo-adiponectinemia have been linked to the pathophysiology of the obesity-related disorders. A deficiency of melatonin, one of the consequences of sleep deprivation, has also been demonstrated to correlate with obesity. Melatonin is a pineal secretory product involved in numerous actions, such as regulation of internal biological clocks and energy metabolism, and it functions as an antioxidant and as an anti-inflammatory agent. There exists a substantial amount of evidence supporting the beneficial effects of melatonin supplementation on obesity and its complications. In the current review, the results of studies related to the interactions between melatonin, and both leptin and adiponectin are discussed. Despite the existence of some inconsistencies, melatonin has been found to normalize the expression and secretion patterns of both adipokines. These results support the concept of melatonin as a potential therapeutic agent for obesity and related disorders.
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Affiliation(s)
- Karolina Szewczyk-Golec
- The Chair of Medical Biology, Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum, Bydgoszcz, Poland
| | - Alina Woźniak
- The Chair of Medical Biology, Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum, Bydgoszcz, Poland
| | - Russel J Reiter
- Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA
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Abstract
BACKGROUND Current understanding of the onset of inflammatory bowel diseases relies heavily on data derived from animal models of colitis. However, the omission of information concerning the method used makes the interpretation of studies difficult or impossible. We assessed the current quality of methods reporting in 4 animal models of colitis that are used to inform clinical research into inflammatory bowel disease: dextran sulfate sodium, interleukin-10, CD45RB T cell transfer, and 2,4,6-trinitrobenzene sulfonic acid (TNBS). METHODS We performed a systematic review based on PRISMA guidelines, using a PubMed search (2000-2014) to obtain publications that used a microarray to describe gene expression in colitic tissue. Methods reporting quality was scored against a checklist of essential and desirable criteria. RESULTS Fifty-eight articles were identified and included in this review (29 dextran sulfate sodium, 15 interleukin-10, 5 T cell transfer, and 16 TNBS; some articles use more than 1 colitis model). A mean of 81.7% (SD = ±7.038) of criteria were reported across all models. Only 1 of the 58 articles reported all essential criteria on our checklist. Animal age, gender, housing conditions, and mortality/morbidity were all poorly reported. CONCLUSIONS Failure to include all essential criteria is a cause for concern; this failure can have large impact on the quality and replicability of published colitis experiments. We recommend adoption of our checklist as a requirement for publication to improve the quality, comparability, and standardization of colitis studies and will make interpretation and translation of data to human disease more reliable.
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Overexpression of circadian clock protein cryptochrome (CRY) 1 alleviates sleep deprivation-induced vascular inflammation in a mouse model. Immunol Lett 2014; 163:76-83. [PMID: 25435215 DOI: 10.1016/j.imlet.2014.11.014] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2014] [Revised: 11/20/2014] [Accepted: 11/22/2014] [Indexed: 12/11/2022]
Abstract
Disturbance of the circadian clock by sleep deprivation has been proposed to be involved in the regulation of inflammation. However, the underlying mechanism of circadian oscillator components in regulating the pro-inflammatory process during sleep deprivation remains poorly understood. Using a sleep deprivation mouse model, we showed here that sleep deprivation increased the expression of pro-inflammatory cytokines expression and decreased the expression of cryptochrome 1 (CRY1) in vascular endothelial cells. Furthermore, the adhesion molecules including intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin were elevated in vascular endothelial cells and the monocytes binding to vascular endothelial cells were also increased by sleep deprivation. Interestingly, overexpression of CRY1 in a mouse model by adenovirus vector significantly inhibited the expression of inflammatory cytokines and adhesion molecules, and NF-κB signal pathway activation, as well as the binding of monocytes to vascular endothelial cells. Using a luciferase reporter assay, we found that CRY1 could repress the transcriptional activity of nuclear factor (NF)-κB in vitro. Subsequently, we demonstrated that overexpression of CRY1 inhibited the basal concentration of cyclic adenosine monophosphate (cAMP), leading to decreased protein kinase A activity, which resulted in decreased phosphorylation of p65. Taken together, these results suggested that the overexpression of CRY1 inhibited sleep deprivation-induced vascular inflammation that might be associated with NF-κB and cAMP/PKA pathways.
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