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Melatonin ameliorates lipopolysaccharide induced brain inflammation through modulation of oxidative status and diminution of cytokine rush in Danio rerio
Affiliation:1. Department of Zoology, University of Calcutta, Kolkata 700019, India;2. Department of Zoology, University of North Bengal, Darjeeling 734013, India;3. Department of Physiology, Medical College and Hospital, Kolkata, India;4. Fisheries and Ecotoxicology Research Laboratory Vice Chancellor’s Research Group, Department of Zoology, The University of Burdwan, Purba bardhaman, Burdwan 713104, West Bengal, India;1. Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA 52242, United States;2. Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, United States;3. IIHR Hydroscience and Engineering, The University of Iowa, Iowa City, IA 52242, United States;4. Department of Civil and Environmental Engineering, The University of Iowa, Iowa City, IA 52242, United States;5. Center for Health Effects of Environmental Contamination, The University of Iowa, Iowa City, IA 52242;1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, USA;2. Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA, USA;3. Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, CA, USA;4. Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA;5. Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO, USA;6. Department of Medicine, University of California, San Diego, La Jolla, CA, USA;7. Heart and Vascular Institute, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, USA;1. Academic of Chemical Engineering, Universidade Tecnológica Federal do Paraná (UTFPR), Campus Francisco Beltrão, Paraná, Brazil;2. Academic Department of Agricultural Sciences, Universidade Tecnológica Federal do Paraná (UTFPR), Campus Francisco Beltrão, Francisco Beltrão, Paraná, Brazil;3. Academic Department of Physics, Statistics and Mathematics, Universidade Tecnológica Federal do Paraná (UTFPR), Francisco Beltrão, Paraná, Brazil;4. Academic Department of Engineering, Universidade Tecnológica Federal do Paraná (UTFPR), Campus Francisco Beltrão, Francisco Beltrão, Paraná, Brazil;5. Academic Department of Chemistry and Biology, Universidade Tecnológica Federal do Paraná (UTFPR), Campus Francisco Beltrão, Paraná, Brazil;1. Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok Thailand;2. Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok Thailand;1. Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey;2. Betül-Ziya Eren Genome and Stem Cell Center, Erciyes University, Kayseri, Turkey;3. Department of Medical Biology, Faculty of Medicine, Erciyes University, Kayseri, Turkey;4. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden;5. Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey;1. Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University, Im Neuenheimer Feld 329, 69120 Heidelberg, Germany;2. A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio 70211, Finland;3. Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio 70211, Finland;4. School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland
Abstract:Lipopolysaccharide (LPS) is known to induce inflammation and immunonomodulation in a piscine model of Danio rerio. Present study aimed to explore the ability of melatonin in attenuating LPS-induced oxidative damages using this model. In LPS-exposed fish, activation of stress marker MDA was observed in brain with corresponding augmentation of multiple pro-inflammatory cytokines (IL1β, IL6, IL10 and TNFα). In addition, it also showed marked increase in the levels of heat shock factor (HSF) and heat shock proteins (HSPs) in association with transcription factors (NF-kB and NRF2) and mitogen-activated protein kinases (MAPKs). The changes in the levels of these mediators are highly correlated with the induction of pro-inflammatory cytokines. In melatonin-treated fishes, significant amelioration of oxidative stress was observed with reduced levels of MDA and pro-inflammatory cytokines. Melatonin also modulated expression of HSPs that facilitated the brain to overcome inflammation-induced stress by directly initiating NFkB/NRF2 translocation. In summary, melatonin effectively functions to reduce stress induced inflammatory signalling through modulation of oxidative stress and protects the brain from the neuropathological insult.
Keywords:Melatonin  Inflammation  Cytokines  Molecular chaperones  Lipopolysaccharide
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