Establishment of the tree shrew as an alcohol-induced Fatty liver model for the study of alcoholic liver diseases

Currently, the pathogenesis of alcoholic liver diseases (ALDs) is not clear. As a result, there is no effective treatment for ALDs. One limitation is the lack of a suitable animal model for use in studying ALDs. The tree shrew is a lower primate animal, characterized by a high-alcohol diet. This wor...

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Veröffentlicht in:PloS one 2015-06, Vol.10 (6), p.e0128253-e0128253
Hauptverfasser: Xing, Huijie, Jia, Kun, He, Jun, Shi, Changzheng, Fang, Meixia, Song, Linliang, Zhang, Pu, Zhao, Yue, Fu, Jiangnan, Li, Shoujun
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container_title PloS one
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creator Xing, Huijie
Jia, Kun
He, Jun
Shi, Changzheng
Fang, Meixia
Song, Linliang
Zhang, Pu
Zhao, Yue
Fu, Jiangnan
Li, Shoujun
description Currently, the pathogenesis of alcoholic liver diseases (ALDs) is not clear. As a result, there is no effective treatment for ALDs. One limitation is the lack of a suitable animal model for use in studying ALDs. The tree shrew is a lower primate animal, characterized by a high-alcohol diet. This work aimed to establish a fatty liver model using tree shrews and to assess the animals' suitability for the study of ALDs. Tree shrews were treated with alcohol solutions (10% and 20%) for two weeks. Hemophysiology, blood alcohol concentrations (BACs), oxidative stress factors, alcohol metabolic enzymes and hepatic pathology were checked and assayed with an automatic biochemical analyzer, enzyme-linked immunosorbent assay (ELISA), western blot, hematoxylin-eosin (HE) staining and oil red O staining, and magnetic resonance imaging (MRI). Compared with the normal group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total cholesterol (TC), triglyceride (TG), reactive oxygen species (ROS), and malondialdehyde (MDA) were significantly enhanced in alcohol-treated tree shrews. However, the activity of reduced glutathione hormone (GSH) and superoxide dismutase (SOD) declined. Notable changes in alcohol dehydrogenase(ADH1), aldehyde dehydrogenase(ALDH2), CYP2E1, UDP-glucuronosyl transferase 1A1 (UGT1A1) and nuclear factor erythroid-related factor 2 (Nrf2) were observed. HE and oil red O staining showed that hepatocyte swelling, hydropic degeneration, and adipohepatic syndrome occurred in the tree shrews. Alcohol can induce fatty liver-like pathological changes and result in alterations in liver function, oxidative stress factors, alcohol metabolism enzymes and Nrf2. Therefore, the established fatty liver model of tree shrews induced by alcohol should be a promising tool for the study of ALDs.
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As a result, there is no effective treatment for ALDs. One limitation is the lack of a suitable animal model for use in studying ALDs. The tree shrew is a lower primate animal, characterized by a high-alcohol diet. This work aimed to establish a fatty liver model using tree shrews and to assess the animals' suitability for the study of ALDs. Tree shrews were treated with alcohol solutions (10% and 20%) for two weeks. Hemophysiology, blood alcohol concentrations (BACs), oxidative stress factors, alcohol metabolic enzymes and hepatic pathology were checked and assayed with an automatic biochemical analyzer, enzyme-linked immunosorbent assay (ELISA), western blot, hematoxylin-eosin (HE) staining and oil red O staining, and magnetic resonance imaging (MRI). Compared with the normal group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total cholesterol (TC), triglyceride (TG), reactive oxygen species (ROS), and malondialdehyde (MDA) were significantly enhanced in alcohol-treated tree shrews. However, the activity of reduced glutathione hormone (GSH) and superoxide dismutase (SOD) declined. Notable changes in alcohol dehydrogenase(ADH1), aldehyde dehydrogenase(ALDH2), CYP2E1, UDP-glucuronosyl transferase 1A1 (UGT1A1) and nuclear factor erythroid-related factor 2 (Nrf2) were observed. HE and oil red O staining showed that hepatocyte swelling, hydropic degeneration, and adipohepatic syndrome occurred in the tree shrews. Alcohol can induce fatty liver-like pathological changes and result in alterations in liver function, oxidative stress factors, alcohol metabolism enzymes and Nrf2. Therefore, the established fatty liver model of tree shrews induced by alcohol should be a promising tool for the study of ALDs.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0128253</identifier><identifier>PMID: 26030870</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alanine ; Alanine transaminase ; Alcohol ; Alcohol dehydrogenase ; Alcohol Drinking - adverse effects ; Alcohol use ; Alcoholic beverages ; Aldehyde dehydrogenase ; Animal diseases ; Animals ; Aspartate aminotransferase ; Biomedical research ; Biotechnology ; Care and treatment ; Cholesterol ; Cytochrome P-450 ; Degeneration ; Dehydrogenase ; Dehydrogenases ; Disease Models, Animal ; Disease prevention ; Enzyme-linked immunosorbent assay ; Enzymes ; Ethanol ; Fatty liver ; Feasibility Studies ; g-Glutamyltransferase ; Gene Expression Regulation - drug effects ; Glutathione ; Hepatology ; Histopathology ; Laboratory animals ; Lipid peroxidation ; Liver ; Liver - drug effects ; Liver - metabolism ; Liver - pathology ; Liver - physiopathology ; Liver cancer ; Liver cirrhosis ; Liver diseases ; Liver Diseases, Alcoholic - etiology ; Liver Diseases, Alcoholic - metabolism ; Liver Diseases, Alcoholic - pathology ; Liver Diseases, Alcoholic - physiopathology ; Magnetic resonance ; Magnetic resonance imaging ; Male ; Malondialdehyde ; Medical research ; Metabolism ; Metabolites ; NF-E2-Related Factor 2 - metabolism ; Oils &amp; fats ; Oxidative metabolism ; Oxidative stress ; Oxidative Stress - drug effects ; Oxygen ; Pathogenesis ; Physiological aspects ; Protein expression ; Proteins ; Reactive oxygen species ; Rodents ; Soricidae ; Staining ; Superoxide dismutase ; Superoxides ; Triglycerides ; Tupaiidae ; Veterinary colleges ; Veterinary medicine ; γ-Glutamyltransferase</subject><ispartof>PloS one, 2015-06, Vol.10 (6), p.e0128253-e0128253</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Xing et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Xing et al 2015 Xing et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-6f1252e813f3acb1c030ad7a198ffce8a04fc712a90e3a54a40db3354a92ded33</citedby><cites>FETCH-LOGICAL-c758t-6f1252e813f3acb1c030ad7a198ffce8a04fc712a90e3a54a40db3354a92ded33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451149/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451149/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26030870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Feng, Wenke</contributor><creatorcontrib>Xing, Huijie</creatorcontrib><creatorcontrib>Jia, Kun</creatorcontrib><creatorcontrib>He, Jun</creatorcontrib><creatorcontrib>Shi, Changzheng</creatorcontrib><creatorcontrib>Fang, Meixia</creatorcontrib><creatorcontrib>Song, Linliang</creatorcontrib><creatorcontrib>Zhang, Pu</creatorcontrib><creatorcontrib>Zhao, Yue</creatorcontrib><creatorcontrib>Fu, Jiangnan</creatorcontrib><creatorcontrib>Li, Shoujun</creatorcontrib><title>Establishment of the tree shrew as an alcohol-induced Fatty liver model for the study of alcoholic liver diseases</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Currently, the pathogenesis of alcoholic liver diseases (ALDs) is not clear. As a result, there is no effective treatment for ALDs. One limitation is the lack of a suitable animal model for use in studying ALDs. The tree shrew is a lower primate animal, characterized by a high-alcohol diet. This work aimed to establish a fatty liver model using tree shrews and to assess the animals' suitability for the study of ALDs. Tree shrews were treated with alcohol solutions (10% and 20%) for two weeks. Hemophysiology, blood alcohol concentrations (BACs), oxidative stress factors, alcohol metabolic enzymes and hepatic pathology were checked and assayed with an automatic biochemical analyzer, enzyme-linked immunosorbent assay (ELISA), western blot, hematoxylin-eosin (HE) staining and oil red O staining, and magnetic resonance imaging (MRI). Compared with the normal group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total cholesterol (TC), triglyceride (TG), reactive oxygen species (ROS), and malondialdehyde (MDA) were significantly enhanced in alcohol-treated tree shrews. However, the activity of reduced glutathione hormone (GSH) and superoxide dismutase (SOD) declined. Notable changes in alcohol dehydrogenase(ADH1), aldehyde dehydrogenase(ALDH2), CYP2E1, UDP-glucuronosyl transferase 1A1 (UGT1A1) and nuclear factor erythroid-related factor 2 (Nrf2) were observed. HE and oil red O staining showed that hepatocyte swelling, hydropic degeneration, and adipohepatic syndrome occurred in the tree shrews. Alcohol can induce fatty liver-like pathological changes and result in alterations in liver function, oxidative stress factors, alcohol metabolism enzymes and Nrf2. 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Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xing, Huijie</au><au>Jia, Kun</au><au>He, Jun</au><au>Shi, Changzheng</au><au>Fang, Meixia</au><au>Song, Linliang</au><au>Zhang, Pu</au><au>Zhao, Yue</au><au>Fu, Jiangnan</au><au>Li, Shoujun</au><au>Feng, Wenke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Establishment of the tree shrew as an alcohol-induced Fatty liver model for the study of alcoholic liver diseases</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-06-01</date><risdate>2015</risdate><volume>10</volume><issue>6</issue><spage>e0128253</spage><epage>e0128253</epage><pages>e0128253-e0128253</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Currently, the pathogenesis of alcoholic liver diseases (ALDs) is not clear. As a result, there is no effective treatment for ALDs. One limitation is the lack of a suitable animal model for use in studying ALDs. The tree shrew is a lower primate animal, characterized by a high-alcohol diet. This work aimed to establish a fatty liver model using tree shrews and to assess the animals' suitability for the study of ALDs. Tree shrews were treated with alcohol solutions (10% and 20%) for two weeks. Hemophysiology, blood alcohol concentrations (BACs), oxidative stress factors, alcohol metabolic enzymes and hepatic pathology were checked and assayed with an automatic biochemical analyzer, enzyme-linked immunosorbent assay (ELISA), western blot, hematoxylin-eosin (HE) staining and oil red O staining, and magnetic resonance imaging (MRI). Compared with the normal group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total cholesterol (TC), triglyceride (TG), reactive oxygen species (ROS), and malondialdehyde (MDA) were significantly enhanced in alcohol-treated tree shrews. However, the activity of reduced glutathione hormone (GSH) and superoxide dismutase (SOD) declined. Notable changes in alcohol dehydrogenase(ADH1), aldehyde dehydrogenase(ALDH2), CYP2E1, UDP-glucuronosyl transferase 1A1 (UGT1A1) and nuclear factor erythroid-related factor 2 (Nrf2) were observed. HE and oil red O staining showed that hepatocyte swelling, hydropic degeneration, and adipohepatic syndrome occurred in the tree shrews. Alcohol can induce fatty liver-like pathological changes and result in alterations in liver function, oxidative stress factors, alcohol metabolism enzymes and Nrf2. Therefore, the established fatty liver model of tree shrews induced by alcohol should be a promising tool for the study of ALDs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26030870</pmid><doi>10.1371/journal.pone.0128253</doi><oa>free_for_read</oa></addata></record>
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subjects Alanine
Alanine transaminase
Alcohol
Alcohol dehydrogenase
Alcohol Drinking - adverse effects
Alcohol use
Alcoholic beverages
Aldehyde dehydrogenase
Animal diseases
Animals
Aspartate aminotransferase
Biomedical research
Biotechnology
Care and treatment
Cholesterol
Cytochrome P-450
Degeneration
Dehydrogenase
Dehydrogenases
Disease Models, Animal
Disease prevention
Enzyme-linked immunosorbent assay
Enzymes
Ethanol
Fatty liver
Feasibility Studies
g-Glutamyltransferase
Gene Expression Regulation - drug effects
Glutathione
Hepatology
Histopathology
Laboratory animals
Lipid peroxidation
Liver
Liver - drug effects
Liver - metabolism
Liver - pathology
Liver - physiopathology
Liver cancer
Liver cirrhosis
Liver diseases
Liver Diseases, Alcoholic - etiology
Liver Diseases, Alcoholic - metabolism
Liver Diseases, Alcoholic - pathology
Liver Diseases, Alcoholic - physiopathology
Magnetic resonance
Magnetic resonance imaging
Male
Malondialdehyde
Medical research
Metabolism
Metabolites
NF-E2-Related Factor 2 - metabolism
Oils & fats
Oxidative metabolism
Oxidative stress
Oxidative Stress - drug effects
Oxygen
Pathogenesis
Physiological aspects
Protein expression
Proteins
Reactive oxygen species
Rodents
Soricidae
Staining
Superoxide dismutase
Superoxides
Triglycerides
Tupaiidae
Veterinary colleges
Veterinary medicine
γ-Glutamyltransferase
title Establishment of the tree shrew as an alcohol-induced Fatty liver model for the study of alcoholic liver diseases
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