Brol, Maximilian Joseph, Roesch, Felicitas, Schierwagen, Robert ORCID: 0000-0002-2195-3666, Magdaleno, Fernando, Uschner, Frank Erhard ORCID: 0000-0002-3760-2887, Manekeller, Steffen, Queck, Alexander, Schwarzkopf, Katharina, Odenthal, Margarete, Drebber, Uta, Thiele, Maja ORCID: 0000-0003-1854-1924, Lingohr, Philipp, Plamper, Andreas, Kristiansen, Glen, Lotersztajn, Sophie, Krag, Aleksander ORCID: 0000-0002-9598-4932, Klein, Sabine, Rheinwalt, Karl P. and Trebicka, Jonel (2019). Combination of CCl4 with alcoholic and metabolic injuries mimics human liver fibrosis. Am. J. Physiol.-Gastroint. Liver Physiol., 317 (2). S. G182 - 13. BETHESDA: AMER PHYSIOLOGICAL SOC. ISSN 1522-1547

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Abstract

Metabolic and alcoholic liver injuries result in nonalcoholic (NAFLD) or alcoholic (ALD) fatty liver disease, respectively. In particular, presence of fibrosis in (NAFLD) and (ALD) requires treatment, but development of drugs is hampered by the lack of suitable models with significant fibrosis. The carbon tetrachloride (CCl4) liver fibrosis model does not reflect human NAFLD or ALD, but CCl4 may serve as a fibrosis accelerator in addition to another injury. Ethanol in drinking water (16%) or Western diet (WD) were administered for 7 wk in mice either alone or in combination with CCl4 intoxications. Extent of fibrosis. steatosis, and inflammation was assessed by histology, transcription, and biochemistry. Furthermore, transcription of fibrosis, proliferation, and inflammation-related genes was studied on human liver samples with fibrosis resulting from hepatitis C virus infection (n = 7), NAFLD (n = 8), or ALD (n = 7). WD or ethanol alone induced only mild steatosis and inflammation. Combination of CCl4 and WD induced the most severe steatosis together with significant liver fibrosis and moderate inflammation. Combination of CCl4 and ethanol induced the strongest inflammation, with significant liver fibrosis and moderate steatosis. The relationship pattern between fibrosis, proliferation, and inflammation of human ALD was mostly similar in mice treated with CCl4 and ethanol. The combination of CCl4 intoxication with WD validates previous data suggesting it as an appropriate model for human nonalcoholic steato-hepatitis. Especially, CCl4 plus ethanol for 7 wk induces ALD in mice, providing a model suitable for further basic research and drug testing. NEW & NOTEWORTHY Alcoholic fatty liver disease with significant fibrosis is generated within 7 wk using carbon tetrachloride as a fibrosis accelerator and administering gradually ethanol (up to 16%) in mice. The similarity in the pattern of steatosis, inflammation, and fibrosis involved in alcoholic fatty liver disease to those of the human condition renders this mouse model suitable as a preclinical model for drug development.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Brol, Maximilian JosephUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roesch, FelicitasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schierwagen, RobertUNSPECIFIEDorcid.org/0000-0002-2195-3666UNSPECIFIED
Magdaleno, FernandoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Uschner, Frank ErhardUNSPECIFIEDorcid.org/0000-0002-3760-2887UNSPECIFIED
Manekeller, SteffenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Queck, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwarzkopf, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Odenthal, MargareteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drebber, UtaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, MajaUNSPECIFIEDorcid.org/0000-0003-1854-1924UNSPECIFIED
Lingohr, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Plamper, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kristiansen, GlenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lotersztajn, SophieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krag, AleksanderUNSPECIFIEDorcid.org/0000-0002-9598-4932UNSPECIFIED
Klein, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rheinwalt, Karl P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trebicka, JonelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-133826
DOI: 10.1152/ajpgi.00361.2018
Journal or Publication Title: Am. J. Physiol.-Gastroint. Liver Physiol.
Volume: 317
Number: 2
Page Range: S. G182 - 13
Date: 2019
Publisher: AMER PHYSIOLOGICAL SOC
Place of Publication: BETHESDA
ISSN: 1522-1547
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MODEL; MICE; STEATOSISMultiple languages
Gastroenterology & Hepatology; PhysiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13382

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