Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Brol, Maximilian Joseph UNSPECIFIED UNSPECIFIED UNSPECIFIED Roesch, Felicitas UNSPECIFIED UNSPECIFIED UNSPECIFIED Schierwagen, Robert UNSPECIFIED orcid.org/0000-0002-2195-3666 UNSPECIFIED Magdaleno, Fernando UNSPECIFIED UNSPECIFIED UNSPECIFIED Uschner, Frank Erhard UNSPECIFIED orcid.org/0000-0002-3760-2887 UNSPECIFIED Manekeller, Steffen UNSPECIFIED UNSPECIFIED UNSPECIFIED Queck, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarzkopf, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Odenthal, Margarete UNSPECIFIED UNSPECIFIED UNSPECIFIED Drebber, Uta UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Maja UNSPECIFIED orcid.org/0000-0003-1854-1924 UNSPECIFIED Lingohr, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Plamper, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Kristiansen, Glen UNSPECIFIED UNSPECIFIED UNSPECIFIED Lotersztajn, Sophie UNSPECIFIED UNSPECIFIED UNSPECIFIED Krag, Aleksander UNSPECIFIED orcid.org/0000-0002-9598-4932 UNSPECIFIED Klein, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Rheinwalt, Karl P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Trebicka, Jonel UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language MODEL; MICE; STEATOSIS Multiple languages Gastroenterology & Hepatology; Physiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13382