A model of alcoholic liver disease based on different hepatotoxics leading to liver cancer
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved..
The worst-case scenario related to alcoholic liver disease (ALD) arises after a long period of exposure to the harmful effect of alcohol consumption along with other hepatotoxics. ALD encompasses a broad spectrum of liver-associated disorders, such as steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Based on the chronic administration of different hepatotoxics, including ethanol, sucrose, lipopolysaccharide, and low doses of diethylnitrosamine over a short period, here we aimed to develop a multiple hepatotoxic (MHT)-ALD model in the mouse that recapitulates the human ALD-associated disorders. We demonstrated that the MHT-ALD model induces ADH1A and NXN, an ethanol metabolizer and a redox-sensor enzyme, respectively; promotes steatosis associated with the induction of the lipid droplet forming FSP27, inflammation identified by the infiltration of hepatic neutrophils-positive to LY-6G marker, and the increase of MYD88 level, a protein involved in inflammatory response; and stimulates the early appearance of cellular senescence identified by the senescence markers SA-β-gal activity and p-H2A.XSer139. It also induces fibrosis associated with increased desmin, a marker of hepatic stellate cells whose activation leads to the deposition of collagen fibers, accompanied by cell death and compensatory proliferation revealed by increased CASP3-mediated apoptosis, and KI67- and PCNA-proliferation markers, respectively. It also induces histopathological traits of malignancy and the level of the HCC marker, GSTP1. In conclusion, we provide a useful model for exploring the chronological ALD-associated alterations and stages, and addressing therapeutic approaches.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Biochemical pharmacology - (2024) vom: 16. Apr., Seite 116209 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Alarcón-Sánchez, Brisa Rodope [VerfasserIn] |
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| Links: |
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| Themen: |
Alcohol consumption |
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| Anmerkungen: |
Date Revised 17.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.bcp.2024.116209 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM371105528 |
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| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a The worst-case scenario related to alcoholic liver disease (ALD) arises after a long period of exposure to the harmful effect of alcohol consumption along with other hepatotoxics. ALD encompasses a broad spectrum of liver-associated disorders, such as steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Based on the chronic administration of different hepatotoxics, including ethanol, sucrose, lipopolysaccharide, and low doses of diethylnitrosamine over a short period, here we aimed to develop a multiple hepatotoxic (MHT)-ALD model in the mouse that recapitulates the human ALD-associated disorders. We demonstrated that the MHT-ALD model induces ADH1A and NXN, an ethanol metabolizer and a redox-sensor enzyme, respectively; promotes steatosis associated with the induction of the lipid droplet forming FSP27, inflammation identified by the infiltration of hepatic neutrophils-positive to LY-6G marker, and the increase of MYD88 level, a protein involved in inflammatory response; and stimulates the early appearance of cellular senescence identified by the senescence markers SA-β-gal activity and p-H2A.XSer139. It also induces fibrosis associated with increased desmin, a marker of hepatic stellate cells whose activation leads to the deposition of collagen fibers, accompanied by cell death and compensatory proliferation revealed by increased CASP3-mediated apoptosis, and KI67- and PCNA-proliferation markers, respectively. It also induces histopathological traits of malignancy and the level of the HCC marker, GSTP1. In conclusion, we provide a useful model for exploring the chronological ALD-associated alterations and stages, and addressing therapeutic approaches | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Alcohol consumption | |
| 650 | 4 | |a Animal model | |
| 650 | 4 | |a Cellular senescence | |
| 650 | 4 | |a Diethylnitrosamine | |
| 650 | 4 | |a Lipopolysaccharide | |
| 650 | 4 | |a Sucrose | |
| 700 | 1 | |a Idelfonso-García, Osiris Germán |e verfasserin |4 aut | |
| 700 | 1 | |a Guerrero-Escalera, Dafne |e verfasserin |4 aut | |
| 700 | 1 | |a Piña-Vázquez, Carolina |e verfasserin |4 aut | |
| 700 | 1 | |a de Anda-Jáuregui, Guillermo |e verfasserin |4 aut | |
| 700 | 1 | |a Pérez-Hernández, José Luis |e verfasserin |4 aut | |
| 700 | 1 | |a de la Garza, Mireya |e verfasserin |4 aut | |
| 700 | 1 | |a García-Sierra, Francisco |e verfasserin |4 aut | |
| 700 | 1 | |a Sánchez-Pérez, Yesennia |e verfasserin |4 aut | |
| 700 | 1 | |a Baltiérrez-Hoyos, Rafael |e verfasserin |4 aut | |
| 700 | 1 | |a Vásquez-Garzón, Verónica Rocío |e verfasserin |4 aut | |
| 700 | 1 | |a Muriel, Pablo |e verfasserin |4 aut | |
| 700 | 1 | |a Pérez-Carreón, Julio Isael |e verfasserin |4 aut | |
| 700 | 1 | |a Villa-Treviño, Saúl |e verfasserin |4 aut | |
| 700 | 1 | |a Arellanes-Robledo, Jaime |e verfasserin |4 aut | |
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