A model of alcoholic liver disease based on different hepatotoxics leading to liver cancer.

Autor: Alarcón-Sánchez BR; Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute - CINVESTAV-IPN, Mexico City, Mexico; Laboratory of Liver Diseases, National Institute of Genomic Medicine - INMEGEN, Mexico City, Mexico. Electronic address: brisa.alarcon@cinvestav.mx., Idelfonso-García OG; Laboratory of Liver Diseases, National Institute of Genomic Medicine - INMEGEN, Mexico City, Mexico., Guerrero-Escalera D; Laboratory of Liver Diseases, National Institute of Genomic Medicine - INMEGEN, Mexico City, Mexico., Piña-Vázquez C; Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute - CINVESTAV-IPN, Mexico City, Mexico., de Anda-Jáuregui G; Computational Genomics Division, National Institute of Genomic Medicine - INMEGEN, Mexico City, Mexico; Deputy Directorate of Humanistic and Scientific Research, National Council of Humanities, Sciences and Technologies - CONAHCYT, Mexico City, Mexico., Pérez-Hernández JL; Department of Gastroenterology and Hepatology, General Hospital of Mexico 'Dr. Eduardo Liceaga', Mexico City, Mexico., de la Garza M; Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute - CINVESTAV-IPN, Mexico City, Mexico., García-Sierra F; Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute - CINVESTAV-IPN, Mexico City, Mexico., Sánchez-Pérez Y; Subdirección de Investigación Básica, Instituto Nacional de Cancerología - INCan, Mexico City, Mexico., Baltiérrez-Hoyos R; Deputy Directorate of Humanistic and Scientific Research, National Council of Humanities, Sciences and Technologies - CONAHCYT, Mexico City, Mexico; Laboratory of Fibrosis and Cancer, Faculty of Medicine and Surgery, 'Benito Juárez' Autonomous University of Oaxaca - UABJO, Oaxaca, Mexico., Vásquez-Garzón VR; Deputy Directorate of Humanistic and Scientific Research, National Council of Humanities, Sciences and Technologies - CONAHCYT, Mexico City, Mexico; Laboratory of Fibrosis and Cancer, Faculty of Medicine and Surgery, 'Benito Juárez' Autonomous University of Oaxaca - UABJO, Oaxaca, Mexico., Muriel P; Laboratory of Experimental Hepatology, Department of Pharmacology, Center for Research and Advanced Studies of the National Polytechnic Institute - CINVESTAV-IPN, Mexico City, Mexico., Pérez-Carreón JI; Laboratory of Liver Diseases, National Institute of Genomic Medicine - INMEGEN, Mexico City, Mexico., Villa-Treviño S; Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute - CINVESTAV-IPN, Mexico City, Mexico., Arellanes-Robledo J; Laboratory of Liver Diseases, National Institute of Genomic Medicine - INMEGEN, Mexico City, Mexico; Deputy Directorate of Humanistic and Scientific Research, National Council of Humanities, Sciences and Technologies - CONAHCYT, Mexico City, Mexico. Electronic address: jarellanes@inmegen.gob.mx.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2024 Oct; Vol. 228, pp. 116209. Date of Electronic Publication: 2024 Apr 16.
DOI: 10.1016/j.bcp.2024.116209
Abstrakt: 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.X Ser139 . 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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