Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

作     者：Matheus Truccolo Michalczuk Larisse Longo Melina Belén Keingeski Bruno de Souza Basso Gabriel Tayguara Silveira Guerreiro Jessica T Ferrari JoséEduardo Vargas Cláudia P Oliveira Carolina Uribe-Cruz Carlos Thadeu Schmidt Cerski Eduardo Filippi-Chiela Mário ReisÁlvares-da-Silva 

作者机构：Division of GastroenterologyHospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Graduate Program in Gastroenterology and HepatologyUniversidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Experimental Laboratory of Hepatology and GastroenterologyHospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Laboratory of Inflammatory and Neoplastic CellsUniversidade Federal do ParanáParaná81530900Brazil Department of Gastroenterology(LIM07)Faculdade de Medicina da Universidade de São PauloSão Paulo 01246903Brazil Facultad de Ciencias de la SaludUniversidad Católica de las MisionesPosadasMisiones 3300Argentina Unit of Surgical PathologyHospital de Clinicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Center of BiotechnologyUniversidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Department of Morphological SciencesUniversidade Federal do Rio Grande do SulPorto Alegre 90.050-170Rio Grande do SulBrazil Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)ResearcherBrasília 71.605-001Brazil 

出 版 物：《World Journal of Hepatology》 (世界肝病学杂志（英文版）（电子版）)

年 卷 期：2024年第16卷第1期

页      面：75-90页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Supported by the following Brazilian funding agencies:Financiamento e IncentivoàPesquisa from Hospital de Clínicas de Porto Alegre(FIPE/HCPA),No.2021-0105(toÁlvares-da-Silva MR) Coordination for the Improvement of Higher Education Personnel,CAPES/PNPD and this study was financed in part by the Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)(toÁlvares-da-Silva MR) 

主　　题：Animal model Autophagy Epigenetic Hepatocellular carcinoma Metabolic dysfunction-associated steatotic liver disease Rifaximin 

摘      要：BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in *** Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were *** All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop *** animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the *** opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-*** with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis throu