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 

机构地区：[1]Division of Gastroenterology,Hospital de Clínicas de Porto Alegre,Porto Alegre 90035-903,Rio Grande do Sul,Brazil [2]Graduate Program in Gastroenterology and Hepatology,Universidade Federal do Rio Grande do Sul,Porto Alegre 90035-003,Rio Grande do Sul,Brazil [3]Experimental Laboratory of Hepatology and Gastroenterology,Hospital de Clínicas de Porto Alegre,Porto Alegre 90035-903,Rio Grande do Sul,Brazil [4]Laboratory of Inflammatory and Neoplastic Cells,Universidade Federal do Paraná,Paraná81530900,Brazil [5]Department of Gastroenterology(LIM07),Faculdade de Medicina da Universidade de São Paulo,São Paulo 01246903,Brazil [6]Facultad de Ciencias de la Salud,Universidad Católica de las Misiones,Posadas,Misiones 3300,Argentina [7]Unit of Surgical Pathology,Hospital de Clinicas de Porto Alegre,Porto Alegre 90035-903,Rio Grande do Sul,Brazil [8]Center of Biotechnology,Universidade Federal do Rio Grande do Sul,Porto Alegre 90035-003,Rio Grande do Sul,Brazil [9]Department of Morphological Sciences,Universidade Federal do Rio Grande do Sul,Porto Alegre 90.050-170,Rio Grande do Sul,Brazil [10]Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq),Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)Researcher,Brasília 71.605-001,Brazil

出　　处：《World Journal of Hepatology》2024年第1期75-90,共16页世界肝病学杂志（英文版）（电子版）

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).

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 animals.METHODS 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 obtained.RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop HCC.Comparing 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 HCC-group.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)-protein.Comparing with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P<0.05).Carm1 was lower in HCC compared to RIF(P<0.05).Hepatic expression of Mmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(P<0.05).Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and Mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P<0.05).miR-26b was lower in HCC compared to RIF,and the inverse was observed for miR-224(P<0.05).There was no difference among groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD

关 键 词：Animal model AUTOPHAGY Epigenetic Hepatocellular carcinoma Metabolic dysfunction-associated steatotic liver disease RIFAXIMIN 

分 类 号：R735.7[医药卫生—肿瘤]