Avaliação do efeito da rifaximina na carcinogênese hepática experimental secundária à doença hepática gordurosa não alcoólica

Introdução: A doença hepática gordurosa não alcoólica, atualmente, é considerada a forma mais comum de hepatopatia crônica, tendo como complicação mais grave o carcinoma hepatocelular Considerando que a rifaximina é um antibiótico efetivo como tratamento de diversas doenças gastrointestinais e hepáticas, este estudo tem como objetivo avaliar os efeitos da rifaximina em um modelo de carcinoma hepatocelular secundário à doença hepática gordurosa não alcoólica. Métodos: Ratos Sprague-Dawley adultos foram divididos em 3 grupos. 1) grupo CHC: os animais foram alimentados com dieta hiperlipídica deficiente em colina e expostos a dietilnitrosamina (135mg/L) na água de beber; 2) grupo RIF+CHC: os animais receberam a mesma dieta e dietilnitrosamina, no entanto, na 5ª semana receberam 50mg/kg/dia de rifaximina por gavagem; 3) grupo Controle: os animais foram alimentados com dieta e água padrão. Após 16 semanas, os animais foram eutanasiados. Parâmetros bioquímicos séricos de Colesterol Total, HDL, LDL, Triglicerídeos, AST, ALT e Fosfatase Alcalina foram avaliados. O tecido hepático foi avaliado macroscopicamente e amostras foram coradas com Hematoxilina & Eosina e Picrosirius Red. As variáveis histológicas foram pontuadas usando o sistema modificado de Kleiner, NAFLD activity score e grau de fibrose. O carcinoma hepatocelular foi classificado de acordo com a graduação de Edmondson-Steiner. Resultados: Os níveis séricos de colesterol total, LDL, AST e fosfatase alcalina foram menores no grupo CHC+RIF quando comparados ao grupo CHC, no entanto a diferença não foi estatisticamente significativa. O escore de NAFLD activity score ficou alocado entre 3 e 5 para o grupo CHC, no entanto, para o grupo CHC+RIF permaneceu em grau 3. O grau de câncer foi de 3 e 4 para os grupos CHC+RIF e 7 CHC, mas curiosamente em 3 animais tratados com Rifaximina não apresentaram câncer. Conclusão: Estes resultados preliminares mostram que o tratamento com rifaximina parece ter um efeito moderadamente benéfico sobre o desenvolvimento da esteato-hepatite não alcoólica e do carcinoma hepatocelular.Introduction: Non-alcoholic fatty liver disease is currently considered the most common form of chronic liver disease, with hepatocellular carcinoma being the most serious complication. Considering that rifaximin is a highly effective nonabsorbable antibiotic for the treatment of various gastrointestinal and hepatic diseases, this study aims to evaluate the effects of rifaximin in a model of hepatocellular carcinoma secondary to nonalcoholic fatty liver disease. Methods: Adult Sprague-Dawley rats were divided into 3 groups. 1) HCC group: animals were fed a choline-deficient hyperlipid diet and exposed to diethylnitrosamine (135mg/L) in drinking water; 2) RIF+HCC group: animals received the same diet and diethylnitrosamine; however, at week 5, they received 50mg/kg/day of rifaximin by gavage; 3) Control group: the animals were fed standard diet and water. After 16 weeks, the animals were euthanized. Serum biochemical parameters of Total Cholesterol, HDL, LDL, Triglycerides, AST, ALT and Alkaline Phosphatase were evaluated. The liver tissue was macroscopically evaluated, and the samples were stained with Hematoxylin & Eosin and Picrosirius Red. Histological variables were scored using Kleiner’s modified system, NAFLD activity score, and degree of fibrosis. Hepatocellular carcinoma was classified according to Edmondson-Steiner. Results: The serum levels of total cholesterol, LDL, AST and alkaline phosphatase were lower in the CHC+RIF group when compared to the HCC group. The difference, however, was not statistically significant. The NAFLD activity score was allocated between 3 and 5 for the HCC group; however, for the CHC+RIF group, it remained in 9 grade 3. The degree of cancer was 3 and 4 for the CHC+RIF and HCC groups, but curiously, 3 animals treated with rifaximin did not present cancer. Conclusion: These preliminary results show that treatment with rifaximin appears to have a moderately beneficial effect on the development of nonalcoholic steatohepatitis and hepatocellular carcinoma

Experimental model of hepatic steatosis by fructose in adult zebrafish : a pilot study

The consumption of fructose has been questioned, since its increase has led to an associated increase in steatosis caused by nonalcoholic fatty liver disease. Despite the advantages presented by the zebrafish as an animal model, at present there are no models of steatosis by fructose in adult zebrafish. The aim of this study is to establish a model of hepatic steatosis by fructose in adult zebrafish. Methods: Firstly, adult zebrafish were daily exposed to 4% or 6% fructose. Then, animals were exposed to 6% fructose every 2 days. The hepatic lipid accumulation was analyzed by Nile Red and Oil Red O staining. Results: The daily exposure to 6% fructose showed increased accumulation of hepatic lipids when compared to 4% and control groups, but the same concentration showed no difference when the exposure happened every 2 days. Conclusion: We can suggest the daily exposure to a concentration of 6% fructose can be considered as a new experimental model of adult zebrafish

Experimental model of hepatic steatosis by fructose in adult zebrafish: a pilot study

Introduction: The consumption of fructose has been questioned, since its increase has led to an associated increase in steatosis caused by nonalcoholic fatty liver disease. Despite the advantages presented by the zebrafish as an animal model, at present there are no models of steatosis by fructose in adult zebrafish. The aim of this study is to establish a model of hepatic steatosis by fructose in adult zebrafish. Methods: Firstly, adult zebrafish were daily exposed to 4% or 6% fructose. Then, animals were exposed to 6% fructose every 2 days. The hepatic lipid accumulation was analyzed by Nile Red and Oil Red O staining. Results: The daily exposure to 6% fructose showed increased accumulation of hepatic lipids when compared to 4% and control groups, but the same concentration showed no difference when the exposure happened every 2 days. Conclusion: We can suggest the daily exposure to a concentration of 6% fructose can be considered as a new experimental model of adult zebrafish. Keywords: Fatty liver; fructose; zebrafis

Environmental risk factors associated with biliary atresia in Rio Grande do sul, Brazil

Biliary atresia (BA) seems to be a multifactorial disorder in which environmental factors interact with the patient’s genetic constitution. This study aimed to analyze information concerning environmental risk factors associated with BA in southern Brazil. A case-control study with mothers of patients with BA and mothers of patients with cystic fibrosis (CF) was conducted. Inquiry included questions related to exposition to environmental risk factors during the periconceptional and gestational (second and third trimesters) periods. Mothers of BA patients had smoked during pregnancy more frequently in comparison with the mothers of CF patients, but no significant difference was found in a multivariate analysis. There was no between group difference in terms of seasonality, but the multivariate analysis showed a significant difference within the BA group between date of conception in winter compared to other seasons. In conclusion, smoking during pregnancy seemed to increase the risk of BA while date of conception in winter decreased it.info:eu-repo/semantics/publishedVersio

Environmental risk factors associated with biliary atresia in Rio Grande do Sul, Brazil

Biliary atresia (BA) seems to be a multifactorial disorder in which environmental factors interact with the patient’s genetic constitution. This study aimed to analyze information concerning environmental risk factors associated with BA in southern Brazil. A case-control study with mothers of patients with BA and mothers of patients with cystic fibrosis (CF) was conducted. Inquiry included questions related to exposition to environmental risk factors during the periconceptional and gestational (second and third trimesters) periods. Mothers of BA patients had smoked during pregnancy more frequently in comparison with the mothers of CF patients, but no significant difference was found in a multivariate analysis. There was no between group difference in terms of seasonality, but the multivariate analysis showed a significant difference within the BA group between date of conception in winter compared to other seasons. In conclusion, smoking during pregnancy seemed to increase the risk of BA while date of conception in winter decreased it.Keywords: Biliary atresia; environmental risk factor; etiology; seasonality; smokin