Journal of Gastroenterology & Digestive Systems(JGDS)
ISSN: 2640-7477 | DOI: 10.33140/JGDS
Impact Factor: 1.13*
Fast Induction of Hcc in Nash Rodent Model: A Simple Diet Associated with A Chemical Carcinogen
Abstract
Carolina Antunes Marques, Ana Beatriz Souza de Oliveira, Cinthia Laureano Pavan, Claudia P Oliveira, Ilka de Fatima Santana Ferreira Boin, Bruno Cogliati, Dalisio Santi Neto, Rita de Cassia Martins Alves da Silva, Renato Ferreira da Silva
Introduction: Non-alcoholic fatty liver disease (NAFLD) have been increasing as an important cause of hepatocellular carcinoma (HCC). Experimental models are crucial to identify some pathways in the pathogenesis of HCC secondary to NAFLD.
Objective: To systematize an experimental hybrid rodent model of HCC secondary to NAFLD.
Material and Methods: Fourteen male Sprague-Dawley rats, weighting 350-500g, were fed with choline-deficient high-fat diet and diethylnitrosamine (DEN) in the drinking water for 16 weeks. The animals were separated into two groups: 7 received DEN in water (100mg/ml) associated to choline-deficient high-fat diet and 7 received only cholinedeficient high-fat diet. Histological and immunohistochemical analysis were also performed.
Results: All animals had definitive diagnosis of NASH in both groups with hepatocellular ballooning, steatosis and inflammation. In the group that received high-fat choline deficient diet, only two animals had micro nodular cirrhosis. However, in DEN group with high-fat choline deficient diet, all animals had gross lesions, major nodulations and fibrosis, visible in macroscopy. Besides, according of Edmondson-Steiner classification, 71% of the animals that received DEN + Diet with positive CK19 and oval cells and developed some grades of dysplastic and tumoral lesions. Moreover, in this model we could identify beyond NASH progression, some tumor-development stages, which means this model shows different treatment and study targets.
Conclusion: The model is accomplishable, promotes fast induction of HCC in NAFLD context without much complexity to be executed and will be implemented as an interesting model to study new drugs to HCC secondary a NASH.