P- 78 DIETHYlNITROSAMINE AND 2-ACETYLAMINOFLUORENE CHRONIC ADMINISTRATION LEADS TO BIOCHEMICAL, HISTOLOGIC AND GENETIC CHANGES RELATED TO HEPATOCELLULAR CARCINOMA IN WISTAR RATS

• Published in: Annals of hepatology 2023-03, Vol.28, p.100973, Article 100973
• Main Authors: Sánchez-Meza, Jaime, Campos-Valdez, Marina, Domínguez-Rosales, José Alfredo, Rodríguez-Reyes, Saraí Citlalic, Martínez-López, Erika, Godínez-Rubí, Juliana Marisol, Salazar-Montes, Adriana María, Sánchez-Orozco, Laura Verónica
• Format: Article
• Language: English
• ISSN: 1665-2681; 2659-5982
• DOI: 10.1016/j.aohep.2023.100973

Hepatocellular carcinoma (HCC) is one of the neoplasms with the highest mortality worldwide. The causes of the development of HCC have been related to hepatitis B virus and exposure to aflatoxin B1; however, chronic alcohol use, nonalcoholic fatty liver disease, and hepatitis C virus infection are the most important risk factors for developing HCC. The establishment of animal models of HCC is crucial for both basic and translational studies of hepatocellular carcinoma and is a valuable tool to identify alterations during the progression of the disease. This study aimed to analyze the biochemical, histological, and gene expression alterations produced in a model of chemical hepatocarcinogenesis by the chronic administration of diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in Wistar rats. Twelve Wistar rats weighing 180 to 200 g were divided into control and damage groups: rats were treated with DEN (50 mg/kg/wk) i.p and an intragastric dose of 2-AAF (25 mg/kg/wk) for 18 weeks. Serum clinical biochemistry was performed on VITROS Chemistry System 350® equipment. Masson's trichrome and Hematoxylin-Eosin stains were performed on the liver tissue. Relative gene expression was performed by RT-qPCR in LightCycler®96. The damage group had significant increases in total cholesterol, HDL-C, AST, ALT, ALKP, and GGT. Furthermore, histological analysis showed the loss of normal liver architecture with nuclear pleomorphism in the hepatocytes, atypical mitosis, and fibrous septa distributed between portal triads and collagen fibers through the hepatic sinusoids. The expression of TGFb1 was significantly increased (p