Diethylnitrosamine and 2-acetylaminofluorene chronic administration leads to biochemical and histologic changes related to hepatocellular carcinoma in Wistar rats

Abstract

Introduction and Objectives: This study aimed to analyze the biochemical and histological alterations produced in a model of chemical hepatocarcinogenesis by the chronic administration of diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in Wistar rats. Materials and methods: 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. The trial was approved by the research ethics committee. Results: 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. Discussion: Hepatocellular carcinoma models are a valuable tool to identify alterations during the progression of the disease. The Fischer-344 strain is frequently used in chemical hepatocarcinogenesis models since this strain shows greater susceptibility to the development of liver tumors. The damage induction model used in this work causes advanced hepatocellular carcinoma in Wistar rats, in spite of being a strain with intermediate susceptibility to hepatocarcinogenesis. The damage was evidenced by the presence of hepatomegaly, fibrosis, abundant nodules, histological changes, and biochemical alterations. Conclusion: Chronic administration of DEN and 2-AAF induces characteristic alterations of hepatocellular carcinoma in Wistar rats. Funding: The resources used in this study were from the hospital without any additional financing Declaration of interest: The authors declare no potential conflicts of interest.