Animal models as a tool in hepatocellular carcinoma research: A Review.

Cancer is the first cause of death in developed countries and the second in developing countries. Concerning the most frequent worldwide-diagnosed cancer, primary liver cancer represents approximately 4% of all new cancer cases diagnosed globally. However, among primary liver cancer, hepatocellular carcinoma is by far the most common histological subtype. Notwithstanding the health promotion and disease prevention campaigns, more than half a million new hepatocellular carcinoma cases are reported yearly, being estimated to growth continuously until 2020. Taking this scenario under consideration and the fact that some aspects concerning hepatocellular carcinoma evolution and metastasize process are still unknown, animal models assume a crucial role to understand this disease. The animal models have also provided the opportunity to screen new therapeutic strategies. The present review was supported on research and review papers aiming the complexity and often neglected chemically induced animal models in hepatocarcinogenesis research. Despite the ongoing debate, chemically induced animal models, namely, mice and rat, can provide unique valuable information on the biotransformation mechanisms against xenobiotics and apprehend the deleterious effects on DNA and cell proteins leading to carcinogenic development. In addition, taking under consideration that no model achieves all hepatocellular carcinoma research purposes, criteria to define the " ideal" animal model, depending on the researchers' approach, are also discussed in this review.

Histology, bioenergetics and oxidative stress in mouse liver exposed to N-diethylnitrosamine.

BACKGROUND: A mouse model in which N-diethylnitrosamine (DEN) induces Hepatocellular carcinoma (HCC) has histological and genetic resemblance to human tumours. MATERIAL AND METHODS: Male ICR mice were divided into control (n=10) and DEN-treated (n=10) groups. DEN was administered via intraperitoneal injection, once a week, for eight consecutive weeks. Animals were euthanized seven weeks after the last administration of DEN and their livers were collected. Plasma albumin, total bilirubin, alanine transaminase and aspartate aminotransferase activity were all measured and liver mitochondrial bioenergetics and oxidative stress were also evaluated. RESULTS: Histologically, pre-neoplastic lesions were identified in the livers of mice from the DEN group. Total plasma bilirubin increased significantly in the group exposed to DEN and mitochondrial complex I and IV were significantly inhibited (p=0.0403 and p=0.0053, respectively). CONCLUSION: DEN induced changes in liver bioenergetics and antioxidant capacity towards reactive oxygen species, seven weeks after administration. At this stage, liver tissues in mice exposed to DEN still had the ability to counteract the oxidative effects of DEN by increasing the activity of antioxidant enzymes.