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Updated: May 16, 2026
The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat
Published on: June 17, 2016
Histology, bioenergetics and oxidative stress in mouse liver exposed to N-diethylnitrosamine
Nuno Paula Santos1, Ivo Conceição Pereira, Maria João Pires
1Veterinary and Animal Science Research Centre, Department of Veterinary Science, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.
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.
