Related Experiment Video
Updated: Apr 26, 2026
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Chemotherapy-associated steatohepatitis induced by irinotecan: a novel animal model
Marcelo Leite Vieira Costa1, Roberto César Pereira Lima-Júnior, Karoline Sabóia Aragão
1Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará (UFC), Rua Cel. Nunes de Melo, 1127-Rodolfo Teófilo, 60430-270, Fortaleza, Ceará, Caixa-Postal: 3157, Brazil, marcelolvcosta@gmail.com.
Purpose:
Nonalcoholic steatohepatitis (NASH) has been associated with irinotecan (IRI)-based cancer chemotherapy regimens. The purpose of this study was to propose and test a consistent model of IRI-induced NASH, filling a gap in the medical literature.
Methods:
Swiss male mice were distributed in groups (n = 8) and injected with saline (5 mL/kg, i.p.; control) or IRI (25, 50, 75 or 100 mg/kg, i.p.) thrice a week for 7 weeks. Blood samples were collected to measure the serum concentrations of proteins, alanine and aspartate aminotransferases (ALT and AST). Each week animals were euthanized, and the livers were submitted to myeloperoxidase (MPO) assay, lipid dosage, immunohistochemistry for inducible nitric oxide synthase (iNOS), TNF-α and interleukin-1β (IL-1β), and histopathological analysis. Survival rates were also determined.
Results:
Mice treated with IRI had a significantly (p < 0.05) lower survival rate than controls and time- and dose-dependent body weight loss. ALT and AST plasma levels increased in relation to controls only in mice receiving IRI 50 mg/kg (p < 0.05). The histopathological features characteristic of NASH was observed, including steatosis, lobular neutrophil infiltration and ballooning hepatocytic degeneration. Additional findings included increased MPO, lipid accumulation, portal neutrophil infiltration, IL-1β and iNOS expression and fibrosis in liver tissues and low serum protein levels compared to controls.
Conclusion:
This is the first report of a consistent model of IRI-induced NASH capable of mimicking clinical findings.
