Dimethylnitrosamine-Induced Liver Fibrosis and Recovery in NOD/SCID Mice

Abstract

There is a need for a new liver fibrosis model of immunodeficient mice to study the effects of cell therapy on liver disease because there are not many animal models available to study the effects of cell therapy. In this study, we induced liver fibrosis using dimethylnitrosamine (DMN) in NOD/SCID mice to create an animal model for liver disease. DMN (5 mg/kg, i.p.) was injected intraperitoneally for three consecutive days per week for 6 or 8 weeks, and the mice were sacrificed at weeks 0, 4 and 8 after the last DMN injection. The 6-week DMN-treated group gradually recovered from serum biochemical changes, histopathological toxic effects and lesions in the liver at weeks 4 and 8 after the last DMN injection. However, the progression of liver fibrosis and toxic levels were maintained in the 8-week DMN-treated group at week 4 after the last DMN injection. The increases in iron and extracellular matrix (collagen) in the DMN-treated group were confirmed by Prussian blue (PB) and Masson's trichrome (MT) staining, respectively. Additionally, activation of hepatic stellate cells was observed by alpha smooth muscle actin (α-SMA) immunostaining and western blot. In conclusion, treatment of NOD/SCID mice with 5 mg/kg of DMN for 8 weeks can be used to induce an appropriate animal model of disease for liver fibrosis. This model may be useful for evaluation of the efficacy and safety of cell therapies such as human mesenchymal stem cell therapy.