• Modeling Mechanism：

  Dimethylnitrosamine (DMN), a liver-specific chemical carcinogen, is activated by hepatic cytochrome P450 enzymes after entering the body, producing alkylating intermediates that cause DNA damage in hepatocytes (such as increased production of 8-hydroxydeoxyguanosine). Simultaneously, it triggers oxidative stress (accumulation of reactive oxygen species (ROS) and decreased antioxidant enzyme activity), inhibits the Nrf2/ARE antioxidant pathway, activates hepatic stellate cells and transforming growth factor β (TGF-β) signaling, and promotes collagen deposition and liver fibrosis.

• Related Products：

  Dimethylnitrosamine (T82552)

• Modeling Method：

  Experimental Subject：

  Mice, Balb/c, male, 5 weeks old, body weight 18–22 g

  Dosage and Administration Route：

  ① Core modelling (fibrosis - precancerous stage):
  - DMN, 10 mg/kg, dissolved in 0.9% saline, intraperitoneal injection;
  ② Complete Liver Tumour Modelling (Long-Term Extension):
  - Following initial modelling, continue conventional housing or maintain low-dose DMN (5 mg/kg, weekly) for 16–24 weeks (to induce hepatocellular carcinoma formation);
  ③ Control treatment: Control group administered equal-volume saline solution via intraperitoneal injection, with all other housing conditions identical;
  ④ Intervention validation group (optional):
  - Antioxidant intervention: Nrf2 activators (e.g., sulforaphane) and glutathione (GSH) supplements administered concurrently with modelling

  Dosing Frequency and Duration Model：

  Twice weekly for 4 consecutive weeks

• Validation：

  1. Pathological Indicators: - Liver fibrosis: Masson's trichrome staining showed a significant increase in collagen deposition in liver tissue, enhanced positive signal of α-smooth muscle actin (α-SMA) immunostaining, destruction of liver lobule structure, and sinusoidal congestion; - Hepatocellular injury: HE staining showed extensive hepatocellular necrosis and inflammatory infiltration, and abnormal proliferative nodules of hepatocellular cells were observed in long-term modeling; 2. Biochemical Indicators: - Serum transaminases: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly elevated (p<0.01), indicating hepatocellular injury; - Oxidative stress: Total antioxidant capacity (TAC) of liver tissue decreased, GSH level and GSH/GSSG ratio decreased, and SOD and catalase activities decreased (p<0.05); - Oxidative damage markers: 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE) expression was upregulated in liver tissue; 3. Functional and Molecular Indicators: - Liver function: Indocyanine green (ICG) clearance test showed decreased liver metabolic function; - Redox status: DNP-MRI showed a significantly slowed reduction rate of carbamoyl-PROXYL in liver tissue (0.11±0.02 min⁻¹ vs. control group 0.18±0.02 min⁻¹, p<0.01); - Signaling pathways: TGF-β and α-SMA mRNA and protein expression were upregulated in liver tissue, while Nrf2 expression was downregulated.

*Precautions：

*References：Kawano T,et,al. Noninvasive mapping of the redox status of dimethylnitrosamine-induced hepatic fibrosis using in vivo dynamic nuclear polarization-magnetic resonance imaging. Sci Rep. 2016 Sep 2;6:32604.