Establishment of a Stable Acute Drug-Induced Liver Injury Mouse Model by Sodium Cyclamate

Abstract

Quan Zhou,1,2 Zhongtian Peng,2 Xialing Huang2,3 1Department of Infectious Diseases, The First Hospital of Changsha, Changsha, Hunan, 410000, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 3Department of Infectious Diseases, Leiyang People’s Hospital, Leiyang, Hunan, 421800, People’s Republic of ChinaCorrespondence: Zhongtian Peng, Department of Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China, Tel [phone], Email [email protected] Xialing Huang, Department of Infectious Diseases, Leiyang People’s Hospital, Leiyang, Hunan, 421800, People’s Republic of China, Tel [phone], Email [email protected]: To establish a stable acute DILI mouse model and explore its possible pathogenesis.Methods: Mice were randomly divided into control, low-dose, middle-dose and high-dose sodium cyclamate groups. Mice in the model group were intraperitoneally injected with corresponding doses of sodium cyclamate, and in the control group intraperitoneally injected with 0.9% normal saline. The toxic effects of sodium cyclamate on liver, heart, kidney were evaluated by biochemical index level and histomorphologically observed. The expression of TNF-α and IL-1β were measured by immunohistochemistry.Results: 1. The level of ALT in the low-dose and middle-dose groups at 24h, 72h, 120h and 168h were increased, also in the high-dose group at 24h, 72h and 120h. The level of AST in the low-dose group at 72h, 120h, 168h and in the middle-dose group at 168h were increased, also in the middle-dose and high-dose groups at 24h, 72h and 120h. The levels of CK, CK-MB and cTnT in the low-dose and middle-dose groups at 168h were increased, also in the high-dose group at 24h, 72h and 120h. 2. The damage of hepatocytes increased with the increase of sodium cyclamate dosage and treated time. 3. At 120h, the IOD/Area of TNF-α and IL-1β positive expression increased in the liver tissues with the increase of the dosage. In the heart and kidney tissues, the IOD/Area of TNF-α and IL-1β positive expression in the high-dose group increased significantly. In the kidney tissues, the IOD/Area of IL-1β positive expression in the middle-dose group increased significantly.Conclusion: Sodium cyclamate-induced acute DILI mouse model can be established by intraperitoneal injection of 6000 mg/kg/day sodium cyclamate for 5 days successfully. The toxicity of sodium cyclamate to liver showed a dose-response and time-response relationship. Sodium cyclamate induced liver, heart and kidney injury closely related to the inflammatory response mediated by TNF-α and IL-1β.Keywords: sodium cyclamate, acute liver injury, animal model, TNF-α, IL-1β

Keywords

• sodium cyclamate
• acute liver injury
• animal model
• tnf-α
• il-1β