EFFECT OF LIGUSTRAZINE ON A RAT MODEL WITH HEPATIC PRENEOPLASIA

Ligustrazine is a natural active alkaloid, widely distributed, with a variety of pharmacological activities. The aim of this study was to assess the effect of ligustrazine on rats with hepatic precancerous status, and to provide evidence for the clinical prevention and treatment of liver diseases, with ligustrazine. For the rat liver cancer model we used the diethyl nitrosamine (DEN) model. 24 male Wistar rats were randomly divided into the control group, DEN group and DEN + ligustrazine group. The rats in DEN group were treated with DEN (55 mg/kg b.w.) i.p. twice a week. The rats in DEN + ligustrazine group were treated with DEN (55 mg/kg b.w.) i.p. twice a week and ligustrazine solution (163 mg/kg b.w.) daily. The rats in the control group were treated i.p. with the same volume of normal saline. After 15 weeks the rats from the three groups were sacrificed and the blood and liver collected for analysis. The liver tissue structure and cell morphology of the three groups of rats were assessed by light microscopy. The expression of alpha-fetoprotein (AFP) in the three groups was verified using immunohistochemistry (IHC). In the DEN group the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutathione S-transferase (GST), total bilirubin (TB), and malondialdehyde (MDA) was significantly increased than in the control group (p < 0.01). Compared with DEN group, the levels of AST, ALT, GST and TB in serum in DEN + ligustrazine group was significantly decreased (p < 0.05), while MDA in serum was more significantly decreased (p < 0.01). The hepatic tissue structure and cell morphology of the rats in the control group were normal. The liver of the rats in DEN model group had hepatic precancerous lesions and the liver cells were characterized by nodular hyperplasia and enhanced shape of typical cancer cells. The bile ducts epithelium was characterized by hyperplasia and significant atypia. The liver of rats in the DEN + ligustrazine group showed the common features of the first three lesions, but did not presented clear cancer cells.