Abstract: Objective To study the lipid peroxidation of human normal hepatocyte L02 induced by pyrazinamide (PZA) and to explore the related mechanism of liver injury. Methods L02 cells were treated with different concentrations of PZA solution and N-acetyl-L-cysteine (NAC). The effects of PZA and NAC on L02 cells were detected by MTT, while the level of reactive oxygen species (ROS), the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in L02 cells were detected. Results MTT results showed that the 50% inhibitory concentration (IC₅₀) of L02 cells treated with PZA for 24, 48 and 72 h was 1 753.36, 1 344.32 and 1 367.80 µg·mL^-1, respectively, and the inhibition rate was concentration- dependent, but the inhibition rate of 3 125 µg·mL^-1 PZA was time-dependent. Compared with the control group, the intracellular ROS content of the 125, 625 µg·mL^-1 PZA group was significantly higher than that of the control group. The intracellular MDA content increased significantly in 625 and 3 125 µg·mL^-1 PZA groups, but the intracellular SOD activity decreased significantly in 125,3 125 µg· µg·mL^-1 PZA groups. Compared with PZA alone, the ROS content decreased in 10 mmol·L^-1 NAC+125 and 625 µg· µg·mL^-1 PZA groups, MDA content decreased significantly in 10 mmol·L^-1 NAC+625 and 3 125 µg·mL^-1 PZA groups, and SOD activity increased in 10 mmol·L^-1 NAC+625 and 3 125 µg·mL^-1 PZA groups. Conclusion PZA can reduce the ability of the antioxidant system of L02 cells, induce lipid peroxidation in L02 cells, lead to apoptosis of L02 cells and damage hepatocytes. The combined use of NAC can reduce the severity of liver injury to some extent.

Key words: pyrazinamide, L02 cells, MTT method, lipid peroxidation, liver injury