Suitable content of iron is essential for human body, but iron overload is associated with many kinds of diseases including chronic liver damage. Recently, researchers find that iron overload promotes hepatocyte autophagy and apoptosis. However, the mechanism of iron overload in liver damage remains unclear. In this study, Lo2 cells were selected as the research object, iron dextran was a model drug, and astragaloside IV was a therapeutic drug to explore the role of iron overload. MTT assay and Annexin/PI double staining were used to measure cell viability and apoptosis. Ultrastructure was observed by transmission electron microscopy. The expression levels of apoptosis and autophagy-related proteins were determined by real-time PCR and Western Blot. The results showed that iron dextran could significantly inhibit Lo2 cell viability and increase the apoptosis rate, while astragaloside IV could reverse the inhibition of Lo2 cell viability and decrease the apoptosis rate. Transmission electron microscopy showed a significant increase in the number of autophagosomes after administration of iron dextran, and the application of astragaloside IV reduced the production of autophagosomes. LC3II/I was significantly upregulated in the model group but decreased in the astragaloside IV treatment group, and P62 showed the opposite trend. Iron dextran significantly upregulated the expression of Bax and downregulated Bcl2, while astragaloside IV reversed this trend. Finally, the inhibition of hepcidin caused by iron dextran was counteracted by astragaloside IV. In conclusion, the experimental results show that the iron overload model mainly induces excessive autophagy and apoptosis of hepatocytes, thus causing damage to hepatocytes, but astragaloside IV plays a certain therapeutic role in reversing this damage.
[1]Nanjing Univ Tradit Chinese Med, Zhenjiang Affiliated Hosp, Dept Spleen Stomach, Zhenjiang, Jiangsu, Peoples R China.
[2]Zhenjiang Hosp Tradit Chinese Med, Dept Spleen Stomach, Zhenjiang, Jiangsu, Peoples R China.
[3]Peoples Hosp Yangzhong City, Dept Pharm, Zhenjiang, Jiangsu, Peoples R China.
[4]Dahua Hosp, Dept Pharm, Shanghai, Peoples R China.
[5]Shanghai Univ Tradit Chinese Med, Sch Basic Med Sci, Shanghai, Peoples R China.
[6]Nanjing Univ Chinese Med, Coll Pharm, Nanjing, Jiangsu, Peoples R China.
[7]Guanghua Hosp Integrated Tradit Chinese & Western, Dept Pharm, Shanghai, Peoples R China.
[8]Jiangsu Univ, Sch Pharm, Zhenjiang, Jiangsu, Peoples R China.
(8.0+极速模式)