Baicalein Protects Against Iron Overload Induced Liver Dysfunction in Thalassemic Mice

Abstract

Liver iron overload is a common and serious organ injury in β-thalassemia patients. Ferroptosis has been shown to play a crucial role in the pathological injury in iron overloaded hepatocytes. In our study, we focused on the protective effects of baicalein, a natural, active flavone extracted from an herb used in traditional Chinese medicine against RSL3-induced ferroptosis in hepatocytes and high iron diet (HID) induced liver iron-overload in a murine β654-thalassemia model. In vitro, the effects of baicalein on RSL3-induced hepatocyte ferroptosis were examined by testing ferroptosis related genes, protein, and the GSH, MDA, iron ion level by RT-PCR, Western blot and the commercial kits respectively. The anti-iron overload injury effects of baicalein were assessed in a β654-thalassemia mouse model of high iron diet induced liver injury by the same method In vitro experiments. Here, we found that baicalein could reverse cell ferroptosis in hepatocytes treated with RSL3. Importantly, changes in the iron ion content, and MDA and GSH levels in β654-thalassemia mouse livers were significantly restored by baicalein. Mechanistically, baicalein may activated the NRF2 antioxidant pathway and increased the expression of GPX4 in vivo and In vitro. We concluded that baicalein is a potential therapeutic drug for the treatment of iron overload in β-thalassemia.