Baicalein pre-treatment alleviates hepatic ischemia/reperfusion injury in mice by regulating the Nrf2/ARE pathway

Exp Ther Med. 2021 Dec;22(6):1380. doi: 10.3892/etm.2021.10816. Epub 2021 Sep 28.

Abstract

Hepatic ischemia-reperfusion injury (HIRI) is caused by blood flow recovery following ischemia. Baicalein (BAI), a natural antioxidant used in traditional Chinese medicine, eliminates excessive free radicals and protects the structure of the cell membrane. However, its protective mechanism against HIRI is still unclear. The present study investigated underlying mechanism using a mouse HIRI model. Liver injury was evaluated using serum levels of alanine aminotransferase and aspartate aminotransferase, and hematoxylin-eosin staining was performed to evaluate the pathological changes in liver tissue. Apoptosis of hepatocytes was detected by TUNEL staining. The expression levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver were detected to evaluate oxidative stress. Western blotting was performed to assess expression levels of nuclear factor E2-related factor 2 (Nrf2)/antioxidant response elements (ARE) pathway proteins in liver tissue. BAI pre-treatment significantly decreased elevation of serum aminotransferase levels induced by IR and alleviated histological damage to the liver. BAI decreased production of ROS and MDA in liver tissue induced by IR and increased the activity of SOD. At the same time, BAI inhibited apoptosis of liver cells induced by oxidative stress. Furthermore, BAI promoted the translocation of Nrf2 into the nucleus and increased the expression of total heme oxygenase-1 and NAD(P)H dehydrogenase quinone-1. The Nrf2 inhibitor ML385 reversed the protective effect of BAI on HIRI. These results indicated that BAI served a protective effect in HIRI by regulating the Nrf2/ARE pathway.

Keywords: baicalein; hepatic ischemia/reperfusion injury; nuclear factor E2-related factor 2 signaling; reactive oxygen species.

Grants and funding

Funding: The present study was supported by the National Natural Science Foundation of China (grant nos. 91949122 and 81771674), the 111 Project (grant no. D17011), the Guangxi Key Research and Development Plan (grant no. 2018AD03001) and the Self-Funded Scientific Research Project of Guangxi Zhuang Autonomous Region Health Commission (grant no. Z20200575).