Artemisitene Alters LPS-Induced Oxidative stress, inflammation and Ferroptosis in Liver Through Nrf2/HO-1 and NF-kB Pathway

Changzhi Zhao; Congshu Xiao; Songqiao Feng; Jianxin Bai

doi:10.3389/fphar.2023.1177542

Artemisitene Alters LPS-Induced Oxidative stress, inflammation and Ferroptosis in Liver Through Nrf2/HO-1 and NF-kB Pathway

Front Pharmacol. 2023 Apr 25:14:1177542. doi: 10.3389/fphar.2023.1177542. eCollection 2023.

Authors

Changzhi Zhao^{1

2}, Congshu Xiao¹, Songqiao Feng¹, Jianxin Bai¹

Affiliations

¹ Second Affiliated Hospital of Dalian Medical University, Dalian, China.
² Dalian Municipal Friendship Hospital, Dalian, China.

Abstract

The liver plays a critical role in sepsis, which is a serious worldwide public health problem. A novel mechanism of controlled cell death called ferroptosis has recently been described. Disrupted redox equilibrium, excessive iron, and enhanced lipid peroxidation are key features of ferroptosis. It is unknown how ferroptosis affects liver damage caused by sepsis. In the present study, we aimed to elucidate the pathways and explore the impact of artemisitene (ATT) on ferroptosis in sepsis-induced liver injury. Our findings demonstrated that ATT significantly decreased liver damage and ferroptotic characteristics. Additionally, ATT significantly reduced the expression of the nuclear factor-κB (NF-κB) subunit to reduce LPS-induced hepatic oxidative stress and inflammation and upregulated the expression of nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) and its downstream protein heme oxygenase 1 (HO-1). This may offer a new strategy for preventing LPS-induced hepatic injury.

Keywords: NF-κB; Nrf2; artemisitene; ferroptosis; liver sepsis.