Maresin1 Protect Against Ferroptosis-Induced Liver Injury Through ROS Inhibition and Nrf2/HO-1/GPX4 Activation

• DOI: 10.3389/fphar.2022.865689
• Publication Date: 2022-04-04T07:08:09Z
• Authors: Wenchang Yang; Yaxin Wang; Chenggang Zhang; Yongzhou Huang; Jiaxian Yu; Liang Shi; Peng Zhang; Yuping Yin; Ruidong Li; Kaixiong Tao
• Keywords: Aspartate transaminase; Malondialdehyde; Viability assay

Drugs, viruses, and chemical poisons stimulating live in a short period of time can cause acute liver injury (ALI). ALI further develop into serious diseases such as cirrhosis cancer. Therefore, how to effectively prevent treat has become the focus research. Numerous studies have reported Maresin1 (MaR1) anti-inflammatory effect protective functions on organs. In present study, we used d-galactosamine/lipopolysaccharide (D-GalN/LPS) establish an model, explored mechanism cells death caused by D-GalN/LPS, determined MaR1 D-GalN/LPS-induced ALI. vivo experiments, found that ferrostatin-1 significantly alleviated ALI, reduced serum alanine transaminase aspartate levels, improved survival rate mice. Meanwhile, inhibited hepatocyte death, tissue reactive oxygen species (ROS) expression, malondialdehyde (MDA), glutathione (GSH), GSH/oxidized (GSSG), iron content induced D-GalN/LPS addition, ferroptosis-induced through inhibiting release interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6. Subsequently, western blot showed expression nuclear factor E2-related 2(Nrf2)/heme oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4). vitro LPS-induced erastin-induced cell viability reduction. increased MDA GSH levels cells. Western level Nrf2/HO-1/GPX4. Next, Nrf2 was knocked down HepG2 cells, results decreased. Finally, flow cytometry revealed ROS production apoptosis. Overall, our study Nrf2/HO-1/GPX4 activation.