LipoxinA 4 analog BML-111 protects podocytes cultured in high-glucose medium against oxidative injury via activating Nrf2 pathway

• Published in: International immunopharmacology Vol. 111; p. 109170
• Main Authors: Hao, Hua, Xie, Fangping, Xu, Fen, Wang, Qingyu, Wu, Yun, Zhang, Dongxin
• Format: Journal Article
• Language: English
• Published: Netherlands 01.10.2022
• Subjects: Animals; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Glucose - metabolism; Heptanoic Acids; Mice; NF-E2-Related Factor 2 - metabolism; Oxidative Stress; Podocytes - metabolism; Nrf2; Podocytes; Inflammation; Lipoxin A; Diabetic kidney disease
• ISSN: 1878-1705

Numerous studies have shown that the activation of the Nrf2 pathway alleviates oxidative stress and podocyte damage. Emerging evidence indicates that the dual anti-inflammatory and pro-resolution lipid mediator, lipoxin A (LXA ), has antioxidant activity. The aim of the present study was to confirm that BML-111, an analog of LXA , prevents oxidative injury in diabetic podocytes via the regulation of the Nrf2 pathway. Here, we found that BML-111 inhibited high glucose (HG)-induced oxidative injury in the podocyte cell line, MPC5, in vitro, through activating Nrf2. Mechanistically, BML-111 significantly activated Nrf2 and its phase II enzymes, including Nqo1 and Ho-1. Moreover, BML-111 suppressed the migration of MPC5 cells. Additionally, BML-111 decreased the expression of Vcam, Icam and inflammatory cytokines (Il-1α, Il-6, and Tnf) in MPC5 cells. Importantly, BML-111 ameliorated blood glucose levels (approximately 75% of that in the SMZ group) and kidney damage by activating Nrf2, and its phase II enzymes, in diabetic mice. These effects are mainly mediated by Fpr2, a specific LXA receptor. Our findings demonstrate that BML-111 alleviates the injury of diabetic podocytes and kidneys by regulating the Nrf2 pathway.