Dapagliflozin inhibits ferroptosis to improve chronic heart failure by regulating Nrf2/HO-1/GPX4 signaling pathway

• DOI: 10.1371/journal.pone.0317295
• Publication Date: 2025-01-28T18:51:59Z
• Authors: Jing Zhang; Xuefeng Chen; Shilin Lv; Qingqing Hao
• Keywords: Malondialdehyde

Objective To study the effect of Dapagliflozin on ferroptosis in rabbits with chronic heart failure and to reveal its possible mechanism. Methods Nine healthy adult male New Zealand white were randomly divided into Sham group (only thorax opening was performed group, no ascending aorta circumferential ligation performed), Heart (HF HF establish animal model failure), (DAPA after rabbit successfully made DAPA group). given by force-feeding method. Echocardiography used assess cardiac function, HE staining evaluate pathological changes heart, Prussia blue observe iron ions myocardial tissue, enzyme-linked immunosorbent assay (ELISA) determine serum levels inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) at end week 12 and/or 16. The oxidative stress related indexes malondialdehyde (MDA), superoxide dismutase (SOD) (GSH-Px) quantitatively analyzed colorimetry. Protein expression nuclear factor E2-related 2(Nrf2), heme oxygenase-1(HO-1), glutathione peroxidase 4(Gpx4) detected Western blot. Results In animals failure, improved cardiomyocyte hypertrophy, degeneration necrosis. increased GSH-Px SOD decreased IL-1β, IL-6, TNF-α MDA (P < 0.05) a failure. also ion Nrf2, HO-1 GPX4 protein expression. Conclusion can improve inhibiting ferroptosis, mechanism may be regulation Nrf2/HO-1/GPX4 signaling pathway.