Ruscogenin Prevents Folic Acid-Induced Acute Kidney Damage by Inhibiting Rev-erbα/β-Mediated Ferroptosis

Abstract

To investigate the pharmacodynamic effects of ruscogenin on acute kidney injury and the Rev-erbα/β regulation of ferroptosis intervention mechanism. The C57BL-6 mice were induced acute kidney injury with folic acid. Plasma, urine, and kidney samples were collected after intraperitoneal injection of ruscogenin (0.01, 0.1, and 1 mg/kg). We measured mouse kidney function indicators, including creatinine (CRE), blood urea nitrogen (BUN), N-acetyl-β-D-glucosidase (NAG), albumin, albumin and creatinine rate (ACR), renal index, and renal injury molecule-1 expression. Meanwhile, we detected the levels of ferroptosis indicators malondialdehyde (MDA), carbonylated proteins, iron ions, glutathione peroxidase 4 (GPX-4), and glutathione (GSH). The expression of solute carrier family 7 member 11 (Slc7a11), heme oxygenase-1 (HO-1), and Rev-erbα/β were detected by the Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. Ruscogenin (1 mg/kg) significantly reduced the index of folic acid-induced acute kidney injury and alleviated acute kidney injury. In kidney tissues, ruscogenin inhibited folic acid-induced Rev-erbα/β expression, restored HO-1 and SLC7A11 expression to normal levels, and alleviated ferroptosis. Ruscogenin ameliorates acute kidney injury via suppressing ferroptosis in kidney tissues through modulation of the Rev-erbα/β-SLC7A11/HO-1 pathway.