Biochanin A ameliorates vancomycin-induced acute kidney injury via modulation of the JAK2/STAT-3/GPX4 axis.

Vancomycin (VAN) is a commonly used antibiotic for the treatment of severe Gram-positive bacterial infections. However, its major dose-limiting adverse effect remains nephrotoxicity. Biochanin A (BCA) is a natural isoflavone that has been reported to have antioxidant and anti-inflammatory actions. In this work, we evaluated the nephroprotective efficacy of BCA against VAN-induced acute kidney injury (VAN-AKI). Thirty-six male Swiss mice were allocated into six experimental groups (n = 6/group): control, vehicle, BCA (40 mg/kg), VAN (400 mg/kg), VAN + BCA (20 mg/kg), and VAN + BCA (40 mg/kg). Biochanin A (20 or 40 mg/kg, i.p.) was given 30 min before VAN (400 mg/kg, i.p.). Except for the control group, all treatments were given once a day for 7 consecutive days. Biomarkers of renal function, indices of oxidative stress, inflammatory cytokines, histological changes, and immunohistochemistry expression of JAK2, STAT3, GPX4, and caspase-3 were investigated. Administration of VAN induced substantial increases in blood urea nitrogen (45.48 ± 8.13), serum creatinine (1.39 ± 0.19), cystatin C (2.68 ± 0.39), and KIM-1 (2.60 ± 0.52). These values were significantly attenuated by co-treatment with BCA (20 and 40 mg/kg). VAN also produced oxidative stress, inflammatory responses, histopathological damage, elevated expression of JAK2, STAT3, and caspase-3, and decreased expression of GPX4. BCA significantly decreased kidney damage, restored redox homeostasis, reduced inflammatory cytokines levels, and apoptosis, suppressed JAK2/STAT3 activation and upregulated GPX4 expression. BCA reduced VAN-induced kidney injury, oxidative stress, inflammation, and apoptosis-associated signaling in mice, indicating that the nephroprotective action of BCA may be mediated by JAK2/STAT-3/GPX4 signaling pathways. However, more molecular and functional confirmation is needed.