Mechanistic insights into the cardioprotective effects of Biochanin A against cisplatin-induced toxicity: the role of oxidative stress and the Nrf2 signaling pathway

Background and aim Cisplatin (CP) is an anti-tumor drug with cardiotoxicity side effects. This study aimed to evaluate the cardioprotective effect of Biochanin A against CP-induced cardiotoxicity in mice.Experimental approach Male mice (n = 50) were divided into five groups: control, CP only, low-dose Biochanin A (50 mg/kg) + CP, high-dose Biochanin A (100 mg/kg) + CP, and Biochanin A only (100 mg/kg). Histopathological, cardiac, and oxidative stress markers), inflammatory cytokines, and the p62-Keap1-Nrf2 signaling pathway were used to assess CP-induced cardiac injury.Key findings Biochanin A ameliorated CP-induced histopathological alteration, including immuno-inflammatory infiltration, apoptosis, and myocardial edema (p = 0.0031). CTnI, CK, and LDH levels for the high-dose Biochanin A group were also significantly lowered (p = 0.0023, 0.0041, 0.0037, respectively). Antioxidant enzyme (SOD, CAT, GSH) levels were significantly elevated, and MDA levels were significantly reduced (p = 0.007, 0.004, 0.005, 0.002, respectively). The levels of TNF-α and IL-6 were markedly reduced by Biochanin A treatment (p = 0.034, 0.029, respectively). Bochanin A treatment significantly enhanced the Nuclear translocation of Nrf2 and downregulated its inhibitor Keap1 (p = 0.0034, 0.0018, respectively), activating the Nrf2 signaling pathway.Conclusion Biochanin A demonstrates promise as a therapeutic agent to prevent CP-induced cardiotoxicity, potentially allowing for safer and more effective chemotherapy regimens.