Objective:

To investigate whether Biochanin A (BCA) can mitigate doxorubicin (DOX)-induced cardiac injury in rats and explore the underlying molecular mechanisms.

Approach:

• Study Design: Male Wistar rats were assigned to control, BCA-alone, DOX-alone, and DOX combined with BCA (25 or 50 mg/kg) groups.
• Assessment Methods: Electrocardiographic parameters were recorded, and serum cardiac biomarkers (CK-MB, LDH, troponin) were measured. Cardiac tissue was evaluated for oxidative stress markers, antioxidant enzyme activities, inflammatory mediators, and apoptotic gene expression.
• Molecular Analysis: The involvement of PI3K/Akt/mTOR, p38 MAPK, and PTEN signaling pathways was assessed using molecular analyses.

Key Findings:

• DOX administration caused significant ECG abnormalities and elevated serum cardiac biomarkers.
• BCA treatment attenuated alterations caused by DOX, with greater effects observed at the higher dose.
• BCA improved antioxidant status and reduced inflammatory and apoptotic marker expression.
• BCA altered PI3K/Akt/mTOR and p38 MAPK pathway-marker immunoreactivity compared to the DOX group.

Interpretation:

Biochanin A alleviated acute DOX-induced cardiotoxicity in rats and was associated with modulation of oxidative stress, inflammatory, and apoptotic markers.

Limitations:

• The study was conducted in a rat model, which may not fully replicate human responses.
• Long-term effects and clinical applicability of BCA were not assessed.

Conclusion:

BCA may represent a potential cardioprotective strategy in acute anthracycline-associated cardiac injury.