Boric Acid Protects against Bisphenol A–induced Hematotoxicity and Neurotoxicity: An Integrated In Vivo and Network Pharmacology Approach

Abstract Purpose Bisphenol A (BPA) is a widely used industrial chemical that can induce oxidative stress, hematotoxicity, and neurotoxicity via mitochondrial dysfunction and apoptosis. This study evaluated whether boric acid (BA) mitigates BPA-induced systemic injury in male Wistar rats using integrated in vivo and network analyses. Methods Forty-two rats were assigned to six groups and treated for 28 days with BPA (130 mg/kg/day, oral), BA (100 or 200 mg/kg/day, i.p.), or combinations. Results BPA markedly increased total oxidant status (TOS) and oxidative stress index (OSI) and reduced total antioxidant status (TAS), indicating severe redox imbalance. BPA also decreased RBC, PLT, Hb, Hct, and bone marrow nucleated cells, consistent with myelosuppression. In brain tissue, BPA increased Bax, caspase-3, and cytochrome c immunoreactivity while decreasing Bcl-2, accompanied by neuronal degeneration and necrosis. BA co-treatment improved TAS, reduced OSI, restored hematological indices and BMNC counts, and attenuated pro-apoptotic signalling in a dose-dependent manner, with BA (200 mg/kg) showing the strongest protection. Network pharmacology highlighted BPA-associated neuroactive ligand–receptor interactions and BA-associated antioxidant and DNA repair modules, with enrichment of oxidative stress response, apoptotic regulation, and DNA damage repair pathways. Conclusion Collectively, BA reduced BPA-induced oxidative stress, hematological suppression, and neuronal apoptosis in rats, supporting its protective potential as a redox-modulating adjunct in BPA exposure models.