Deciphering the molecular mechanism of NLRP3 in BPA-mediated toxicity: Implications for targeted therapies

Bisphenol-A (BPA), a pervasive industrial chemical used in polymer synthesis, is found in numerous consumer products including food packaging, medical devices, and resins. Detectable in a majority of the global population, BPA exposure occurs via ingestion, inhalation, and dermal routes. Extensive research has demonstrated the adverse health effects of BPA, particularly its disruption of immune and endocrine systems, along with genotoxic potential. This review focuses on the complex relationship between BPA exposure and the NOD-like receptor protein 3 (NLRP3) inflammasome, a multiprotein complex central to inflammatory disease processes. We examine how BPA induces oxidative stress through the generation of intracellular free radicals, subsequently activating NLRP3 signaling. The mechanistic details of this process are explored, including the involvement of signaling cascades such as PI3K/AKT, JAK/STAT, AMPK/mTOR, and ERK/MAPK, which are implicated in NLRP3 inflammasome activation. A key focus of this review is the wide-ranging organ toxicities associated with BPA exposure, including hepatic, renal, gastrointestinal, and cardiovascular dysfunction. We investigate the immunopathogenesis and molecular pathways driving these injuries, highlighting the interplay among BPA, oxidative stress, and the NLRP3 inflammasome. Finally, this review explores the emerging concept of targeting NLRP3 as a potential therapeutic strategy to mitigate the organ toxicities stemming from BPA exposure. This work integrates current knowledge, emphasizes complex molecular mechanisms, and promotes further research into NLRP3-targeted interventions.