Bisphenol A–Induced Nephrotoxicity: Mechanistic Insights Into Oxidative Stress, Inflammation, and Cellular Dysfunction

Abstract

Bisphenol A (BPA), a prevalent endocrine disruptor and component of synthetic resins, has recently gained attention for its nephrotoxic potential. Experimental evidence demonstrates that BPA induces kidney injury through oxidative stress, inflammation, and apoptosis. BPA exposure leads to excessive production of reactive oxygen species, increased lipid peroxidation, and decreased levels of key antioxidant enzymes such as superoxide dismutase, catalase, and glutathione, resulting in redox imbalance. Concurrently, BPA activates inflammatory cytokines, including IL‐1β, IL‐6, and TNF‐α, as well as the NF‐κB signaling pathway, which contribute to renal inflammation and tissue injury. Histopathological analyses consistently reveal glomerular congestion, tubular degeneration, and necrosis. In vitro studies further demonstrate reduced renal cell viability and enhanced apoptosis mediated by the activation of PI3K/AKT, Bcl2/Bax–caspase, and AMPK/mTOR signaling pathways. Collectively, these findings highlight BPA's ability to cause both structural and functional damage to the kidney through oxidative and inflammatory cascades. Despite advances in understanding BPA‐induced nephrotoxicity, translating experimental findings to human health remains challenging due to interspecies variations, differing exposure routes, and inconsistent epidemiological data. Moreover, growing evidence suggests that BPA substitutes, such as bisphenol F and bisphenol S, possess similar endocrine‐disrupting and nephrotoxic effects, raising further safety concerns. Future research should focus on elucidating mechanisms underlying BPA‐induced cell cycle arrest, its long‐term effects on renal repair, and susceptibility factors such as genetic and sex‐specific differences. Addressing these gaps is essential for improving risk assessment and guiding regulatory measures to mitigate BPA‐related kidney dysfunction.