Exosomes improved oxidative stress and apoptosis in BPA-induced nephrotoxicity in kidney cells through modulation of Nrf2/Keap1 signaling pathway

Abstract

Bisphenol A (BPA) is an environmental toxicant known to induce nephrotoxicity primarily through oxidative stress–mediated inflammation and apoptosis. Mesenchymal stem cell-derived exosomes have recently emerged as promising cell-free therapeutic agents with antioxidant and anti-apoptotic properties. This study aimed to investigate the protective effects of bone marrow mesenchymal stromal cell-derived exosomes against BPA-induced nephrotoxicity in human proximal tubular epithelial (HK-2) cells, with particular emphasis on the potential involvement of the Nrf2/Keap1 signaling pathway. HK-2 cells were allocated into four groups: control, BPA, exosome (EXO), and BPA + EXO. Cell viability was assessed using the MTT assay. Intracellular reactive oxygen species (ROS), lipid peroxidation, antioxidant parameters, total antioxidant capacity (TAC), glutathione (GSH) levels, and inflammatory cytokines (IL-6 and IL-10) were evaluated using standard biochemical assays. Protein expression levels of Nrf2, Keap1, Bax, and Bcl-2 were determined by Western blot analysis. BPA exposure significantly reduced cell viability and antioxidant capacity while increasing ROS production, lipid peroxidation, pro-inflammatory cytokine release, and apoptotic signaling. Exosome treatment markedly attenuated oxidative stress, restored antioxidant defenses, improved inflammatory cytokine balance, and reversed BPA-induced alterations in Nrf2/Keap1 signaling and apoptosis-related protein expression. Bone marrow mesenchymal stromal cell-derived exosomes exert protective effects against BPA-induced cytotoxicity in HK-2 cells by alleviating oxidative stress, modulating the Nrf2/Keap1 signaling pathway, and suppressing apoptosis. Although further mechanistic studies are required to establish causality, these findings highlight the therapeutic potential of exosomes as a cell-free strategy for mitigating environmental toxin-associated renal injury.