Bisphenol S-induced chronic inflammatory stress in liver via peroxisome proliferator-activated receptor γ using fish in vivo and in vitro models.

Bisphenol S (BPS) has been widely used as a bisphenol alternative in recent few years. However, with mounting evidence suggesting that the presence of BPS in the environment also poses risks to ecosystems and human health, we decided to use the juvenile common carp (Cyprinus carpio) and its primary macrophages as in vivo and in vitro models to examine if BPS is a safe substitute of BPA. The present study evaluated the immune responses of chronic BPS exposure and their mechanisms of action associated with peroxisome proliferator-activated receptor (PPAR) signaling pathway. Potential oxidative stress and pro-inflammatory effects of BPS exposure were identified in fish liver after 60-day exposure, based on the increased reactive oxygen species (ROS) production, antioxidant capacity, NO production, lipid peroxidation, and induction of inflammatory cytokine expression, as well as acute phase protein levels of C-reactive protein, immunoglobulin M, lysozyme, and complement component 3. Moreover, pparγ, PPAR pathway-associated genes retinoid x receptor α (rxrα) and nuclear factor-κb (nfκb) presented a rough concentration-dependent alteration after BPS exposure. An acute BPS exposure to the isolated primary macrophages from juvenile common carp was performed to help elucidate gene expression patterns of pparγ, rxrα, and nfκb in a typical immune cell model, the results were consistent with what we found in vivo experiments for long-term BPS exposure. Furthermore, with coexposure to BPS and a PPARγ antagonist, the restriction of PPAR signaling pathway significantly inhibited the induction of ROS and the mRNA level of interleukin-1β, confirming the involvement of PPAR pathway in BPS-induced chronic inflammatory stress in liver.