Toxic Effects of Bisphenol S Showing Immunomodulation in Fish Macrophages

Bisphenol S (BES), a structural analogue of bisphenol A (BPA), has been increasingly used as a common replacement of BPA due to health concerns regarding the former. However, mounting evidence suggests, that BPS has similar endocrine-disrupting effects as BPA, and likewise, its presence in the environment may :pose considerable risks to ecosystems and human health. Using fish primary macro-phageS (fpMQs), we here evaluated the immunothodulatory effects of BPS and its mechanisms, of action associated with estrogen receptors (ERs). Following BPS exposure at environmentally relevant concentrations from 0.1 to 1000 mu g/l. we observed approximate concentration-dependent increases in nitric oxide and reactive oxygen species generation and total antioxidant capacity as well as the gene expression of inflammatory cytokines in fpMQs. BPS impaired phagocytic capability but enhanced fpMQ activation levels in response to lipopolysaccharide stimulation and promoted apoptosis, indicating an impact on cell functions. At a concentration of 100 mu g/L, BPS and BPA showed comparable pro-inflammatory. potential with both up-regulating the production of free radicals and cytokine expression; however, BPS had no significant potency with regard's to inducing lipid peroxidation and apoptosis, different from BPA's effects. Moreover, BPS induced both era and er,62 expression in fpMQs, whereas BPA induced only era expression. This study demonstrates that, similarly to BPA, exposure to low doses of BPS significantly disturbs the immune response of fpMQs in vitro and first reveals overlapping but different roles of ERs in response to BPS and BPA.