Toxic Effects of Bisphenol S Showing Immunomodulation in Fish Macrophages

Abstract

Bisphenol S (BPS), 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 macrophages (fpMQs), we here evaluated the immunomodulatory 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 μg/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 μg/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 regards to inducing lipid peroxidation and apoptosis, different from BPA's effects. Moreover, BPS induced both erα and erβ2 expression in fpMQs, whereas BPA induced only erα 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.

Toxicity and multigenerational effects of bisphenol S exposure to Caenorhabditis elegans on developmental, biochemical, reproductive and oxidative stress

“…83 Qiu et al also found that BPS could cause severe oxidative stress at higher BPS exposure concentrations, subsequently destroying cell homeostasis and promoting apoptosis. 13 Based on our studies, we hypothesized that BPS may affect apoptosis by oxidative stress and thus affect the lifespan of C. elegans.…”

“…[8][9][10] Bisphenol S is a structural analog of bisphenol A which is widely used as a substitute in a variety of products such as baby bottles, thermal receipt paper, food packaging materials and personal care products. 2,[11][12][13] In Europe, the annual production of BPS is between 1000 and 10 000 t, and steadily increases. 14 In 2013, the detection concentration of BPS in Taihu Lake was 2 ng L −1 .…”

Modulation of cytokine/chemokine production in human macrophages by bisphenol A: A comparison to analogues and interactions with genistein

“…Moreover, BPA, BPS, and BPAF differentially recruit co-regulators to the bisphenol-ER-a complex; this could be one possible reason for differential biological actions induced by these agents. Qiu et al (2018) showed that INFc,TNFa, mRNA expression in association with increased expression of both ER-a and -b in fish primary macrophages (isolated from head kidney of Cyprinus carpio). BPA-induced ER-a signaling can lead to increased activation of ERK/MAPK and PI3K/AKT pathways (e.g.…”

Expression of pro‐inflammatory cytokines and mediators induced by Bisphenol A via ERK‐NFκB and JAK1/2‐STAT3 pathways in macrophages

“…These evidences show that LPS‐induced macrophage activation can be inhibited by BPA. In contrast, expression of proinflammatory cytokines including IL‐1β, TNFα, and IL‐6 are induced by BPA in human macrophages, THP‐1 cells, and fish macrophages . Generation of NO and expression of iNOS is induced by BPA in fish macrophages .…”