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Epidemiological studies have suggested a correlation between bisphenol A (BPA) and type 2 diabetes (T2DM). The effects of BPA on β-cell dysfunction may reveal the risks from an in vitro perspective. We used the rat insulinoma (INS-1) cell lines (a type of β-cells) to set up normal or damaged models (DM), which were exposed to various concentrations of BPA (0.001, 0.01, 0.1, 1, 10 and 100 μM). An increase in reactive oxygen species (ROS) and apoptosis, and a decrease in cell viability were observed in INS-1 cells exposed to high doses of BPA for 48 h. Interestingly, exposure to lower doses of BPA for 24 h resulted in increased ROS levels and apoptosis rates in INS-1 in the DM group, along with decreased cell viability, suggesting that BPA exerts toxicity to INS-1 cells, particularly to the DM group. Insulin levels and Glut2 expression, glucose consumption, intracellular Ca2+ and insulin secretion were increased in INS-1 cells after 48 h exposure to high dose of BPA. Stronger effects were observed in the DM group, even those exposed to low doses of BPA for 24 h. Moreover, BPA inhibited high glucose-stimulated insulin secretion in these cells. Our research suggests that low doses of BPA exacerbate the dysfunction caused by glucolipotoxicity, implying environmental BPA exposure poses a risk for individuals with prediabetes or T2DM. [Display omitted] • High doses of BPA induce toxicity and compensatory secretion of insulin in normal INS-1cells. • Low doses of BPA accelerate the deterioration of dysfunctional INS-1cells. • Environmental BPA exposure increase the risk for dysfunction of β-cells. • Individuals susceptible to T2DM should avoid exposure to BPA. [ABSTRACT FROM AUTHOR]

[Display omitted] Bisphenol A (BPA) induces neurotoxicity via enhancing cell apoptosis and inflammation potently (effective at nanomolar concentrations), but its mechanisms remain unidentified. In this study, human neuroblastoma cell lines, IMR-32 and SK-N-SH cells, isolated from a male and a female subject, respectively, were exposed to BPA at various concentrations, with epigallocatechin gallate (EGCG, an antioxidant from green tea), Z-YVAD-FMK (a caspase-1 inhibitor), and ICI182.780 [an estrogen receptor (ER) inhibitor] as modulators. The results showed that BPA increased the mRNA levels of IL-18, ASC, GSDMD and protein levels of NLRP3, caspase-1 and GSDMD in both cell lines in a nonlinear manner. Noticeably, the direction of changes in the mRNA levels of caspase-1 and IL-1β were opposite, so did each of them in different cell lines: caspase-1 was enhanced in IMR-32 cells but suppressed in SK-N-SH cells, while IL-1β was suppressed in IMR-32 cells but enhanced in SK-N-SH cells. The level of GSDMD in situ increased along with the leakage of IL-1β, IL-18, caspase-1 and lactate dehydrogenase (LDH). Moreover, all the above effects of BPA were reversed by Z-YVAD-FMK, ICI182.780, and EGCG. Besides, BPA significantly increased reactive oxygen species production, LDH leakage and apoptosis, with reduced cell viability and mitochondrial membrane potential, in both cell lines, whereas Z-YVAD-FMK and ICI182.780 significantly alleviated the induction of Bak1, Bax, Bcl-2 and caspase-3 proteins by BPA. In summary, BPA may induce pyroptosis in neuroblastoma cells through NLRP3/caspase-1/GSDMD pathway, as mediated by ER; caspase-1-dependent pyroptosis may also contribute to BPA-induced apoptosis, an effect alleviated by EGCG. [ABSTRACT FROM AUTHOR]

Epidemiological studies have shown that cardiovascular diseases caused by PM 2.5 pollution account for the second death rate in China. Polycyclic aromatic hydrocarbons (PAHs) are one important group of persistent organic pollutants absorbed on PM 2.5. Though individual PAH is related to vascular disease, the relationship between environmental PAHs exposure and vascular damages is still unclear. To explore the effect of PAHs on blood vessel, human umbilical vein endothelial cells (HUVECs) are treated with 16 priority–controlled PAHs at various concentrations to study their cytotoxicity and morphological alteration. Results showed that, after 48 h treatment, PAHs mixture generally attenuated the ability of wound healing, transwell migration and tube formation of HUVECs (p < 0.01) except for 1 × PAHs in transwell migration. Moreover, PAHs increased the levels of ROS and 8-hydroxy-2′-deoxyguanosine (p < 0.05), indicating that it exceeded the scavenging ability of superoxide dismutase activity. However, PAHs mixture did not increase apoptosis rate, which may be attribute to the difference of PAH concentration and composition between this study and previous reports. Downstream signaling cascades significantly and generally upregulated the relative expression of proteins in Nrf2/HO-1 and NF-ƙB/TNF- α pathway with the activation of oxidative stress, including HO-, TNF- α and Nrf2. In summary, this study suggests that environmental mixture of 16 priority-controlled PAHs can induce the damages of vascular endothelial cells involved in cellular oxidative stress and inflammation. [Display omitted] • Environmental dose PAHs mixture can induce the damages of HUVECs. • Oxidative stress and inflammation involve the damages of HUVECs exposed to PAHs. • PAHs may be the dominant compounds on PM 2.5 which increase the occurrence of CVD. [ABSTRACT FROM AUTHOR]