Protective Effects of Selenium Nanoparticles against Bisphenol A-Induced Toxicity in Porcine Intestinal Epithelial Cells

Abstract

Bisphenol A (BPA) is widely used to harden plastics and polycarbonates and causes serious toxic effects in multiple organs, including the intestines. Selenium, as an essential nutrient element for humans and animals, exhibits a predominant effect in various physiological processes. Selenium nanoparticles have attracted more and more attention due to their outstanding biological activity and biosafety. We prepared chitosan-coated selenium nanoparticles (SeNPs) and further compared the protective effects, and investigated the underlying mechanism of SeNPs and inorganic selenium (Na2SeO3) on BPA-induced toxicity in porcine intestinal epithelial cells (IPEC-J2). The particle size, zeta potential, and microstructure of SeNPs were detected by using a nano-selenium particle size meter and a transmission electron microscope. IPEC-J2 cells were exposed to BPA alone or simultaneously exposed to BPA and SeNPs or Na2SeO3. The CCK8 assay was performed to screen the optimal concentration of BPA exposure and the optimal concentration of SeNPs and Na2SeO3 treatment. The apoptosis rate was detected by flow cytometry. Real-time PCR and Western blot methods were used to analyze the mRNA and protein expression of factors related to tight junctions, apoptosis, inflammatory responses and endoplasmic reticulum stress. Increased death and morphological damage were observed after BPA exposure, and these increases were attenuated by SeNPs and Na2SeO3 treatment. BPA exposure disturbed the tight junction function involved with decreased expression of tight junction protein Zonula occludens 1 (ZO-1), occludin, and claudin-1 proteins. Proinflammatory response mediated by the transcription factor nuclear factor-k-gene binding (NF-κB), such as elevated levels of interleukin-1β(IL-1β), interleukin-6 (IL-6), interferon-γ (IFN-γ), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α) expression was induced at 6 and 24 h after BPA exposure. BPA exposure also disturbed the oxidant/antioxidant status and led to oxidative stress. IPEC-J2 cell apoptosis was induced by BPA exposure, as indicated by increased BCL-2-associated X protein (Bax), caspase 3, caspase 8, and caspase 9 expression and decreased B-cell lymphoma-2 (Bcl-2) and Bcl-xl expression. BPA exposure activated the endoplasmic reticulum stress (ERS) mediated by the receptor protein kinase receptor-like endoplasmic reticulum kinase (PERK), Inositol requiring enzyme 1 (IRE1α), and activating transcription factor 6 (ATF6). We found that treatment with SeNPs and Na2SeO3 can alleviate the intestinal damage caused by BPA. SeNPs were superior to Na2SeO3 and counteracted BPA-induced tight junction function injury, proinflammatory response, oxidative stress, apoptosis, and ERS stress. Our findings suggest that SeNPs protect intestinal epithelial cells from BPA-induced damage, partly through inhibiting ER stress activation and subsequently attenuating proinflammatory responses and oxidative stress and suppressing apoptosis, thus enhancing the intestinal epithelial barrier function. Our data indicate that selenium nanoparticles may represent an effective and reliable tool for preventing BPA toxicity in animals and humans.

New insights into the unfolded protein response (UPR)-anterior gradient 2 (AGR2) pathway in the regulation of intestinal barrier function in weaned piglets

“…1 ). Previous studies showed that the protective effects of selenium nanoparticles (SeNPs) on intestinal barrier dysfunction are closely associated with ERS-related PERK-eIF2α-ATF4-CHOP signaling pathway in vitro ( Pan et al., 2023 ; Song et al., 2022b ) and in vivo ( Qiao et al., 2022 ). A mouse model with eIF2α mutations in IECs showed increased susceptibility to dextran sulfate sodium (DSS) induced and Salmonella infection-associated colitis ( Hooper et al., 2019 ).…”

“…The ATF6/CHOP pathway may be associated with intestinal barrier dysfunction during sepsis ( Wang et al., 2022 ). Many studies have shown that inhibition of ATF6 expression can relieve ER stress and exert protective effects on the intestinal barrier function of SeNPs ( Pan et al., 2023 ), chlorogenic acid ( Song et al., 2022a ), and berberine ( Gong et al., 2022 ). These findings underscore the importance of ATF6 signaling in intestinal barrier function.…”

Se Alleviated Pb-Caused Neurotoxicity in Chickens: SPS2-GPx1-GSH-IL-2/IL-17-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury

“…For example, a reduction in IL-2 , an elevation in IL-4 and IL-12β , and inflammatory damage caused by Pb were mitigated by Se in chicken testes [ 10 ] and hearts [ 14 ]. Se treatment alleviated bisphenol A-caused IL-6 and IL-17 elevation and inflammatory response in IPEC-J2 cells [ 15 ], as well as relieved Pb-caused IL-6 and NO increase and inflammatory response in RAW264.7 macrophages [ 13 ]. Thus, we assumed that Se has an anti-inflammatory function under Pb stress in chicken Ces and Thi through the measurement of IL-2 , IL-4 , IL-6 , IL-12β , IL-17 , INF-γ , and NO.…”