Effects of single or combined exposure to bisphenol A and mono(2-ethylhexyl)phthalate on oxidant/antioxidant status, endoplasmic reticulum stress, and apoptosis in HepG2 cell line

Özkemahlı, Gizem; Erkekoğlu, Pınar; Ercan, Ayse B.; Zeybek, Naciye Dilara; Yersal, Nilgün; Koçer-Gümüşel, Belma

doi:10.1007/s11356-022-22937-6

Cited by 10 publications

(8 citation statements)

References 74 publications

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“…Morphological alterations in cells exposed to BPA were demonstrated in HepG2 cells with a round shape, less cell number, and loss of connections with neighboring cells. 27 Additionally, BPA exposure changed the typical morphology of human retinoblastoma Y79 cells 28 and caused structural and developmental defects in beta cells. 29 Human lung carcinoma cells (A549) treated with BPA for 72 h displayed multiple morphological changes, including loss of adherent phenotype and reduction in cell-to-cell contacts.…”

Section: Discussionmentioning

confidence: 99%

“…The toxic effect of BPA was evident from the morphological data compared with untreated cells (Figure 1). Morphological alterations in cells exposed to BPA were demonstrated in HepG2 cells with a round shape, less cell number, and loss of connections with neighboring cells 27 . Additionally, BPA exposure changed the typical morphology of human retinoblastoma Y79 cells 28 and caused structural and developmental defects in beta cells 29 .…”

Section: Discussionmentioning

confidence: 99%

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Bisphenol A promotes cell death in healthy respiratory system cells through inhibition of cell proliferation and induction of G2/M cell cycle arrest

Aysin

2024

Environmental Toxicology

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Bisphenol A (BPA) is a substance that can harm the environment and human health by interfering with the normal functioning of the body's hormonal system. It is commonly found in various plastic‐based products such as cosmetics, canned foods, beverage containers, and medical equipment and as well as it can also be absorbed by inhalation. There have been limited studies on the effects of BPA on lung fibroblasts, and it is still unclear how high levels of BPA can impact respiratory system cells, particularly the lungs and trachea. In this research, we aimed to investigate the cell cycle disruption potential of BPA on respiratory system cells by examining healthy trachea and lung cells together for the first time. The findings indicated that BPA exposure can alter the healthy cells' morphology, leading to reduced cellular viability that has been assessed by MTT and SRB assays. BPA treatment was able to activate caspase3 as expected, which could cause apoptosis in treated cells. Although the highest dose of BPA did not increase the apoptotic rate of rat trachea cells, it remarkably caused them to become necrotic (52.12%). In addition to quantifying the induction of apoptosis and necrosis by BPA, cell cycle profiles were also determined using flow cytometry. Thereby, BPA treatment unexpectedly inhibited the cell cycle's progression by causing G2/M cell cycle arrest in both lung and tracheal cells, which hindered cell proliferation. The findings of the study suggested that exposure to BPA could lead to serious respiratory problems, even respiratory tract cancers via alterations in the cell cycle.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bisphenol A promotes cell death in healthy respiratory system cells through inhibition of cell proliferation and induction of G2/M cell cycle arrest

Aysin

2024

Environmental Toxicology

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“…ER stress is considered an intermediate pathway to induce the other pathways and damage cells during BPA exposure. Single or combined exposure to BPA and mono(2-ethylhexyl) phthalate cause serious toxicological outcomes in the HepG2 cell line, including altered oxidant/antioxidant status, aggravated ER stress, and apoptosis [ 61 ]. BPA exposure induces neurotoxicity in rats involved with neuronal ER stress, apoptosis, and JAK1/STAT1 signaling pathway [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

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

Pan

Huang

et al. 2023

IJMS

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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.

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“…The exact way underlying DEHP's disruption of DNA methylation is not yet understood. However, previous studies have shown that MEHP can cause oxidative DNA damage in human tissue cultures [41,42]. DNA damage caused by oxidative stress may potentially disrupt proteins that bind to methylated cytosine and guanine residues and alter the function of DNA methyltransferases, leading to epigenetic modi cations [43].…”

Section: Discussionmentioning

confidence: 99%

The role of angiotensin I-converting enzyme gene polymorphism and global DNA methylation in the negative associations between urine di-(2-ethylhexyl) phthalate metabolites and serum adiponectin in a young Taiwanese population

Lin

Lee

Chen

et al. 2023

Preprint

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Background Adiponectin is a key protein produced in adipose tissue, with crucial involvement in multiple metabolic processes. Di-(2-ethylhexyl) phthalate (DEHP), one of the phthalate compounds used as a plasticizer, has been shown to decrease adiponectin levels in vitro and in vivo studies. However, the role of angiotensin I-converting enzyme (ACE) gene polymorphism and epigenetic changes in the relationship between DEHP exposure and adiponectin levels is not well understood. Methods This study examined the correlation between urine levels of DEHP metabolite, epigenetic marker 5mdC/dG, ACE gene phenotypes, and adiponectin levels in a sample of 699 individuals aged 12 to 30 from Taiwan. Results Results showed a positive relationship between mono-2-ethylhexyl phthalate (MEHP) and 5mdC/dG, and a negative association between both MEHP and 5mdC/dG with adiponectin. The inverse relationship between MEHP and adiponectin was stronger when 5mdC/dG levels were above the median, as indicated by a smaller regression coefficient (-0.095 compared to -0.049). The structural equation model (SEM) analysis indicated that MEHP has a direct inverse effect on adiponectin and an indirect effect via 5mdC/dG. Subgroup analysis revealed a negative correlation between MEHP and adiponectin in individuals with the I/I ACE genotype, but not in others. Conclusions In this young Taiwanese population, our findings suggest that urine MEHP levels are negatively correlated with serum adiponectin levels and that ACE gene polymorphism and epigenetic modifications may play a role in this association. Further study is needed to validate these results and determine causality.

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Effects of single or combined exposure to bisphenol A and mono(2-ethylhexyl)phthalate on oxidant/antioxidant status, endoplasmic reticulum stress, and apoptosis in HepG2 cell line

Cited by 10 publications

References 74 publications

Bisphenol A promotes cell death in healthy respiratory system cells through inhibition of cell proliferation and induction of G2/M cell cycle arrest

Bisphenol A promotes cell death in healthy respiratory system cells through inhibition of cell proliferation and induction of G2/M cell cycle arrest

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

The role of angiotensin I-converting enzyme gene polymorphism and global DNA methylation in the negative associations between urine di-(2-ethylhexyl) phthalate metabolites and serum adiponectin in a young Taiwanese population

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