Bisphenol A Group Research Articles

THE EFFECT OF QUERCETIN ON SOME HEMATOLOGICAL PARAMETERS AGAINST BISPHENOL-A EXPOSURE IN STREPTOZOCIN-INDUCED RATS

Bisphenol-A (BPA) is an endocrine-disrupting environmental toxin widely used in the composition of plastics. Today, the widespread use of BPA in preserving and packaging food and beverages increases BPA exposure. Therefore, recent research has focused on the health effects of continuous exposure to BPA. This study aimed to investigate the protective effect of quercetin (QUE) on different hematologic variables in rats induced by the environmental toxin BPA and streptozocin (STZ). Wistar albino rats were administered BPA orally (p.o.) at 10 mg/kg and QUE intraperitoneally (i.p.) at 15 mg/kg for 14 days. STZ was administered subcutaneously (s.c.) in a single dose of 50 mg/kg at the beginning of the experiment. 72 rats were randomly selected for the experimental procedure and divided into 9 groups with 8 animals in each group. The groups were created as follows; Group 1: Control (Saline); Group 2: Corn oil (0.5 ml, solvent); Group 3: STZ (50 mg/kg); Group 4: BPA (10 mg/kg); Group 5: QUE (15mg/kg); Group 6: STZ (50 mg/kg) + QUE (15mg/kg); Group 7: BPA (10 mg/kg) + QUE (15mg/kg); Group 8: STZ (50 mg/kg) + BPA group (10 mg/kg); Group 9: STZ (50 mg/kg) + BPA (10 mg/kg) + QUE (15mg/kg). STZ and BPA-treated rats showed functional variability in all hematologic parameters. The combination of STZ and BPA significantly reduced erythrocytes, leukocytes, and their associated parameters. However, QUE treatment alone or in combination corrected the altered hematologic parameters. The results of this study demonstrated that exposure to BPA in combination with STZ may alter hematologic indices, while QUE may be a therapeutic agent to correct the altered blood profile.

Ameliorative Effects of Zinc Oxide, in Either Conventional or Nanoformulation, Against Bisphenol A Toxicity on Reproductive Performance, Oxidative Status, Gene Expression and Histopathology in Adult Male Rats

Bisphenol A (BPA) is a widely used endocrine disruptor that represents a significant risk to male reproductive function. Zinc (Zn) is vital for appropriate development of testes and to guarantee optimal testicular function and spermatogenesis. Our goal was to investigate if zinc oxide (ZnO), either in conventional or nanoformulation, could safeguard adult male rats’ reproductive performance against the damaging effects of BPA. Signaling expression of CYP11A1 and Nrf-2 in the testis, testicular oxidant-antioxidant status, Bax/Bcl-2 apoptotic ratio, and histological examination of various reproductive organs were all evaluated. Twenty-eight adult male albino rats were divided randomly into 4 groups (7 animals each) including the control, BPA, conventional zinc oxide (cZnO) + BPA, and zinc oxide nanoparticles (ZnO-NPs) + BPA groups. The study was extended for 2 successive months. Our findings revealed strong negative effects of BPA on sperm cell characteristics such as sperm motility, viability, concentration and abnormalities. Additionally, BPA reduced serum levels of testosterone, triiodothyronine (T3), and thyroxine (T4). Also, it evoked marked oxidative stress in the testes; elevating malondialdehyde (MDA) and reducing total antioxidant capacity (TAC). BPA significantly downregulated testicular mRNA relative expression levels of CYP11A1 and Nrf-2, compared to control. Testicular apoptosis was also prompted by increasing Bax/ Bcl-2 ratio in testicular tissue. Histopathological findings in the testes, epididymis, prostate gland, and seminal vesicle confirmed the detrimental effects of BPA. Interestingly, cZnO and ZnO-NPs significantly alleviated all negative effects of BPA, but ZnO-NPs performed better. In conclusion, our findings point to ZnO, specifically ZnO-NPs, as a viable treatment for BPA-induced testicular dysfunction.

Bisphenol-A exposure alters liver, kidney, and pancreatic Klotho expression by HSP60-activated mTOR/autophagy pathway in male albino rats.

The effect of bisphenol-A (BPA) on Klotho protein (aging-suppressing protein) expression in different body organs has not been sufficiently addressed by literature studies. The study investigated the impact of BPA on Klotho expression in multiple organs including the liver, kidney, and pancreas and suggested the involved molecular pathways. Twenty-seven male Wistar albino rats were divided into 3 equal groups: control, low-dose BPA (4.5 µg/L), and high-dose BPA (8 µg/L) groups in drinking water for 45 consecutive days. Liver, kidney, and pancreatic specimens were prepared for a gene study of Klotho, HSP60, mTOR, and ULK1 mRNA expressions. Also, the tissue specimens were measured for malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels. Paraffin-embedded sections were also prepared and subjected to Hematoxylin and Eosin (H&E) staining and immunohistochemical detection of Klotho and HSP60. The results revealed an alteration in the MDA, SOD, NO tissue levels, disturbed gene expression profile, and apoptotic changes in the histological findings of the examined organs which were obvious (p < 0.05) in the high-dose group. The anti-aging Klotho gene/protein expression was reduced (p < 0.05) more in the high-dose BPA group than in the low dose. In contrast, HSP60 gene/protein expression was significantly increased (p < 0.05) more in the high dose. It was concluded that BPA exposure contributed to cell stress and markedly reduced Klotho protein expression in liver, kidney, and pancreatic tissues, possibly by modulation of the HSP60-activated mTOR/autophagy signaling.

Important roles of Hif1a in maternal or adult BPA exposure induced pancreatic injuries

Bisphenol A (BPA) is a monomer to produce polycarbonate plastics and can be released into the environment through human activities, leading to its accumulation in animals, plants and humans through direct contact or environmental exposure. Epidemiological studies have reported that BPA exposure is associated with metabolic disorders. The pancreas is an important endocrine organ and plays an important role in metabolic disorders. To explore the possible long-term effects of BPA exposure on neonatal health, bioinformatic methods were used to identify differentially expressed genes (DEGs) by comparing the neonatal pancreas after maternal exposure to BPA with the adult pancreas after direct exposure to BPA. Two datasets about BPA exposure and pancreatic abnormality, GSE82175 and GSE126297 in Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) were collected. Control (or BPA-exposed) offspring (maternal exposure) and Control (or BPA-exposed) adults (direct exposure) were defined as Control (or BPA) groups. The results showed that BPA disturbed the normal function of the pancreas in both offspring and adults, with offspring showing higher susceptibility to BPA than adults. Seventeen insulin secretion-related DEGs (Stxbp5l, Fam3d, Mia3, Igf1, Hif1a, Aqp1, Kif5b, Tiam1, Map4k4, Cyp51, Pde1c, Rab3c, Arntl, Clock, Edn3, Kcnb1, and Krt20) in the BPA group were identified, and 15 regulator DEGs (Zfp830, 4931431B13Rik, Egr1, Ddit4l, Cep55, G530011O06Rik, Hspa1b, Hspa1a, Cox6a2, Ibtk, Banf1, Slc35b2, Golt1b, Lrp8, and Pttg1) with opposite expression trends and a regulator gene Cerkl with the similar expression trend in the Control and BPA groups were identified. Hif1α might be an important molecular target for pancreatic cancer caused by BPA exposure, and pregnancy is a critical window of susceptibility to BPA exposure.

G protein-coupled estrogen receptor activation by bisphenol-A disrupts lipid metabolism and induces ferroptosis in the liver

As a metabolic disruptor, bisphenol A (BPA) has been widely reported to disrupt lipid balance. Moreover, BPA has gained significant attention due to its estrogenic activity. While both ferroptosis and the G-protein-coupled estrogen receptor (GPER) have been implicated in lipid metabolism, their link to BPA-induced lipid accumulation remains unclear. In this study, chickens were randomly assigned to three groups and housed them for 4 weeks: a control group (0 μg/L BPA), a low dose group (50 μg/L BPA) and a high dose group (5000 μg/L BPA) to investigate the underlying mechanism of BPA-induced hepatotoxicity. Our results showed that BPA exposure significantly increased the contents of TG, TC, and LDL-C while decreasing HDL-C levels. We also found that BPA treatment altered the levels of genes involved in fatty acid β-oxidation (ampkα, cpt-1, and ppaα), synthesis (acc, fas, scd-1, and srebp-1) and absorption (lpl and cd36). Moreover, the results showed that the BPA group had higher levels of IL-1β, IL-18 and TNF-α. These results indicated that BPA exposure disrupted lipid metabolism and induced inflammation in the liver. We also demonstrated that BPA caused hepatic ferroptosis by raising iron content and the expression of genes related to lipid peroxidation (lpcat3, acsl4 and alox15), while reducing the expression of antioxidant system-associated genes (gpx4, slc7a11 and slc3a2). Importantly, BPA remarkably activated GPER expression in the liver. Interestingly, inhibition of GPER remarkably ameliorated BPA-induced lipid metabolism disorder, inflammatory response, and ferroptosis, indicating the crucial role of GPER in BPA-induced liver abnormalities. These findings highlight the link between GPER and ferroptosis in BPA-induced hepatotoxicity, providing new insights into the potential hazard of BPA.

The role of PERK-eIF2α-ATF4-CHOP pathway in the apoptosis of TM4 cells induced by bisphenol A

To investigate the effects of bisphenol A(BPA) on the proliferation and apoptosis of mouse testicular sertoli cells(TM4 cells) and the role of PERK-eIF2α-ATF4-CHOP pathway. TM4 cells were treated with different concentrations of BPA(0, 25, 50, 100 μmol/L) and 100 μmol/L BPA combined with protein kinase R-like ER kinase(PERK) inhibitor GSK2656157 for 24 h, and the apoptosis of TM4 cells was observed by TUNEL staining. The expression levels of Bax, Bcl-2, cleaved Caspase-3, GRP78 and PERK-eIF2α-ATF4-CHOP pathway-related proteins were detected by Western blot. The apoptosis rate of TM4 cells in 25, 50 and 100 μmol/L BPA exposed groups was increased to 3.31%±0.34%, 7.51%±1.10% and 14.58%±0.91%, respectively, which was significantly higher than that in control group(0.73%±0.03%, P&lt;0.05). Compared with the control group(1.00), cleaved Caspase-3 protein expression of TM4 cells in the 25, 50 and 100 μmol/L BPA exposed groups increased to 1.49±0.11, 1.59±0.12, 2.42±0.24, respectively; the ratio of Bax/Bcl-2 increased to 2.06±0.19, 3.94±0.034, 6.14±0.71, respectively; the protein expression of GRP78 increased to 1.29±0.06, 1.39±0.06, 1.92±0.17, respectively; the expression of p-PERK protein was increased to 1.64±0.03, 2.52±0.09, 2.80±0.11, respectively; the expression of p-eIF2α protein was increased to 1.79±0.05, 2.48±0.10, 4.77±0.32, respectively; ATF4 protein expression was increased to 2.51±0.03, 3.24±0.14 and 7.45±0.51, respectively; CHOP protein expression was increased to 1.44±0.01, 3.20±0.11 and 3.80±0.11, respectively, and all the differences were statistically significant(P&lt;0.05). Compared to 100 μmol/L BPA group, the expression level of p-PERK, p-eIF2α, ATF4, CHOP, cleaved Caspase-3 protein and the ratio of Bax/Bcl-2 in 100 μmol/L BPA+10 μmol/L GSK2656157 group were decreased to 2.17±0.11, 1.81±0.13, 1.71±0.23, 2.18±0.22, 1.43±0.03, 2.22±0.13, respectively; the apoptosis rate of TM4 cells was also decreased to 7.28%±0.47%, all the differences were statistically significant(P&lt;0.05). BPA can induce apoptosis of TM4 cells by activating endoplasmic reticulum stress and regulating PERK-eIF2α-ATF4-CHOP pathway.

Hepatoprotective effect of Artemisia Argyi essential oil on bisphenol A-induced hepatotoxicity via inhibition of ferroptosis in mice.

The environmental pollutant bisphenol A (BPA), used in the manufacture of plastic packaging materials for various diets, is widely distributed in the environment and causes severe hepatotoxicity by inducing oxidative stress. Artemisia argyi essential oil (AAEO), a volatile oil component isolated from Artemisia argyi H.Lév. & Vaniot, has pharmacological effects, especially for hepatoprotective actions. However, the potential effect of AAEO in BPA induced hepatotoxicity has not been characterized. First, we analyzed the chemical composition in AAEO by gas chromatography-mass spectrometry. Herein, we investigated the effect of AAEO on hepatic metabolic changes in mice exposed to BPA. Results showed that compared with the BPA group, AAEO could reduce the level of liver function enzymes in BPA mice serum, and ameliorate hepatic lesions and fibrosis. Additionally, 20 differential metabolites screened by metabolomics were mainly involved in the reprogramming of glutathione metabolism, purine metabolism, and polyunsaturated fatty acid synthesis. Moreover, AAEO could reduce hepatic ferroptosis induced by BPA, as demonstrated by reducing xanthine oxidase activity, up-regulating the activities of glutathione peroxidase 4 (GPX4), superoxide dismutase, and catalase and the expression of SLC7A11 to promote the glutathione synthetic, while inhibiting transferrin receptor 1 (TFR1) expression to reduce the accumulation of Fe2+ in cells. Therefore, our study identified AAEO as a hepatic protectant against BPA-induced hepatotoxicity by reversing the occurrence of ferroptosis.

Cuscuta chinensis flavonoids reducing oxidative stress of the improve sperm damage in bisphenol A exposed mice offspring

Bisphenol A (BPA) is a common environmental endocrine disruptor, and overexposure is a threat to male reproduction. Although studies have confirmed that BPA exposure causes a decrease in sperm quality in offspring, the dosage used, and the underlying mechanism is not clear. The purpose of this study is to investigate whether Cuscuta chinensis flavonoids (CCFs) can antagonize or alleviate BPA-induced reproductive injury by analyzing the processes associated with BPA's impairment of sperm quality. BPA and 40 mg/kg bw/day of CCFs were administered to the dams at gestation day (GD) 0.5–17.5. Testicles and serum of male mice are collected on postnatal day 56 (PND56), and spermatozoa are collected to detect relevant indicators. Our results showed that compared with the BPA group, CCFs could significantly increase the serum contents of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) in males at PND 56, as well as the transcription levels of estrogen receptor alpha (ERα), steroidogenic acute regulatory protein (StAR) and Cytochrome P450 family 11, subfamily A, and member 1 (CYP11A1). CCFs also significantly inhibit the production of reactive oxygen species (ROS), reduce oxidative stress, increase mitochondrial membrane potential, and reduce sperm apoptosis. It also has a certain regulatory effect on sperm telomere length and mitochondrial DNA copy number. These results suggest that CCFs can increase reproductive hormone and receptor levels in adult males by regulating the expression of oxidative stress correlated factors, and ultimately mitigate the negative effects of BPA on sperm quality in male mice.

Metabolomic analysis of the inhibitory effect of phthalates and bisphenol A on the antioxidant activity of vitamin D in human samples using liquid chromatography–mass spectrometry

Vitamin D is important because it has roles in maintaining musculoskeletal health, redox homeostasis, and the immune system; however, it is commonly dysregulated by endocrine disrupting chemicals, particularly phthalates and bisphenol A (BPA). Continuous exposure to phthalates and BPA may alter the endogenous metabolite profiles associated with vitamin D activity, although the specific metabolites are yet to be identified. In this study, we identified the endogenous metabolites altered by phthalates and BPA exposure through untargeted metabolic profiling and investigated the role of these metabolites in vitamin D activity. Plasma metabolic profiling using liquid chromatography-mass spectrometry was performed in two groups: severe 25-hydroxyvitamin D (25(OH)D) deficiency and high exposure to phthalates and BPA (Group A) and 25(OH)D deficiency and low exposure to phthalates and BPA (Group B). Multivariate analysis revealed a distinct separation between the two groups. A total of six metabolites were annotated, of which levels of two were significantly different between the two groups: platelet-activating factor (PAF) C16 or lysophosphatidylcholine (lysoPC) 18:0, and 11Z-eicosenamide.Plasma levels of PAF C16 or lysoPC 18:0 were increased in Group A and exhibited an area under the curve of 0.769 with an accuracy of 74.4% in a receiver operating characteristic curve analysis. These metabolites are generated as byproducts of lipid peroxidation, which supports the fact that phthalates and BPA induce oxidative stress in cells. Furthermore, PAF C16 and lysoPC 18:0 may be involved in the network that interferes with the antioxidant activity of vitamin D upon exposure to phthalates and BPA. This study results provide useful information on how the activity of vitamin D on the antioxidant system is inhibited when exposure to phthalates and BPA.

Забруднювач довкілля бісфенол А порушує програмування статевої поведінки у жіночого потомства щурів

Bisphenol A (BPA) is a common environmental pollutant and, due to its estrogenic properties, can cause disorders of the reproductive and other physiological systems of the body, especially in males. It is known that in male rats it disrupts the sexual differentiation of the brain (SDB) of the fetus in utero. Studies of the effects of perinatal exposure of fetuses and newborn females through the mother’s body under the conditions of long-term administration of BPA during pregnancy and lactation did not reveal significant changes in SDB. Identification of long-term endocrine, neuromorphological, and behavioral consequences of exposure of female rat fetuses to a low dose of BPA administered to mothers during the last week of pregnancy, which corresponds to the temporal period of SDB, was the aim of this study. Rats were orally administered BPA suspended in Dorfman gel at a daily dose of 25 μg/kg b.w., which is 200 times less than the NOAEL (no observed adverse effect level) for rats, via a gavage, or, as a positive control, estradiol diacetate (E2D) subcutaneously at a dose of 10 μg/kg b.w., during 15-21 days of pregnancy. Control animals received gel without BPA. The levels of estradiol, testosterone, and corticosterone in blood plasma, the response of the hypothalamic-pituitary-adrenal (HPA) axis to acute immobilization stress, sexual behavior, and the histological structure and karyometric parameters of neurocytes of the medial-preoptic nuclei (MPN) of the hypothalamus were studied in adult female offspring. Prenatal exposure to BPA or E2D decreased the concentration of estradiol in the blood plasma, while the levels of testosterone and corticosterone remained normal. In the females of the BPA and E2D groups, a masculinization of sexual behavior (mounting to a receptive female, approaching her, etc.) was observed, which, according to the number of lordosis reactions in the presence of a sexually experienced male, not accompanied by her defeminization. Changes in the morphology of the MPN, which belongs to the sex-dimorphic area of the brain, conformed to the masculinization of female sexual behavior due to prenatal exposure to a low dose of BPA. Karyometry of neurocytes of the hypothalamic MPN of rats revealed no difference between the control and the BPA group. The response of the HPA axis to immobilization stress did not change in both experimental groups. It is found for the first time that maternal exposure of in utero female rat fetuses to an ultra-low relative to the NOAEL dose of BPA during the last gestational week, which corresponds to the critical period of SDB impairs programming of sexual behavior in the direction of its masculinization and causes hypoestrogenemia at adulthood. Disorders of sexual behavior conformed to morphological changes of the hypothalamic MPN. The unidirectionality of functional disorders induced by prenatal exposure to BPA and the reference estrogenic drug E2D indicates that they are caused by the estrogenic properties of both substances.

Bisphenol A exposure induces testicular oxidative damage via FTO/m6A/Nrf2 axis during postnatal development in mice.

Bisphenol A (BPA), a commonly used plasticizer in the production of polycarbonate plastics and epoxy resins, has been shown to induce male reproductive toxicity. However, the effects of BPA exposure on early testicular development have not been thoroughly studied, and the underlying mechanism is yet to be elucidated. In the current study, neonatal male mice were exposed to BPA at 0, 0.1, and 5mg/kg, respectively, by daily subcutaneous injection during postnatal day (PND) 1-35 to explore its effects on testicular development at PND 36 (the end of the first round of spermatogenesis). Morphological analyses showed that BPA exposure significantly induced apoptosis of testicular cells (p < 0.01 and p < 0.001) and reduced the thickness of seminiferous epithelium (p < 0.01). In addition, BPA exposure significantly decreased the total antioxidant capacity of testes and levels of transcription factor Nrf2 as well as its downstream antioxidant molecules of NQO1 and GPx-1 (p < 0.05 and p < 0.01). Furthermore, global m6A modifications of mRNAs were upregulated accompanied by declined m6A demethylase (FTO) in the testes of BPA groups (p < 0.05 and p < 0.01). MeRIP-quantitative real-time polymerase chain reaction (qPCR) demonstrated that BPA exposure markedly increased the m6A modification of Nrf2 mRNA (p < 0.05 and p < 0.01). These findings suggest that upregulation of m6A induced by inhibited FTO may be involved in BPA-induced testicular oxidative stress and developmental injury during postnatal development, which provides a new idea to reveal the mechanism underlying BPA interfering with testicular development.

Sex-specific associations between urinary bisphenols concentrations during pregnancy and problematic child behaviors at age 2 years

Effects of prenatal bisphenol A (BPA) exposure on child behavior are mixed with some reports suggesting increased problematic behaviors in girls (e.g., aggression and emotional reactivity) and in boys (i.e., externalizing behaviors), while other reports suggest decreased problematic behaviors in girls. Little is known about the potential impact of pregnancy bisphenol S (BPS) exposure on child behavior. In a prospective cohort study (n = 68), five maternal spot urine samples collected across pregnancy were pooled and analyzed for BPA and BPS. Child behavior at 2 years was assessed using the Child Behavior Checklist (CBCL). Linear regression models were used to assess associations between bisphenols concentrations and both composite and syndrome CBCL scales. Exposure x child sex interactions were included in addition to their main effects and sex-stratified analyses were conducted. Models were adjusted for maternal age, number of siblings, and child age at CBCL intake. Mean maternal age was 29.7 years. Most women were White (88%), had an annual household income ≥$50,000 (66%), and at least a college degree (81%). Median concentrations were 1.3 ng/mL (range 0.4–7.2) for BPA and 0.3 ng/mL (range 0.1–3.5) for BPS. Sex modified the relationship between BPA and scores on several syndrome scales—anxious-depressed, aggressive, and sleep problems—where the association was consistently inverse in males in lower BPA concentrations, and positive (more reported behavior problems) among girls in the higher BPA group. Higher BPS was associated with more problematic internalizing behaviors among girls but not boys, and sex modified the relationship between BPS and emotionally reactive behaviors (Pinteraction = 0.128), with sex-specific estimates revealing more emotionally reactive behaviors among girls (expβ = 3.92 95% CI 1.16, 13.27; P = 0.028) but not boys. Findings were mixed overall, but one notable finding was that BPS, a replacement for BPA, was associated with increased problematic behaviors. There is a need for replication of findings due to our small sample size.

Restoration of hepatorenal dysfunction and injury by zinc and folic acid combination in bisphenol A-intoxicated mice

Bisphenol-A (BPA) is a potentially hazardous substance and is extensively used in manufacturing industries as a plasticizing agent. The current research intended to determine the revival actions of zinc (Zn) and folic acid (FA) on hematological parameters and hepatorenal function in BPA-exposed male albino mice. A total of 75 adult male mice, aged 25 to 28 days, were split into five groups. Group A (the control group) received a normal diet, while a daily dosage of 50 mg BPA/kg body weight (BW) in the diet was provided to groups B–E. Groups C, D, and E received daily supplements of 10 mg Zn/kg BW, 3 mg FA/kg BW, or both in the feed. After 12 weeks of treatment, serum was prepared by collecting blood, and the kidney and liver were taken for a histotexture study. The results demonstrate that hematological values dropped significantly (p&lt; 0.05) in the BPA-treated group and increased following Zn and FA supplementations, while no significant alterations in erythrocyte indices were observed among control and treated groups. The BPA group used to have significantly (p&lt; 0.05) higher liver and kidney biomarkers levels, which were restored by Zn and FA. The effects of BPA administration included severe hepatocyte degeneration and necrosis, as well as renal tubule epithelium loss, all of which were improved by Zn and FA. Hence, the findings suggest Zn and FA could be potential preventative agents against BPA-induced toxicity.

Assessment of β-cyclodextrin-immobilizing hydrolyzed polyacrylonitrile membrane for enhanced remediation of bisphenol A and tetracyclines: Adsorption and antibacterial studies

A citric acid-crosslinked β-cyclodextrin modifying hydrolyzed polyacrylonitrile membrane (β-CD-HPAN) was designed for bisphenol A (BPA), tetracycline (TC), and oxytetracycline (OTC) uptake. β-CD-HPAN was successfully prepared with several characterizations and optimized synthesis conditions. In batch mode, there was a good removal capacity toward BPA in a broad pH range, the uptake of TC and OTC (TCs) possessed a relatively high adsorption effect at pH of 3.0–4.0. The addition of salinity had a negative result on adsorption. The isotherm behaviors exhibited a monolayer equilibrium removal capacity (qe) of 45.3 mg/g for BPA, with heterogeneous qe of 124 mg/g and 98.4 mg/g for TC and OTC, respectively. These processes were accorded with Koble-Corrigan isotherm model, and the kinetic behaviors followed Elovich equation. The binary experiment elucidated that BPA and TC/OTC removal onto β-CD-HPAN was independent from each other. β-CD-HPAN also elucidated good regeneration performances. Adsorption mechanisms were proposed that β-CD cavities on β-CD-HPAN mainly contributed to entrap molecules of non-polar BPA, carboxyl and hydroxyl groups provided binding sites for polar TCs. The membrane owned antibacterial capacity against gram-positive S. aureus. Overall, β-CD-HPAN membrane has great potentials in wastewater purification to adsorb BPA and TCs due to its green synthetic procedure, easy separation, bifunctional groups, and low cost.

Potential Effects of Bisphenol A on the Heart and Coronary Artery of Adult Male Rats and the Possible Role of L-Carnitine.

Bisphenol A (BPA) is an environmental toxin utilized for the production of polycarbonate plastics and epoxy resins. Due to BPA's extensive production and environmental contamination, human exposure is unavoidable. The effects of low-dose of BPA on various body tissues and organs remain controversial. Our study investigated the potential of BPA to induce biochemical, histopathological, and immunohistochemical changes in the coronary artery and myocardium and the potential protective role of L-carnitine (LC). 24 adult Wistar albino male rats were divided equally into a control group, a BPA-treated group (40 mg/kg/d, by gavage for 4 weeks), and a BPA plus LC-treated group (received 40 mg/kg/d of BPA and 300 mg/kg/d of LC, by gavage for 4 weeks). BPA-exposed rats demonstrated structural anomalies in the coronary artery tissue including vacuolation of cells in the media and detachment of the endothelium of the intima. Congestion of blood vessels and infiltration by polynuclear cells were observed in the myocardium. There was an enhanced collagen deposition in both tissues indicating fibrosis. Immunohistochemical changes included enhanced eNOS and caspase-3 expression in the coronary artery and myocardium indicating vascular disease and apoptosis, respectively. Oxidative damage was evident in the coronary artery and the myocardium of BPA-treated rats, which was indicated by the reduced level of glutathione (GSH) and elevated malondydehyde (MDA) levels. The coadministration of LC significantly improved BPA-induced structural alterations and oxidative stress. In conclusion, BPA could potentially cause pathologic changes and oxidative damage in the coronary artery and myocardium, which could be improved by LC coadministration.

Expression Profile of Hydroxysteroid Dehydrogenase-like 2 in Polychaete Perinereis aibuhitensis in Response to BPA.

Hydroxysteroid dehydrogenases (HSDs) play an important role in the metabolism of steroids and xenobiotics. However, the function of HSDs in invertebrates is unclear. In this study, we cloned the hydroxysteroid dehydrogenase-like 2 (HSDL2) gene in Perinereis aibuhitensis, which is 1652 bp in length, encoding 400 amino acids. This sequence contains conserved short-chain dehydrogenase and sterol carrier protein-2 domain, and the alignment analysis showed its close relationship with other invertebrate HSDL2. Further, the tissue distribution analysis of the HSDL2 gene showed it is expressed strongly in the intestine. The expression level of HSDL2 after inducement with bisphenol A (BPA) was also detected both at transcriptional and translational levels. The results inferred that BPA exposure can induce HSDL2 expression, and the inductive effect was obvious in the high-concentration BPA group (100 μg/L). In summary, our results showed the detoxification function of HSDL2 in polychaetes.

Evaluation the Effect of Crocin on Bisphenol A-Induced Memory Impairment in Rats: Role of ERK, CaMKII, and CREB Proteins in Hippocampus

Introduction: Bisphenol A (BPA) is a toxic chemical that is used as a monomer in the production of plastic products. The BPA has an endocrine-disrupting effect and ‎induces damage to the nervous system. Crocin, an active ingredient of Crocus sativus L. has ‎neuroprotective effects. Therefore, this study aimed to evaluate crocin’s effects on BPA-induced ‎memory impairment in rats and the levels of Extracellular Signal-Regulated Kinases (ERK), Ca2+/Calmodulin-Dependent Protein Kinase-II (CaMKII), and Cyclic AMP-Response Element-Binding Protein (CREB) proteins in the hippocampus. Method: Bisphenol A (100 mg/kg, gavage) and crocin (10, 20, and 40 mg/kg, IP) were administered to adult male rats for 28 days. Memory and learning functions were evaluated by the Morris water maze, and the level of proteins was determined using the Western blot method. Results: Administration of the BPA (100 mg/kg) significantly induced memory impairment and reduced the levels of ERK, p.ERK, CaMKII, and p.CREB proteins in the BPA group, compared to the control group. On the other hand, crocin (20 mg/kg) markedly improved learning and memory impairment and increased the levels of ERK, p.ERK, and CaMKII proteins in the hippocampus, compared to the BPA (100 mg/kg) group. Conclusion: Administration of crocin (20 mg/kg) improves memory and learning defects induced by BPA (100 mg/kg). The enhancement of the ‎p.ERK, ERK, and p. CaMKII protein levels in the hippocampus has an important role in crocin protective effects

Genome-wide distribution of histone trimethylation reveals a global impact of bisphenol A on telomeric binding proteins and histone acetyltransferase factors: a pilot study with human and in vitro data

ObjectiveTo assess the genetic and epigenetic effects promoted by Bisphenol A (BPA) exposure in adolescent males from the Spanish INMA-Granada birth cohort, and in human cells.MethodsDNA methylation was analysed using MEDIP. Repeat number variation in genomic DNA was evaluated, along with the analysis of H3K4me3 by using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Analyses were performed with material extracted from whole blood of the adolescents, complemented by in vitro assessments of human (HeLa) cells exposed to 10 nM BPA, specifically, immunofluorescence evaluation of protein levels, gene expression analysis and ChIP‒qPCR analysis.ResultsAdolescents in the high urinary BPA levels group presented a higher level of Satellite A (SATA) repetitive region copy numbers compared to those in the low BPA group and a tendency towards increase in telomere length. We also observed decreased DNA methylation at the promoters of the imprinted genes H19, KCNQ1, and IGF2; at LINE1 retroelements; and at the ARID2, EGFR and ESRRA and TERT genes. Genome-wide sequencing revealed increased H3K4me3 occupancy at the promoters of genes encoding histone acetyltransferases, telomeric DNA binding factors and DNA repair genes. Results were supported in HeLa cells exposed to 10 nM BPA in vitro. In accordance with the data obtained in blood samples, we observed higher H3K4me3 occupancy and lower DNA methylation at some specific targets in HeLa cells. In exposed cells, changes in the expression of genes encoding DNA repair factors (ATM, ARID2, TRP53) were observed, and increased expression of several genes encoding telomeric DNA binding factors (SMG7, TERT, TEN1, UPF1, ZBTB48) were also found. Furthermore, an increase in ESR1/ERa was observed in the nuclei of HeLa cells along with increased binding of ESR1 to KAT5, KMT2E and TERF2IP promoters and decreased ESR1 binding at the RARA promoter. The DNA damage marker p53/TP53 was also increased.ConclusionIn this pilot study, genome-wide analysis of histone trimethylation in adolescent males exposed to BPA revealed a global impact on the expression of genes encoding telomeric binding proteins and histone acetyltransferase factors with similar results in HeLa cells. Nevertheless, larger studies should confirm our findings.

Determination of Metabolomics Profiling in BPA-Induced Impaired Metabolism.

Exposure to bisphenol A (BPA) is unavoidable and it has far-reaching negative effects on living systems. This study aimed to explore the toxic effects of BPA in an experimental animal model through a metabolomics approach that is useful in measuring small molecule perturbations. Beside this, we also examined the ameliorative effects of resveratrol (RSV) against BPA-induced disturbances in experimental mice. This study was conducted for 28 days, and the results showed that BPA indeed induced an impairment in amino acid metabolism, taking place in the mitochondria by significantly (p &lt; 0.05) decreasing the levels of certain amino acids, i.e., taurine, threonine, asparagine, leucine, norleucine, and glutamic acid in the mice plasma. However, the administration of RSV did prove effective against the BPA-induced intoxication and significantly (p &lt; 0.05) restored the level of free amino acids. Lipid metabolites, L-carnitine, sphinganine, phytosphingosine, and lysophosphatidylcholine were also determined in the mice serum. A significant (p &lt; 0.05) decline in glutathione peroxidase (GPx), superoxide dismutase (SOD,) glutathione, and catalase levels and an elevation in malondialdehyde level in the BPA group confirmed the generation of oxidative stress and lipid peroxidation in experimental mice exposed to BPA. The expression of Carnitine palmitoyltransferase I (CPT-I), carnitine palmitoyltransferase II (CPT-II), lecithin-cholesterol acyltransferase (LCAT), carnitine O-octanoyltransferase (CROT), carnitine-acylcarnitine translocase (CACT), and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) genes was significantly upregulated in the liver tissue homogenates of experimental mice exposed to BPA, although RSV regulated the expression of these genes when compared with BPA treated experimental mice. CPT-I, CPT-II, and CACT genes are located in the mitochondria and are involved in the metabolism and transportation of carnitine. Hence, this study confirms that BPA exposure induced oxidative stress, upregulated gene expression, and impaired lipid and amino acid metabolism in experimental mice.

Bisphenol A exacerbates selenium deficiency-induced pyroptosis via the NF-κB/NLRP3/Caspase-1 pathway in chicken trachea

Selenium deficiency can lead to multiple tissue and organ damage in the body and could coexist with chronic toxic exposures. Contamination from Bisphenol A (BPA) exposure can induce the occurrence of various injuries including pyroptosis. However, it is not clear whether selenium deficiency and BPA exposure affect tracheal tissue pyroptosis in chickens. To investigate whether selenium deficiency and BPA exposure induce chicken tracheal tissue pyroptosis via the NF-κB/NLRP3/Caspase-1 pathway and the effect of their combined exposure on tissue injury, we developed a model of relevant chicken tracheal injury. Sixty broilers were divided into four groups: the control group (C group), selenium-deficient group (SeD group), BPA-exposed group (BPA group) and combined exposure group (SeD + BPA group). The study examined the expression indicators of markers of pyroptosis (NLRP3&GSDMD), NF-κB pathway-related inflammatory factors (NF-κB, iNOS, TNF-α, COX-2), pyroptosis-related factors (ASC, Caspase-1, IL-1β, IL-18), and some heat shock proteins and interleukins (HSP60, HSP90, IL-6, IL-17) in the samples. The results showed that the expression of the above indicators was significantly upregulated in the different treatment groups (P < 0.05). In addition, the expression levels of the above related indicators were more significantly up-regulated in the combined selenium-deficient and BPA-exposed group compared to the group in which they were individually exposed. It was concluded that selenium deficiency and BPA exposure induced tracheal tissue pyroptosis in chickens through NF-κB/NLRP3/Caspase-1 pathway, and BPA exposure exacerbated selenium deficiency-induced tracheal pyroptosis. The present study provides new ideas into studies related to the co-exposure of organismal micronutrient deficiency and chronic toxicants.