High Doses Of Bisphenol A Research Articles

The Possible Protective Effect of Taurine on Bisphenol Induced Structural Changes on the Cerebral Cortex of Rats: Histological and Immunohistochemical Study.

Bisphenol A (BPA) is a chemical compound that has been used in many industries, such as paints and dental sealants. Taurine is a semi-essential amino acid with antioxidant, anti-inflammatory, and anti-apoptotic actions. This study aimed to evaluate the possible protective effect of taurine on BPA-induced structural changes in the cerebral cortex of rats using histological and immunohistochemical methods. 35 Wistar rats (180-200 gm) were divided into control: 10 rats; Group I: 5 rats received corn oil (0.5 mL/day); Group II (Bisphenol low dose; BPAL): 5 rats received a low dose of BPA (25 mg/kg/three times/week); Group III (Bisphenol high dose; BPAH): 5 rats received a high dose of BPA (100 mg/kg/three times/week; Group IV: (BPAL + taurine): 5 rats received taurine 100 mg/kg/day and BPAL (25 mg/kg/three times/week); Group V: (BPAH + taurine): 5 rats received taurine 100 mg/kg/day and BPH (100 mg/kg/ three times/week). BPAL& BPAH groups showed significant dose-dependent histological changes of the neuropil, pyramidal, and neuroglial cells at H&E stained sections, significantly increased GFAP, caspase- 3 immunohistochemical reaction with cells positive for Ki67 with many mitotic figures. BPAL + taurine and BPAH + taurine groups showed amelioration of the previously mentioned results. Taurine ameliorated the structural changes induced by BPA in the cerebral cortex of rats.

Use of Mesenchymal Stem Cells in Experimental Ovarian Damage.

Bisphenol-A (BPA) has a well-proven deleterious effect on the hypothalamicpituitary- gonadal axis. The current study investigated the therapeutic potentials of mesenchymal stem cells (MSCs) in a murine model of BPA-induced ovarian damage. Fifty adult female rats were divided into: Group 1; control group, Group IIa, IIb: rats were given oral gavage of BPA (25 and 50 mg/Kg body weight respectively) on a daily basis for 15 days, and Group IIIa, IIIb; rats were intravenously treated with of MSCs (106 cells) after receiving the last dose of BPA as in group II. Plasma and ovarian tissue levels of Malondialdehyde (MDA) and gonadal axis hormones were assessed. Apoptosis was evaluated by TUNNEL assay and by apoptosis markers (FAS, FASL, Caspase 3, SLTM). A histological examination of ovarian tissue was also conducted. BPA resulted in a significant elevation in plasma levels of LH, FSH, and ovarian tissue levels of MDA and a significant decrease in estradiol and progesterone. All genetic and protein markers of apoptosis were elevated in BPA treated group with decreased oestrogen receptor expression in the ovarian tissue. Increased apoptotic cells were confirmed by TUNEL assay. A high dose of BPA was able to increase the number of atretic follicles in the ovarian tissue whereas the numbers of primordial, primary, secondary and Graafian follicles were decreased. All the laboratory and histological abnormalities were ameliorated by treatment with MSCs. The antioxidant and anti-apoptotic effects of MSCs could possibly explain the ability of this therapeutic modality to ameliorate BPA-induced-ovarian damage.

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 (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.

The Protective Effects of Syringic Acid on Bisphenol A-Induced Neurotoxicity Possibly Through AMPK/PGC-1α/Fndc5 and CREB/BDNF Signaling Pathways.

Bisphenol A (BPA), an endocrine disruptor, is commonly used to produce epoxy resins and polycarbonate plastics. Continuous exposure to BPA may contribute to the development of diseases in humans and seriously affect their health. Previous research suggests a significant relationship between the increased incidence of neurological diseases and the level of BPA in the living environment. Syringic acid (SA), a natural derivative of gallic acid, has recently considered much attention due to neuromodulator activity and its anti-oxidant, anti-apoptotic, and anti-inflammatory effects. Therefore, in this study, we aimed to investigate the effects of SA on oxidative stress, apoptosis, memory and locomotor disorders, and mitochondrial function, and to identify the mechanisms related to Alzheimer's disease (AD) in the brain of rats receiving high doses of BPA. For this purpose, male Wistar rats received BPA (50, 100, and 200mg/kg) and SA (50mg/kg) for 21days. The results showed that BPA exposure significantly altered the rats' neurobehavioral responses. Additionally, BPA, by increasing the level of ROS, and MDA level, increased the level of oxidative stress while reducing the level of antioxidant enzymes, such as SOD, CAT, GPx, and mitochondrial GSH. The administration of BPA at 200mg/kg significantly decreased the expression of ERRα, TFAM, irisin, PGC-1α, Bcl-2, and FNDC5, while it increased the expression of TrkB, cytochrome C, caspase 3, and Bax. Moreover, the Western blotting results showed that BPA increased the levels of P-AMPK, GSK3b, p-tau, and Aβ, while it decreased the levels of PKA, P-PKA, Akt, BDNF, CREB, P-CREB, and PI3K. Meanwhile, SA at 50mg/kg reversed the behavioral, biochemical, and molecular changes induced by high doses of BPA. Overall, BPA could lead to the development of AD by affecting the mitochondria-dependent apoptosis pathway, as well as AMPK/PGC-1α/FNDC5 and CREB/BDNF/TrkB signaling pathways, and finally, by increasing the expression of tau and Aβ proteins. In conclusion, SA, as an antioxidant, significantly reduced the toxicity of BPA.

Impact of bisphenol A on cell viability and inflammatory cytokine production in human cervical epithelial cells.

An intact cervix is a barrier that prevents pathogenic bacteria from invading the uterine and amniotic cavity during pregnancy. Its disruption is associated with ascending infection and adverse pregnancy outcomes. This study analyzed the effects of bisphenol A (BPA), a chemical used in plastics manufacturing, on cell death and inflammation in cervical epithelial cells. Ectocervical epithelial (ecto) and endocervical epithelial (endo) cells were treated with 100ng/mL and 300ng/mL of BPA for 48h. The cells were subjected to flow cytometry using annexin V and propidium iodide to determine apoptosis and necrosis, cell cycle analysis, and ELISA to determine the levels of inflammatory cytokines (IL-6, IL-8, and IL-10). Low-dose and high-dose BPA significantly increased the live ecto cell population dose-dependently. BPA did not have any noticeable effect on cell cycle progression in either cell type. BPA treatment also decreased the apoptotic ecto and endo cell population dose-dependently. Lastly, high dose BPA significantly increased IL-6 in ecto and endo cells. However, IL-8 and IL-10 were not affected by BPA treatments. Chemical exposure damage to the cervix can lead to adverse pregnancy outcomes. Our study showed that the BPA concentrations reported in pregnant subjects do not induce cervical cell toxicity . The decrease in apoptosis and increase in live cells may be a compensatory mechanism to preserve the integrity of the cervical epithelial layer.

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.

Developmental neurotoxic effects of bisphenol A and its derivatives in Drosophila melanogaster

As a result of the ban on bisphenol A (BPA), a hormone disruptor with developmental neurotoxicity, several BPA derivatives (BPs) have been widely used in industrial production. However, there are no effective methods for assessing the neurodevelopmental toxic effects of BPs. To address this, a Drosophila exposure model was established, and W1118 was reared in food containing these BPs. Results showed that each BPs displayed different semi-lethal doses ranging from 1.76 to 19.43 mM. Exposure to BPs delayed larval development and affected axonal growth, resulting in the abnormal crossing of the midline of axons in the β lobules of mushroom bodies, but the damage caused by BPE and BPF was relatively minor. BPC, BPAF, and BPAP have the most significant effects on locomotor behavior, whereas BPC exhibited the most affected social interactions. Furthermore, exposure to high-dose BPA, BPC, BPS, BPAF, and BPAP also significantly increased the expression of Drosophila estrogen-related receptors. These demonstrated that different kinds of BPs had different levels of neurodevelopmental toxicity, and the severity was BPZ > BPC and BPAF > BPB > BPS > BPAP ≈ BPAl ≈ BPF > BPE. Therefore, BPZ, BPC, BPS, BPAF, and BPAP should be evaluated as potential alternatives to BPA.

Effects of bisphenol A on antioxidation and nitrogen assimilation of maize seedlings roots

Bisphenol A (BPA) is becoming a potential environmental toxicity factor. However, BPA's effect and function mechanism on maize roots remain unknown. Here, we investigated characters of root growth of maize seedlings exposed to BPA for 8 d and without BPA for 3 d, and a series of indicators on reactive oxygen homeostasis and nitrogen assimilation were measured. High-dose BPA(15 and 50 mg·L−1) suppressed the root growth and caused increased contents of O2ˑ-, H2O2 and MDA in maize seedling roots. The disturbed ROS homeostasis resulted from the change of antioxidant enzymes, including the increase of APX, GPX, and CAT, and decrease of SOD and POD, and a decrease of antioxidant substance GSH. Meanwhile, High-dose BPA caused a decrease in the soluble protein content, nitrate reductase (NR), glutamate dehydrogenase (GDH), and glutamine oxoglutarate aminotransferase (GOGAT) under the BPA processing phase and recovery period. The low-dose BPA（1.5 and 5 mg·L−1）significantly promoted root growth of maize seedlings and maintained the ROS homeostasis through antioxidant enzyme APX and GPX eliminating redundant ROS. Our results showed that BPA could cause a dual effect on the root growth of maize seedlings, that is, promotion of low-dose and inhibition of high-dose, through ROS homeostasis and nitrogen assimilation in Zea mays.

Disturbance in Some Fertility Biomarkers Induced and Changes in Testis Architecture by Chronic Exposure to Various Dosages of Each of Nonylphenol or Bisphenol A and Their Mix.

Simple SummaryIn this study, 70 male albino rats were allocated to the control group (GI) and were given 1 mL of ethanol; G, II, and G III were treated with 100 mg/Kg of each of BPA and NP, G IV and G V were treated with 25 mg/Kg of each of BPA and NP, G VI was given a mixture of a high dose of BPA and NP, and G VII was given a mixture of a low dose of BPA and NP. A significant elevation in the TNF Alpha, TNF Beta, and Caspase 3 serum was recorded individually and in the groups treated with high doses. In conclusion, exposure to BPA and NP strongly impacts antioxidants, immune-inflammatory mediators, and testicular tissue architecture. Furthermore, the data from this investigation support the idea that exposure to BPA and NP in daily life has multiple damages.This investigation was conducted to demonstrate the potential impacts of different doses of Bisphenol A (BPA) or Nonylphenol (NP) and their mixtures on some biological activities in male albino rats. Seventy male albino rats were allocated to the control group (GI) and were given 1 mL of ethanol. G II and G III were given 100 mg/kg of each of BPA and NP, G IV and G V were given 25 mg/kg of each of BPA and NP, G VI was given a high dose of BPA and NP, and G VII was given a low dose of BPA and NP. All animals were treated orally for 60 days. Serum biomarkers of oxidative stress, antioxidants, immune-inflammatory mediators, and apoptotic markers were determined, as well as a histopathological examination of the testis at the end of the experimental period. The results obtained showed a pronounced increase in malondialdehyde (MDA), protein carbonyl (PC), and 4-hydroxynonenol (4-HNE), concomitant with a significant reduction in serum Superoxide dismutase (SOD), catalase enzyme (CAT), and total antioxidant capacity (TAC) in all treated groups. A significant elevation in TNF Alpha, TNF Beta, and Caspase 3 serum was recorded individually and in the groups treated with high doses. The disturbance is represented by histological damage in the testis in the germinal epithelium and a decrease in spermatozoa inside the lumen of seminiferous tubules. The effects on testis tissues were dose-dependent, pronounced in mixture doses, and remarkable in higher doses. In conclusion, exposure to BPA and NP strongly impacts antioxidants, immune-inflammatory mediators, and testis tissue architecture. Furthermore, the data from this investigation support the idea that exposure to BPA and NP in daily life has multiple damages.

Potential toxicity of bisphenol A to α-chymotrypsin and the corresponding mechanisms of their binding

Bisphenol A (BPA) is an endocrine disruptor widely existing in plastics and resins, which can accumulate in animals and human bodies, posing a potential threat to the physiological and biochemical reactions of human beings or other organisms. α-Chymotrypsin is a kind of proteolytic enzyme existing in humans and animals, which can cause diseases when its activity is excessive. However, there is a lack of research on the mechanism of endocrine disruptors affecting α-chymotrypsin activity. In this study, the interaction between BPA and α-chymotrypsin was proved via multiple spectroscopic approaches, enzyme activity change, isothermal titration calorimetry and molecular docking. Results showed that α-chymotrypsin’s polypeptide chains were unfolded, and protein skeletons were loosened with the exposure to BPA. α-Helix content increased and β-sheet content was decreased. The particle size of the BPA-α-chymotrypsin complex became smaller. Fluorescence sensitization may also be explained by a perturbation of the chromophore Trp 141. The thermodynamic parameters of the binding reaction were measured by isothermal titration calorimetry (ITC), which showed that there was hydrophobic interaction between BPA and α-chymotrypsin, which was consistent with the results of molecular docking. Moreover, BPA may stop near the active center of α-chymotrypsin and interact with the key residues His 57 and Ser 195. The above phenomenon explained the result that the activity of α-chymotrypsin increased to 139% when exposed to high dose BPA (40 μM). Taken together, the effects of BPA on the structure and function of α-chymotrypsin were clarified at the molecular level, which made up the gap in the mechanism of BPA on the proteolytic enzyme, and provided a reliable basis for disease avoidance and prevention.

Exposure to Bisphenol A Caused Hepatoxicity and Intestinal Flora Disorder in Rats.

Bisphenol A (BPA) is a globally utilized industrial chemical and is commonly used as a monomer of polycarbonate plastics and epoxy resins. Recent research reveals that BPA could cause potential adverse biological effects and liver dysfunction. However, the underlying mechanisms of BPA-induced hepatoxicity and gut dysbiosis remain unclear and deserve further study. In this study, male Sprague Dawley rats were exposed to different doses (0, 30, 90, and 270 mg/kg bw) of BPA by gavage for 30 days. The results showed that the high dose of BPA decreased superoxide dismutase (SOD), glutathione (GSH), and increased malondialdehyde (MDA) levels. Moreover, a high dose of BPA caused a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), while high-density lipoprotein cholesterol (HDL-C) was significantly decreased in BPA-treated rats. The gene expression of PGC-1α and Nrf1 were decreased in the liver of high doses of BPA-administrated rats, as well as the protein levels of SIRT1, PGC-1α, Nrf2, and TFAM. However, the protein expression of IL-1β was significantly increased in BPA-treated rats. In addition, BPA weakened the mitochondrial function of hepatocytes and promoted cell apoptosis in the liver by up-regulating the protein levels of Bax, cleaved-Caspase3, and cleaved-PARP1 while down-regulating the Bcl-2 in the liver. More importantly, a high dose of BPA caused a dramatic change in microbiota structure, as characterized at the genus level by increasing the ratio of Firmicutes to Bacteroidetes (F/B), and the relative abundance of Proteobacteria in feces, while decreasing the relative abundance of Prevotella_9 and Ruminococcaceae_UCG-014, which is positively correlated with the content of short-chain fatty acids (SCFAs). In summary, our data indicated that BPA exposure caused hepatoxicity through apoptosis and the SIRT1/PGC-1α pathway. BPA-induced intestinal flora and SCFA changes may be associated with hepatic damage. The results of this study provide a new sight for the understanding of BPA-induced hepatoxicity.

Phytoremediation potential, antioxidant response, photosynthetic behavior and rhizosphere bacterial community adaptation of tobacco (Nicotiana tabacum L.) in a bisphenol A-contaminated soil.

Bisphenol A (BPA) is an emerging organic pollutant, widely distributed and frequently detected in soil in recent years. BPA toxicity is a problem that needs to be solved in terms of both human health and agricultural production. Up to now, the toxic effect of BPA and its mechanism of action on plants, as well as the possibility of using plants to remediate BPA-contaminated soil, remain to be explored. In this study, six treatment groups were set up to evaluate the effects of different concentrations of BPA on the germination and growth of tobacco (Nicotiana tabacum L.) by medium experiments. Furthermore, the representative indexes of photosynthetic and antioxidant system were determined. Meanwhile, tobacco seedlings were cultivated in soil to further explore the effects of BPA on rhizosphere soil enzyme activity and bacterial community structure with or without 100mg/kg BPA exposure. The enhancement of BPA removal efficiency from soil by phytoremediation using tobacco plants would also be estimated. Our results showed that high doses of BPA in solid medium remarkably inhibited tobacco seedling growth, and its toxicology effect was positively correlated with BPA concentration, while lower BPA exposure (< 20mg/L) had little limitation on tobacco growth and induced hormesis effect, which was reflected mainly in the increase of root length. In pot experiments, the reducing of chlorophyll content (36.4%) and net photosynthetic rate (41.2%) meant the inhibition of tobacco photosynthetic process due to high concentration of BPA exposure (100mg/kg) in soil. The increase of H2O2 and O2- content suggested that BPA could destroy the balance of reactive oxygen species (ROS) in plants. However, tobacco plants still presented a high removal efficiency of BPA at the concentration of 100mg/kg in soil, which could reach to 80% within 30days. Furthermore, it was indicated that tobacco cultivation changed the structure of rhizosphere soil bacterial communities and the relative abundance of some valuable strains, including Proteobacteria, Acidobacteria and other strains, which might be participated in the BPA removal process. In addition, the tobacco-soil microbial system had the potential to reverse the negative effects caused by BPA through stimulating microorganism associated with soil nutrient cycling. In summary, tobacco is a competitive plant in phytoremediation of BPA-contaminated soil, though the growth of tobacco could be inhibited at high concentration of BPA. Moreover, tobacco might promote the removal efficiency of BPA by regulating the rhizosphere bacteria communities.

Effects of Bisphenol A on reproductive toxicity and gut microbiota dysbiosis in male rats

Bisphenol A (BPA) is an environmental endocrine disruptor. Recent studies have shown an association between decreased spermatogenesis and gut microbiota alteration. However, the potential associations and mechanisms of BPA exposure on spermatogenesis, hormone production, and gut microbiota remain unknown. This study aims to investigate BPA-induced male reproductive toxicity and the potential link with gut microbiota dysbiosis. Male Sprague Dawley rats were exposed to BPA at different doses by oral gavage for thirty consecutive days. The extent of testicular damage was evaluated by basic parameters of body weight and hematoxylin-eosin (H&E) staining. Next, we determined the mRNA levels and protein levels of apoptosis, histone-related factors, and mammalian target of rapamycin (mTOR) pathway in testes. Finally, 16 S rDNA sequencing was used to analyze gut microbiota composition after BPA exposure. BPA exposure damaged testicular histology, significantly decreased sperm count, and increased sperm abnormalities. In addition, BPA exposure caused oxidative stress and cell apoptosis in testes. The levels of histone (H2A, H3) were significantly increased, while ubiquitin histone H2A (ub-H2A) and ubiquitin histone H2B (ub-H2B) were markedly reduced. Furthermore, BPA activated the PI3K and AKT expression, but the protein expressions of mTOR and 4EBP1 in testes were inhibited significantly. Additionally, the relative abundance of class Gammaproteobacteria, and order Betaproteobacteriales was significantly higher when treated with a high dose of BPA compared to the control group, which was negatively correlated with testosterone level. This study highlights the relationship between BPA-induced reproductive toxicity and gut microbiota disorder and provides new insights into the prevention and treatment of BPA-induced reproductive damage.

Concentrations of bisphenol a (BPA) in fresh pork loin meat under standard stock-farming conditions and after oral exposure – A preliminary study.

Bisphenol A (BPA) is a substance commonly used in the production of plastics. It may be leached from plastics, penetrate to food and has multidirectional negative effects on living organisms. The aim of this study was to evaluate BPA levels in fresh pork meat collected immediately after the death of animals kept in standard stock-farming conditions, as well as from animals receiving various oral doses of BPA (0.05 mg/kg body weight (b.w.)/day and 0.5 mg/kg b. w./day).In animals kept in standard conditions, the average concentration of BPA in loin meat amounted to 37.03 ± 6.18 ng/g dry weight (d.w.). In animals receiving lower and higher doses of BPA, this value achieved 47.44 ± 4.39 ng/g d. w. and 214.30 ± 66.73 ng/g d. w, respectively. The results show that pork meat may be a source of BPA in human food and the presence of BPA in the meat may result from the exposure of animals over their lifetime. This observation shows that the elimination of BPA from the production of items used for animal husbandry and animal feed may reduce meat contaminated with this substance and, therefore, increase consumer safety.

Bisphenol A reveals its obesogenic effects through disrupting glucose tolerance, oxidant-antioxidant balance, and modulating inflammatory cytokines and fibroblast growth factor in zebrafish.

Obesogens affect lipid metabolism, and genetic or epigenetic factors may also contribute to the progression of obesity. Endocrine-disrupting chemicals (EDCs) are the most striking among obesogens. Bisphenol A (BPA) is an estrogenic EDC used in food containers, adhesives, dye powders, and dental fillers. We aimed to elucidate molecular mechanisms of BPA's obesogenic effects focusing on obesogenic pathways in the liver including fibroblast growth factor (FGF) and Dnmt3a which is its epigenetic regulator, oxidant-antioxidant status, and inflammatory cytokines. Zebrafish were divided into three groups as control, low-dose BPA (1μm BPA), and high-dose BPA groups (10μm BPA). At the end of 30days, oral glucose tolerance test (OGTT) was performed, fasting blood glucose levels were measured, and hepatopancreas tissues were taken. Malondialdehyde (MDA) levels, superoxide dismutase (SOD), glutathione S-transferase (GST), and nitric oxide (NO) activities were examined in the hepatopancreas. Inflammatory cytokines, lepa, fgf21, and dnmt3a expressions were determined by RT-PCR. BPA exposure increased the body weights, il1ß, tnfα, il6, lepa, fgf21, and dnmt3a expressions, impaired glucose tolerance, and oxidant-antioxidant status in a dose-dependent manner. Hepatocyte degeneration, lipid vacuolization, and vasocongestion were observed in both BPA-exposed groups. Our study suggests impaired glucose tolerance, oxidant-antioxidant balance, increased inflammatory response, fgf21 expression, and dnmt3a expressions as the possible mechanisms for the BPA-induced obesity model in zebrafish.

Comparative effects of genistein and bisphenol A on non-alcoholic fatty liver disease in laying hens

Bisphenol A (BPA) and genistein (GEN) are selective estrogen receptor modulators, which are involved in the occurrence and development of metabolic syndrome. However, their roles in non-alcoholic fatty liver disease (NAFLD) of laying hens have not been reported. Here, we investigated the effects of different concentrations of GEN and BPA on the NAFLD of laying hens. Results showed that GEN ameliorated the high-energy and low-protein diet (HELP)-induced NAFLD by improving pathological damage, hepatic steatosis, and insulin resistance and blocking the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-related factors. By contrast, high dose of BPA could aggravate these changes with serious symptom of NAFLD and suppress the level of ERα in the liver considerably, while GEN could reverse this phenomenon in a dose-dependent manner. In general, our research shows that the protective effect of GEN on NAFLD aims to improve the metabolic disorders and inflammation closely connected to ERα, while BPA can inhibit the expression of ERα and exacerbate the symptom of NAFLD. In conclusion, we elucidate the opposing effects of GEN and BPA in NAFLD of laying hens, thus providing a potential mechanism related to ERα and inflammation.

Alterations of Kiss 1 receptor, GnRH receptor and nuclear receptors of the hypothalamo-pituitary-ovarian axis following low dose bisphenol-A exposure in Wistar rats.

Bisphenol A is a chemical used primarily as a monomer in the production of polycarbonate plastics and epoxy resins. It is a synthetic chemical compound that is produced in billions of pounds annually, and tagged as an endocrine disruptor. Bisphenol A is a high production synthetic chemical compound that is used in the production of many consumables and equipments of daily consumption and use by man. Growing interest in possible health threats posed by endocrine disrupting chemicals (bisphenol-A inclusive), as these substances are in our environment, food, and many consumer products. Therefore, this study aims to determine bisphenol-A effects on the hypothalamo-pituitary-ovarian axis, and role of melatonin in this regard. Forty-two Wistar rats were bred, grouped into 7, with each group consisting of 6 rats. Experimental groups were administered low and high doses of bisphenol-A and melatonin, starting from day 19, and was continued for 7 weeks orally. They were left to develop into full adults and were sacrificed on day 120±4 days. Blood samples, hypothalamus, pituitary and ovarian tissues were excised for biochemical and tissue antioxidants assays as well as genetic studies. Results show elevated gonadotropin and androgen levels. There was disruption of reactive oxygen species in the ovarian tissues, as well as alterations in the expression of genes that regulate reproduction at the hypothalamus and pituitary levels. Conclusion of early exposure to bisphenol-A is associated with prolonged duration of disruption of reproductive functions in female Wistar rats, which persist long after cessation of the exposure. Melatonin antioxidant effects give some promising outturns against bisphenol-A induced toxicities.

Individual and combined effects of BPA, BPS and BPAF on the cardiomyocyte differentiation of embryonic stem cells

Exposure to many kinds of bisphenols (BPs) is common, and the effects of BP mixtures may differ from those of individual BPs. Therefore, evaluating combined exposure effects is necessary. Our study evaluated the individual and combined exposure effects of bisphenol A (BPA), bisphenol S (BPS) and bisphenol AF (BPAF) on embryonic development using an embryonic stem cell test (EST) and a concentration additive (CA) model at relatively high doses to uncover the interaction model of the three BPs. Environmentally relevant concentrations were then used to evaluate the possible effects of the individual and combined BPs at actual human exposure levels. Exposure to relatively high-dose BPA, BPS and BPAF inhibited embryonic stem cell differentiation into cardiomyocytes and exhibited weak embryo toxicity. Individually, BPA, BPS and BPAF inhibited endoderm, mesoderm and ectoderm marker expression but enhanced pluripotency marker expression. Combined exposure to BPs had an additive effect on cardiomyocyte differentiation and embryonic stem cell proliferation based on the CA model. Environmentally relevant individual or combined BP doses (10 ng/ml individual BPA, BPS and BPAF doses or 1 ng/ml and 10 ng/ml BP mixture doses) failed to cause oxidative stress, DNA damage or apoptosis changes in stem cell differentiation. The cardiomyocyte differentiation ratio also did not change significantly. Individual and combined exposure to environmentally relevant BP doses led to a significant increase in collagen expression. BPAF and the combination of BPs increased the type 1 collagen level, while the combination also increased the type 3 collagen level, which may be related to p38 pathway activation. The p38 pathway inhibitor SB203580 inhibited the increase in collagen during cardiomyocyte differentiation caused by low-dose BPs. These results suggest that relatively high-dose BPs in combination have an additive effect on cardiomyocyte differentiation. Low-dose BPs individually and in combination may affect cardiomyocyte collagen through the p38 pathway.

Bisphenol A decreases expression of Insulin-like factor 3 and induces histopathological changes in the Testes of Rats.

Bisphenol A (BPA) is a chemical agent known to have detrimental reproductive and developmental effects. The tissue-specific impacts of BPA exposures and target tissues sensitiveness to BPA are still unclear. The aim of this study was to determine the short- and long-term dose-dependent toxic effects of BPA on rat testes. Forty-eight Wistar albino male rats were divided into four groups each containing 12 rats. To induce toxicity, BPA was administered orally at three different dosages (50, 100, and 200 mg/kg) for 14 and 28 days, respectively. Testis tissues were examined using light and electron microscopy, immunohistochemistry, and biochemical methods. Serum testosterone (T) and luteinizing hormone (LH) levels were measured. Additionally, insulin-like factor 3 (INSL3) as a marker of Leydig cell function was evaluated immunohistochemically. Groups administered high doses of BPA showed severe degenerations such as testicular atrophy, spermatogenic arrest, and interstitial edema in testis. Also, a significant decrease in INSL3 immunoreactivity and serum LH and T levels was found. The results indicated that both increased exposure time and dosage of BPA caused more serious detrimental effects on testes in the rat. Decreased INSL3 and T levels was evidence of Leydig cell function impairment due to BPA.

The effects of bisphenol A on liver proteome and mucus vitellogenin in comparison to plasma as a non-invasive biomarker in immature Siberian sturgeons (Acipenser baerii)

This study was done to evaluate the effects of Bisphenol A (BPA) on Siberian sturgeon (Acipenser baerii). As liver is the main organ in the homeostatic adjustments to stress, we used a proteomics method to address molecular response in this tissue. Also, we compared the levels of vitellogenin in plasma and mucus to propose that the last one be a non-invasive method to analyze this biomarker. The fish received 1, 10, and 100 μg g−1 week−1 BPA intraperitoneally for two weeks. The samples were taken on days 0, 7, and 14. Plasma vitellogenin level increased as the highest value was recorded in the group with 100 μg g−1 week−1 of BPA. Changes in the mucus and blood vitellogenin showed a similar pattern, suggesting that mucus could be used for evaluating the changes in blood vitellogenin. Comparative proteomics was used to determine the proteome of the liver of A. baerii in the highest dose of BPA in comparison with the control. Sixteen proteins were identified that their expression changed at least twice between the studied groups. The proteomic results showed that BPA increased the expression of proteins involved in the detoxification and metabolism, activated glycolysis, and produced necrosis in the liver.