Toxicity Of Bisphenol A Research Articles

Magnetic biochar derived from dairy manure for peroxymonosulfate activation towards bisphenol A degradation: Kinetics, electron transfer mechanism, and environmental toxicity

Magnetic biochar (MBC) was derived from dairy manure and characterized for understanding the impact of surface characters on PMS activation towards bisphenol A (BPA) degradation. MBC showed high catalytic activity for PMS and kept high catalytic activity under various water matrices. Moreover, the ESR spectra and quenching tests demonstrated that SO4−, OH, and 1O2 were active species for BPA degradation. Electrochemical data indicated that MBC possessed excellent electron transfer property and donated electron from its surface unpaired electron, which enhanced the BPA degradation. Environmental toxicity assay indicated that the toxicity of BPA could be reduced remarkably after MBC-PMS advanced oxidation treatment. Thus, this work will provide a promising strategy to resource agricultural waste and degrade BPA in water treatment.

Exposure to bisphenol A induced oxidative stress, cell death and impaired epithelial homeostasis in the adult Drosophila melanogaster midgut

Recently, the chemical compound Bisphenol A (BPA) has been attracting worldwide attention due to its various toxic effects in animals, including reprotoxicity, neurotoxicity, hepatoxicity, and nephrotoxicity. Here, the midgut of adult Drosophila melanogaster (D. melanogaster), an invertebrate model organism, was employed to investigate the gastrointestinal toxicity of BPA in D. melanogaster and explore its underlying mechanisms of action in insects. As a result, exposure of flies to 0.5 mM BPA resulted in a dramatic morphological alteration of D. melanogaster midgut and decrease in survival rates and climbing ability of flies. Further study indicated that BPA induced high levels of oxidative stress in D. melanogaster midgut due to the imbalance between the production of reactive oxygen species and the activities of cellular antioxidant enzymes, including glutathione-S-transferase, catalase and superoxide dismutase. Oxidative stress induced by BPA then caused intestinal epithelial cell death and gut barrier dysfunction and elevated gut permeability, leading to oxidative injury of midgut epithelium. Antioxidant vitamin E alleviated midgut injury induced by BPA. Subsequently, BPA-induced oxidative injury of midgut further stimulated the proliferation of intestinal stem cell (ISC) and ISC-mediated midgut regeneration, but did not alter cell fate determination of ISCs in Drosophila midgut. Meanwhile, activation of Jun N-terminal kinase signal pathway was found to be required for BPA-induced cell death and tissue regeneration in midgut. Collectively, the present study provided additional evidence from an invertebrate model organism that BPA exposure induced gastrointestinal toxicity in D. melanogaster and further extended our understanding of the molecular mechanisms mediating BPA toxicity in insects.

Hematological changes, redox imbalance, and changes in Na+/K+-ATPase activity caused by bisphenol-A and the integrated biomarker responses in Labeo rohita (Hamilton, 1822)

Bisphenol-A (BPA) is a plasticizer commonly used in the plastics industry to manufacture plastic materials. It is abundant in aquatic ecosystems, resulting in increased contamination and lower concentrations that may represent a significant threat to the aquatic system. Hence in the present study, an Indian major carp, Labeo rohita, was exposed to two different BPA concentrations (1 and 10 μg/L) for 30 days. Compared to control, the chronic effects resulted in significant alterations in red blood cell (RBC) and white blood cells (WBC) count. The exposure to BPA caused significant changes in antioxidant activity in gill, liver, and kidney tissues (inferred by catalase, glutathione peroxidase, and glutathione S-transferase activity) in L. rohita. Regarding lipid peroxidation (LPO), we observed an increase in liver and kidney alteration, while LPO was noted in gill tissue compared to the control. Furthermore, increased Na+/K+-ATPase activity was observed in gills at the end of the 10th day and a gradual decrease at the end of the 30th day. These results indicated that exposure to BPA alters the RBC and WBC levels, antioxidant enzyme activity (gills, liver, and kidney), and Na+/K+-ATPase activity in the gill of L. rohita exposed to BPA (at 1 and 10 μg/L). Therefore, our findings will help us gain better insight into the toxicity of BPA in freshwater ichthyofauna.

Lycopene protects against Bisphenol A induced toxicity on the submandibular salivary glands via the upregulation of PPAR-γ and modulation of Wnt/β-catenin signaling

Background and aimThe submandibular salivary glands (SMG) represent a suitable model for studying epithelial cell growth and differentiation. Bisphenol A (BPA) is a xenoestrogen, synthesized to produce polymers such as polycarbonates and epoxy resins. There are concerns about the occurrence of BPA in food, water as well as its appearance in human tissues and body fluids. Lycopene (LYC) is a carotenoid compound that exerts antioxidant and anti-inflammatory properties. This work was performed to study possible protective effect of LYC against BPA toxicity in SMG. Material and Methods40 albino rats were divided into 4 groups; Group I: served as controls. Group II: rats received LYC (4 mg/kg, p.o), Group III: rats received BPA (10 mg/kg, p.o) and Group IV: rats received LYC (4 mg/kg, p.o) and BPA (10 mg/kg, p.o). All drugs were administered for 45 days then under anesthesia, rats were sacrificed. The SMG specimens were taken for histological and biochemical studies. ResultsBPA resulted in a significant rise of malondialdehyde, tumor necrosis factor-α and interleukine-1β. In contrast, the tissue levels of glutathione and PPAR-γ were significantly decreased. BPA activated Wnt/β-catenin pathway evidenced by upregulating WNT3a, β-catenin and c-myc expression. Moreover, SMG of BPA showed degenerative changes that affected the parenchymal and stromal elements of the glands. The immunohistochemical localization of cytokeratin 5,6 and 18 of BPA rats revealed weak immunostaining of the serous secretory cells, myoepithelial cells and ductal cells. Upon treatment with LYC, glutathione and PPAR-γ were restored. ConclusionLYC acted as a protective agent against BPA-induced pathological changes in SMG.

Protective effects of a polyherbal medicine, Majoon Suranjan against bisphenol-A induced genetic, oxidative and tissue damages

Bisphenol-A (BPA) is a toxic chemical largely produced and used in polycarbonate plastics worldwide. Majoon Suranjan (MS), a polyherbal formulation, is used as an anti-inflammatory medicine against rheumatoid arthritis. The present study aimed to evaluate BPA-induced toxicity and its possible amelioration by MS. To test our hypothesis, we performed gas chromatography-mass spectrometry (GC-MS) analysis, DNA interaction studies, genotoxicity tests, oxidative stress parameters, and histopathological examinations. GC-MS profiling of MS revealed the presence of various anti-oxidant compounds. DNA interaction studies showed that both chemicals intercalate between DNA base pairs. Next, we observed BPA-induced genotoxicity and oxidative damage. The observed effects might be due to BPA-induced reactive oxygen species production. Further, BPA changed the anti-oxidant enzyme activities, increased the malondialdehyde, alanine aminotransferase, alkaline phosphatase, and total bilirubin levels, and caused gross damage to the liver and kidney. Interestingly, these effects were significantly reversed by MS. In conclusion, MS shows protective effects against BPA-induced toxicity and could be a potential alternative medicine against BPA toxicity, especially in third-world countries where BPA uses are not strictly regulated. Highlights: Bisphenol-A (BPA) induces multiple toxic effects. BPA induces genotoxicity, oxidative and tissue damage. Majoon Suranjan (MS) ameliorates the BPA induced toxic effects. GC-MS profiling show various active anti-oxidant compounds in MS. MS is anti-genotoxic, anti-oxidant, and hepato-renal protective

Zinc Deficiency Exacerbates Bisphenol A-Induced Hepatic and Renal Damage: Delineation of Molecular Mechanisms.

Zinc (Zn) plays an important role in the maintenance of redox status in the biological system. Zn deficiency has been found to be associated with negative effects on the functioning of many organ systems, including hepatic and renal systems. Bisphenol A (BPA) can alter Zn homeostasis and perturb the physiological system by provoking oxidative stress, which can lead to damage of different organs such as reproductive, immune, neuroendocrine, hepatic and renal systems. The present study aims to investigate the toxicity of BPA in Zn deficient condition in the liver and kidney of rat and to correlate its synergistic actions. Zn deficiency was induced by feeding Zn-deficient diet (ZDD), and BPA was administered orally (100mg/kg/d). Male Sprague-Dawley rats were divided into four groups: NPD + Vehicle (normal feed and water), NPD + BPA (100mg/kg/d), ZDD + Vehicle (fed with Zn-deficient diet only) and ZDD + BPA (Zn-deficient diet + BPA; 100mg/kg/d) for 8weeks. Biochemical, histopathological, TUNEL assay and protein expression profiles were determined to decipher the oxidative damage induced by ZDD and the toxicant BPA. Expression profile of nuclear factor erythroid 2-related factor 2, proliferating cell nuclear antigen, kelch-like ECH-associated protein 1, superoxide dismutase-1, metallothionein and apoptosis incidence showed that ZDD and BPA have a synergistic exacerbation effect on the liver and kidney of rat.

Multi-omics approaches for remediation of bisphenol A: Toxicity, risk analysis, road blocks and research perspectives

In this “plastic era” with the increased use of plastic in day today's life the accumulation of its degraded products like microplastics or plastic additives such as Bisphenol A(BPA) is also increasing. BPA is an endocrine-disrupting chemical used as a plasticizing agent in clear plastic, building materials, coatings, and epoxy resin. Several enzymes including laccases and lipases have been studied for the reduction of BPA toxicity. Over the decades of encountering these toxicants, microorganisms have evolved to degrade different classes of plastic additives. Since the degradation of BPA is a long process thus meta-omics approaches have been employed to identify the active microbiota and microbial dynamics involved in the mitigation of BPA. It is also necessary to investigate the impact of processing activities on transit of BPA in food items and to limit its entrance in food world. This review summarizes a comprehensive overview on BPA sources, toxicity, bio-based mitigation approaches along with a deeper understanding of multi-omics approaches for its reduction and risk analysis. Knowledge gaps and opportunities have been comprehensively compiled that would aid the state-of-the-art information in the available literature for the researchers to further address this issue.

Effects of Bisphenol A Stress on Activated Sludge in Sequential Batch Reactors and Functional Recovery

This study assessed the toxic effects of bisphenol A (BPA) on the microbial community and the function of activated sludge in sequencing batch reactors (SBRs). The toxicity of BPA was mitigated through dosing sludge with Rhodococcus Req-001. BPA reduced the biomass of sludge, and the proportion of viable bacteria decreased with the aggravation of BPA pollution. BPA affected the secretion of extracellular polymeric substances (EPSs), increased the ratio of polysaccharide to protein, and deteriorated the sedimentation performance of sludge. BPA decreased the abundances of functional bacteria involved in the degradation of organic matter and water purification, including Polaromonas, Dechloromonas, and Nitrospira, and the water purification capacity of the reactor decreased. Req-001 enhanced the BPA removal efficiency by 15%, and increased ammonia nitrogen and phosphorus removal by 8.8% and 22.7%, respectively. The functional recovery ability of the sludge system and the high removal ability of Req-001 make it a promising specie for use in BPA bioremediation. This study combined the effect of BPA on activated sludge and reactor performance with the microbial community, clarified the toxic mechanism of BPA on activated sludge, and therefore provides a theoretical basis and potential solutions to help WWTPs cope with the toxic effects of BPA.

Internal electric field modulated BiOI nanoparticle/Bi2W0.25Mo0.75O6 microspheic p-n heterojunctions assisted by persulfate activation for enhancing simulated-sunlight-driven BPA degradation and toxicity reduction

A facile microwave solvothermal method was employed to synthesize a BiOI/Bi2W0.25Mo0.75O6p-n heterostructure by epitaxially growing BiOI layer on the Bi2W0.25Mo0.75O6 microspherical surface, obtaining a three-dimensional spherical structure. Then, an effective photocatalytic oxidation system was established by adding persulfate (PS). Experimental results showed that 5%BiOI/Bi2W0.25Mo0.75O6 heterojunction photocatalysts improved the photocatalytic performance better than the pure BiOI and Bi2W0.25Mo0.75O6. The degradation and mineralization efficiencies of bisphenol A (BPA) in the presence of PS were 100% and 84.5% within 30 and 60 min. Radical quenching and electron spin resonance experiments also revealed the contribution of the active species in the photocatalytic degradation of the BPA system to be in the order of h+ ≈ ·O2− > ·OH/SO4−·. Subsequently, aimed at further enhancing the photocatalytic activity based on the band structure analysis, the fast charge transfer mechanism derived via the interfacial internal electric field of the p-n heterojunction was investigated. The possible degradation pathways were determined by LC-MS analysis and density functional theoretical calculation, and the single and mixed toxicities of the degradation products were evaluated by Toxicity Estimation Software Tool (T.E.S.T.) and Escherichia coli (E. coli) growth inhibition experiments. The overall results confirm the safety of the degradation process. This work offers a facile approach for designing efficient p-n type heterojunction photocatalysts with excellent photocatalytic properties for use in water remediation.

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.

Bibliometric Analysis of the Toxicity of Bisphenol A.

Bisphenol A (BPA) is used worldwide and research on the toxicity of BPA has advanced rapidly in the last few decades. This study aimed to evaluate the global scientific output of toxicity of BPA and explore the hot spots and research trends. All available articles related to the toxicity of BPA until 2022 were retrieved from the Web of Science Core Collection database. The VOSviewer, a bibliometric analysis software, was used to analyze the information of included articles, including countries/institutions, international cooperation, journals, citations, and keywords. Among 1644 retrieved articles, 1611 eligible studies were identified for analysis, and the annual publications increased with time in the past three decades. China and the United States were the most active contributors in this field. Chinese Academy of Sciences and the Dow chemical company conducted relatively more research than others about BPA toxicity. The journal “Chemosphere” published the most studies on “BPA toxicity”. Before 2015, most research focused on estrogenic activity and the test system mainly utilized animal experiments. However, in recent years, research related to toxic mechanisms of BPA at the cellular level and the toxicity of its analogs have received widespread attention. Considering some critical research gaps, future research on BPA toxicology should probably focus on the molecular biology of toxic mechanism, mixture toxicity, and co-exposure of BPA substitutes. This study will help researchers understand past and current research trends, hot spots, and trends of toxicity studies of BPA and, thus, contribute to further research and risk management of BPA.

Neuroprotective effects of 18β-glycyrrhetinic acid against bisphenol A-induced neurotoxicity in rats: involvement of neuronal apoptosis, endoplasmic reticulum stress and JAK1/STAT1 signaling pathway

The exposure to bisphenol A (BPA) is inevitable owing to its common use in the production of polycarbonate plastics. Studies to reduce side effects are gaining importance since BPA causes severe toxicities in important tissues such as testes, lungs, brain, liver and kidney. The current study was planned to study ameliorative effect of 18β-glycyrrhetinic acid (18β-GA) on BPA induced neurotoxicity. Fourty Wistar albino rats were divided into five equal groups as follows: I-Control group, II-18β-GA group (100mg/kg), III- BPA group (250mg/kg), IV-250mg/kg BPA + 50mg/kg 18β-GA group, V-250mg/kg BPA + 100mg/kg 18β-GA group. BPA intoxication was associated with increased MDA level while reduced GSH concentration, activities of glutathione peroxidase, superoxide dismutase, and catalase. BPA supplementation caused apoptosis in the brain by up-regulating caspase-3 and Bax levels and down-regulating Bcl-2. BPA also caused endoplasmic reticulum (ER) stress by increasing mRNA transcript levels of PERK, IRE1, ATF-6 and GRP78. Additionally, it was observed that BPA administration activated JAK1/STAT1 signaling pathway and levels of TNF-α, NF-κB, p38 MAPK and JNK in the brain. However, co-treatment with 18β-GA at a dose of 50 and 100mg/kg considerably ameliorated oxidative stress, inflammation, apoptosis, ER stress and JAK1/STAT1 signaling pathway in brain tissue. Overall, the data of this study indicate that brain damage associated with BPA toxicity could be ameliorated by 18β-GA administration.

The influence of microplastics on the toxic effects and biodegradation of bisphenol A in the microalgae Chlorella pyrenoidosa

Bisphenol A (BPA) and polystyrene (PS) microplastics have attracted much attention because they are widely distributed in the environment, while their combined toxicity to aquatic organisms has rarely been studied. Therefore, this study explored the impact of microplastics on the toxic effects and biodegradation of BPA to the microalgae Chlorella pyrenoidosa. The results indicated that during the 16 days culture, PS (5 mg/L) increased the growth inhibition of BPA (1 mg/L and 10 mg/L) on C. pyrenoidosa compared to without PS. Similarly, PS (5 mg/L and 100 mg/L) also increased the degradation efficiency of BPA (1 mg/L and 10 mg/L) by algae. However, the changes of the chlorophyll content and the Fv/Fm value were opposite due to the hermetic and shading effect. Moreover, this study also found that five intermediates were formed during BPA degradation process because of the presence of oxidoreductase and glycosyltransferase. The results of the study provided vital information on the effect of PS on the toxicity and biodegradation of BPA to microalgal.

Mito-TEMPO protects against bisphenol-A-induced testicular toxicity: an in vivo study

Bisphenol-A (BPA) is a common environmental toxin which alters testicular function in both animals and humans. BPA exerts its cytotoxic potential by altering mitochondrial oxidative stress and functioning. Therefore, protecting mitochondria from oxidative stress may prevent BPA-induced testicular damage. In the present study, modulation of BPA toxicity by mitochondria-targeted antioxidant, mito-TEMPO was studied in male Wistar rats. Rats were administered mito-TEMPO (0.1 mg/kg b.w, i.p.) twice a week, followed by BPA (10 mg/kg b.w., orally) once a week for 4 weeks. After 4 weeks, sperm parameters were evaluated in the testis along with histopathological analysis. The mitochondrial oxidative stress, mitochondrial membrane potential (MMP) and enzymatic activity of mitochondrial complex II and IV were estimated in the testicular tissue. Pretreatment of mito-TEMPO protected animals from toxic effects of BPA as indicated by the normalization of sperm parameters and preserved histoarchitecture of testis. BPA treatment to animals significantly increased mitochondrial reactive oxygen species (ROS) and lipid peroxidation (LPO). A significant decrease in the activity of mitochondrial complex II was also observed after BPA exposure whereas, mitochondrial complex II activity was increased. In addition, an increase in MMP was also observed in BPA group. Mito-TEMPO successfully normalized mitochondrial ROS and LPO formation. Similar normalization effect was also noted in the activity of mitochondrial complex II, complex IV, and MMP. Results suggested that mito-TEMPO pretreatment significantly protected BPA-induced oxidative stress and thereby mito-TEMPO effectively prevented testicular damage.

Positive effects of Epigallocatechin-3-gallate (EGCG) intervention on insulin resistance and gut microbial dysbiosis induced by bisphenol A

Schematic illustration of ameliorative effects of EGCG on BPA-induced insulin resistance. • EGCG intervention successfully ameliorated insulin resistance and impaired insulin sensitivity induced by BPA exposure. • EGCG intervention restored serious damage of gut tight junctions. • EGCG effectively improved intestinal flora disorder and increased gut short chain fatty acids level. Bisphenol A (BPA), a plasticizer, is widely believed to cause metabolic disorders. However, an effective intervention is still absent. This study investigated the beneficial effects of Epigallocatechin-3-gallate (EGCG) on insulin resistance and microbial disturbance induced by BPA. The serum glucose, insulin, total triglyceride, and total cholesterol were decreased in BPA-treated mice after the intervention of EGCG. The sensitivity of insulin signals in peripheral tissue was improved by modulating the phosphorylation of IRS-1, Akt, and GSK-3β. In addition, 16S rRNA analysis for fecal microbiota showed the relative abundance of Ruminiclostridium , Blautia , unidentified_Ruminococcaceae , and Candidatus_Saccharimonas were restored by the high dose of EGCG. Furthermore, EGCG increased the concentrations of fecal short-chain fatty acids and protected the gut barrier impaired by BPA. Overall, our results demonstrated the positive effects of EGCG on BPA-induced insulin resistance and gut microbial dysbiosis. The current study provides a potential treatment for the chronic metabolic toxicity of BPA.

Bisphenol A aggravates renal apoptosis and necroptosis in selenium-deficient chickens via oxidative stress and PI3K/AKT pathway.

Bisphenol A (BPA) in the environment can have deleterious effects on humans and animals. BPA can exert nephrotoxicity by inducing oxidative stress. Selenium (Se) deficiency can specifically impair kidney tissues and additionally show a synergistic effect on the toxicity of several environmental chemicals. However, the toxic effects of BPA on the chicken kidney and whether Se deficiency produces synergistic effects on the toxicity of BPA remain poorly understood. Herein, we established BPA exposure models and Se deficiency model in vivo and in vitro, and described the discovery path of BPA aggravation on apoptosis and necroptosis in Se-deficient chicken kidneys via regulation of oxidative stress and phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) signaling pathway. We found that BPA exposure increasedreactive oxygen species and malondialdehyde levels, reduced activities of catalase, GPx,and superoxide dismutase, downregulated PI3Kand AKT expressions, activated Bcl/Bax-Caspase 9-Caspase 3, and receptor-interacting protein kinase 1/mixed lineage kinase domain-like protein signaling pathways, resulting in apoptosis and necroptosis in the chicken kidney. In addition, Se deficiency significantly promoted the expression of renal apoptosis and necroptosis in BPA-exposed chicken kidneys. Altogether, our results showed that BPA aggravates apoptosis and necroptosis in Se-deficient chicken kidneys via regulation of oxidative stress and PI3K/AKT signaling pathway. Our findings elucidate the mechanism of BPA nephrotoxicity and Se deficiency exacerbation toxicity in chickens and will provide great significance for the protection of the ecological environment and animal health.

Covalent Protein Modification: An Unignorable Factor for Bisphenol A-Induced Hepatotoxicity.

Covalent modification of proteins by reactive pollutants/metabolites might trigger various toxicities resulting from the disruption of protein structures and/or functions, which is critical for understanding the mechanism of pollutants-induced toxicity. However, this mechanism has rarely been touched on due to the lack of a methodology. In this research, the protein modification of bisphenol A (BPA) in rats was characterized using a series of liquid chromatography-tandem mass spectrometry (LC-MS) approaches. BPA-modified cysteine (Cys1) was first released from proteins via enzymatic hydrolysis and identified using LC-MS. Moreover, the positive correlation between Cys1 and hepatotoxicity indicated the involvement of protein modification in BPA toxicity. Then, in vitro incubation of BPA with amino acids and protein confirmed that BPA could specifically modify cysteine residues of proteins after bioactivation and provided four additional modification patterns. Finally, 24 BPA-modified proteins were identified from the liver of BPA-exposed rats using proteomic analysis, and they were mainly enriched in oxidative stress-related pathways. The modification on superoxide dismutases, catalase, and glutathione S-transferases disrupted their enzymatic functions, leading to oxidative damage. These results revealed that the covalent protein modification is an unignorable factor for BPA hepatotoxicity. Moreover, the workflow can be applied to identify protein adducts of other emerging contaminants and possible risk.

Acute and Chronic Toxicity of Binary Mixtures of Bisphenol A and Heavy Metals.

Bisphenol A (BPA) and heavy metals are widespread contaminants in the environment. However, the combined toxicities of these contaminants are still unknown. In this study, the bioluminescent bacteria Vibrio qinghaiensis Q67 was used to detect the single and combined toxicities of BPA and heavy metals, then the joint effects of these contaminants were evaluated. The results show that chronic toxicities of chromium (Cr), cadmium (Cd), lead (Pb), arsenic (As), mercury (Hg), nickel (Ni), and BPA were time–dependent; in fact, the acute toxicities of these contaminants were stronger than the chronic toxicities. Furthermore, the combined toxicities of BPA and heavy metals displayed BPA + Hg > BPA + Cr > BPA + As > BPA + Ni > BPA + Pb > BPA + Cd in the acute test and BPA + Hg > BPA + Cd > BPA + As > BPA + Cd in the chronic test, which suggested that the combined toxicity of BPA and Hg was stronger than that of other mixtures in acute as well as chronic tests. Additionally, both CA and IA models underestimated the toxicities of mixtures at low concentrations but overestimated them at high concentrations, which indicates that CA and IA models were not suitable to predict the toxicities of mixtures of BPA and heavy metals. Moreover, the joint effects of BPA and heavy metals mainly showed antagonism and additive in the context of acute exposure but synergism and additive in the context of chronic exposure. Indeed, the difference in the joint effects on acute and chronic exposure can be explained by the possibility that mixtures inhibited cell growth and luminescence in chronic cultivation. The chronic toxicity of the mixture should be considered if the mixture results in the inhibition of the growth of cells.

Assessing the toxicity of bisphenol A and its six alternatives on zebrafish embryo/larvae.

Bisphenol A (BPA) analogues are gradually replacing BPA in the plastics industry. Whether these alternatives are indeed safer than BPA itself, however, remains unclear. Here, we studied the toxicity of BPA and six of its alternatives-BPB, BPC, BPE, BPF, BPAF, and BPAP-using zebrafish embryos/larvae. According to their half lethal concentration (LC50) values, the acute toxicity of BPA and six alternative bisphenols to zebrafish embryos, from highest to lowest, was BPAP ≈ BPAF > BPC > BPB > BPA > BPE > BPF. Under nonlethal concentrations, the tested bisphenols had different toxic effects on development in terms of reducing the hatching rate, frequency of spontaneous movements, and heart rate in the embryo, as well as inducing yolk sac edema, pericardial edema, and spinal deformation in the larvae. The estrogenic activity of BPE, BPF, and BPAF was higher than that of BPA, as shown by vtg1 expression assays. Moreover, BPA and its alternatives increased SOD activity and cell apoptosis in embryos/larvae under nonlethal concentrations. Our findings indicate that BPA alternatives may not be safer than BPA in zebrafish, and that these BPA alternatives should be applied with caution.

Dietary Zinc Deficiency Increases Bisphenol A Toxicity in Diabetic Rat: Studies on the Testicular and Epididymal Pathophysiology

Bisphenol A (BPA), an endocrine disrupter extensively used in plastics products, that causes male reproductive dysfunction in humans and experimental systems. Type 1 diabetes (T1D) associates hyperglycaemia dysregulate the spermatogenesis and antioxidant status in the testes, which negatively impact on male fertility in adults. Dietary zinc (Zn) deficiency is a global health concern, because majority of the individuals are suffering from certain range of Zn‐deficiency. Zn plays an important role in the regulation and maintenance of testicular physiology and the overall reproductive health. The present study was aimed to investigate the influence of Zn‐deficiency on BPA induced germinal cell and male gonadal toxicity in diabetic rat. Sprague Dawley rats (4 weeks old) were randomly divided into eight different groups; like control (standard pellet diet and aquapure drinking water), BPA (10 mg/kg/day), Zn‐deficient diet (ZDD; Zn‐deficient diet), diabetic (DIA), BPA+ZDD, BPA+DIA, ZDD+DIA and BPA+ZDD+DIA for four weeks. Diabetes was induced by injecting single dose of streptozotocin (55 mg/kg) freshly prepared in cold citrate buffer at pH 4.5. The evaluation of various end‐points such as assessment of body and organ weights, biochemical estimations, sperm parameters. testes and epididymis histopathology, quantification of testicular DNA damage and sperm apoptosis were conducted. Testicular 8‐OHdG immunoexpression as well as catalase and OCT4 expressions were carried out by western blot analysis. The results showed that dietary Zn‐deficient condition significantly increased the BPA toxicity by decreasing body and organ weight, serum albumin and increasing glucose, SGPT, SGOT and BUN significantly in diabetic condition. Further, significant decrease in sperm count, sperm motility and increase in sperm deformities were observed. The Zn‐deficiency significantly increased the BPA induced testicular and epididymal tissue injury, elevated testicular 8‐OHdG immunoexpression and sperm apoptosis in diabetic rat. Moreover, BPA exposure significantly decreased the testicular catalase and OCT4 expressions in dietary Zn‐deficient diabetic rat. The present results concluded that dietary Zn‐deficiency exacerbated the BPA induced gonadal toxicity by hypogonadism, increased sperm abnormalities, testicular and epididymal cellular damage, testicular DNA damages, sperm apoptosis as well as decreased the testicular catalase and OCT4 expressions in diabetic rat.