RESUMEN
Butylparaben (BP), a common chemical preservative in cosmetic and pharmaceutical products, has been known to induce oxidative stress and disrupt endocrine function in humans. In contrast, morin, a flavonoid derived from the Moraceae family, exhibits diverse pharmacological properties, including anti-inflammatory and antioxidant. Despite this, the protective role of morin against oxidative stress-induced damage in pancreatic islets remains unclear. Therefore, in this study, we aimed to investigate the potential protective mechanism of morin against oxidative stress-induced damage caused by BP in zebrafish larvae. To achieve this, we exposed the zebrafish larvae to butylparaben (2.5 mg/L) for 5 days, leading to increased oxidative stress and apoptosis in ß-cells. However, our compelling findings revealed that pretreatment with various concentrations of morin effectively reduced mortality and mitigated apoptosis and lipid peroxidation in ß-cells induced by BP exposure. In addition, zebrafish larvae exposed to BP for 5 days exhibited evident ß-cell damage. However, the pretreatment with morin showed promising effects by promoting ß-cell proliferation and lowering glucose levels. Furthermore, gene expression studies indicated that morin pretreatment normalized PEPCK expression while increasing insulin expression in BP-exposed larvae. In conclusion, our findings highlight the potential of morin as a protective agent against BP-induced ß-cell damage in zebrafish larvae. The observed improvements in oxidative stress, apoptosis, and gene expression patterns support the notion that morin could be further explored as a therapeutic candidate to counteract the detrimental effects of BP exposure on pancreatic ß-cells.
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Flavonas , Insulina , Parabenos , Pez Cebra , Animales , Humanos , Larva , Antioxidantes/farmacología , Estrés Oxidativo , Flavonoides/farmacología , Flavonoides/uso terapéuticoRESUMEN
The presence of butylparaben (BP), a prevalent pharmaceutical and personal care product, in surface waters has raised concerns regarding its impact on aquatic ecosystems. Despite its frequent detection, the toxicity of BP to the cyanobacterium Microcystis aeruginosa remains poorly understood. This study investigates the influence of BP on the growth and physiological responses of M. aeruginosa. Results indicate that low concentrations of BP (below 2.5 mg/L) have negligible effects on M. aeruginosa growth, whereas higher concentrations (5 mg/L and 10 mg/L) lead to significant growth inhibition. This inhibition is attributed to the severe disruption of photosynthesis, evidenced by decreased Fv/Fm values and chlorophyll a content. BP exposure also triggers the production of reactive oxygen species (ROS), resulting in elevated activity of antioxidant enzymes. Excessive ROS generation stimulates the production of microcystin-LR (MC-LR). Furthermore, lipid peroxidation and cell membrane damage indicate that high BP concentrations cause cell membrane rupture, facilitating the release of MC-LR into the environment. Transcriptome analysis reveals that BP disrupts energy metabolic processes, particularly affecting genes associated with photosynthesis, carbon fixation, electron transport, glycolysis, and the tricarboxylic acid cycle. These findings underscore the profound physiological impact of BP on M. aeruginosa and highlight its role in stimulating the production and release of MC-LR, thereby amplifying environmental risks in aquatic systems.
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Microcystis , Microcystis/efectos de los fármacos , Microcystis/crecimiento & desarrollo , Microcystis/metabolismo , Microcistinas/biosíntesis , Biomasa , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Toxinas Marinas/biosíntesis , Parabenos/farmacología , Antioxidantes/metabolismoRESUMEN
Parabens have historically served as antimicrobial preservatives in a range of consumables such as food, beverages, medications, and personal care products due to their broad-spectrum antibacterial and antifungal properties. Traditionally, these compounds were believed to exhibit low toxicity, causing minimal irritation, and possessing limited sensitization potential. However, recent evidence suggests that parabens might function as endocrine-disrupting chemicals (EDCs). Consequently, extensive research is underway to elucidate potential human health implications arising from exposure to these substances. Among these parabens, particular concerns have been raised regarding the potential adverse effects of iso-butylparaben (IBP). Studies have specifically highlighted its potential for inducing hormonal disruption, significant ocular damage, and allergic skin reactions. This study aimed to evaluate the prolonged systemic toxicity, semen quality, and estrus cycle in relation to endocrine disruption endpoints, alongside assessing the toxicokinetic behavior of IBP in Sprague-Dawley rats following a 13-week repeated subcutaneous administration. The rats were administered either the vehicle (4% Tween 80) or IBP at dosage levels of 2, 10, and 50 mg/kg/day for 13 weeks. Blood collection for toxicokinetic study was conducted on three specified days: day 1 (1st), day 30 (2nd), and day 91 (3rd). Systemic toxicity assessment and potential endocrine effects were based on various parameters including mortality rates, clinical signs, body weights, food and water consumption, ophthalmological findings, urinalysis, hematological and clinical biochemistry tests, organ weights, necropsy and histopathological findings, estrus cycle regularity, semen quality, and toxicokinetic behavior. The findings revealed that IBP induced local irritation at the injection site in males at doses ≥ 10 mg/kg/day and in females at 50 mg/kg/day; however, systemic toxicity was not observed. Consequently, the no-observed-adverse-effect level (NOAEL) for IBP was determined to be 50 mg/kg/day in rats of both sexes, indicating no impact on the endocrine system. The toxicokinetics of IBP exhibited dose-dependent systemic exposure, reaching a maximum dose of 50 mg/kg/day, and repeated administration over 13 weeks showed no signs of accumulation.
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Disruptores Endocrinos , Ciclo Estral , Parabenos , Ratas Sprague-Dawley , Toxicocinética , Animales , Parabenos/toxicidad , Parabenos/farmacocinética , Parabenos/administración & dosificación , Masculino , Femenino , Ciclo Estral/efectos de los fármacos , Disruptores Endocrinos/toxicidad , Disruptores Endocrinos/farmacocinética , Relación Dosis-Respuesta a Droga , Ratas , Nivel sin Efectos Adversos Observados , Conservadores Farmacéuticos/toxicidad , Conservadores Farmacéuticos/farmacocinética , Conservadores Farmacéuticos/administración & dosificación , Inyecciones SubcutáneasRESUMEN
Butylparaben (BuP) is a common antibacterial preservative utilized extensively in food, medical supplies, cosmetics, and personal care products. The current study reports the use of Zebrafish (Danio rerio) embryos to investigate potential developmental toxicity caused by exposure to BuP. The development of Neural crest cells (NCCs) is highly active during gastrulation in Zebrafish embryos. Thus, we utilized 0.5 mg/L, 0.75 mg/L, and 1 mg/L BuP solutions, respectively, in accordance with the international safety standard dosage. We observed severe craniofacial cartilage deformities, periocular edema, cardiac dysplasia, and delayed otolith development in the Zebrafish larvae 5 days after exposure. The oxidative stress response was significantly enhanced. In addition, the biochemical analysis revealed that the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly reduced relative to the control group, whereas the concentration of malondialdehyde (MDA) was significantly elevated. Furthermore, ALP activity, a marker of osteoblast activity, was also reduced. Moreover, the RT-qPCR results indicated that the expression of chondrocyte marker genes sox9a, sox9b, and col2a1a was down-regulated. In addition, the morphology of maxillofacial chondrocytes was altered in Zebrafish larvae, and the proliferation of cranial NCCs was inhibited. Accordingly, our findings indicate that strong oxidative stress induced by BuP inhibits the proliferation of NCCs in larval Zebrafish, leading to craniofacial deformities.
RESUMEN
Due to Butylparaben (BuP) widespread application in cosmetics, food, pharmaceuticals, and its presence as an environmental residue, human and animal exposure to BuP is common, potentially posing hazards to both human and animal health. Congenital heart disease is already a serious problem. However, the effects of BuP on the developing heart and its underlying mechanisms remain unclear. Here, zebrafish embryos were exposed to environmentally and human-relevant concentrations of BuP (0.6 mg/L, 1.2 mg/L, and 1.8 mg/L, calculated but not measured) at 6 h post-fertilization (hpf) and were treated until 72 hpf. Exposure to BuP led to cardiac morphological defects and cardiac dysfunction in zebrafish embryos, manifesting symptoms similar to systolic heart failure. The etiology of BuP-induced systolic heart failure in zebrafish embryos is multifactorial, including cardiomyocyte apoptosis, endocardial and atrioventricular valve damage, insufficient myocardial energy, impaired Ca2+ homeostasis, depletion of cardiac-resident macrophages, cardiac immune non-responsiveness, and cardiac oxidative stress. However, excessive accumulation of reactive oxygen species (ROS) in the cardiac region and cardiac immunosuppression (depletion of cardiac-resident macrophages and cardiac immune non-responsiveness) may be the predominant factors. In conclusion, this study indicates that BuP is a potential hazardous substance that can cause adverse effects on the developing heart and provides evidence and insights into the pathological mechanisms by which BuP leads to cardiac dysfunction. It may help to prevent the BuP-based congenital heart disease heart failure in human through ameliorating strategies and BuP discharge policies, while raising awareness to prevent the misuse of preservatives.
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Cardiopatías Congénitas , Insuficiencia Cardíaca Sistólica , Animales , Humanos , Pez Cebra , Insuficiencia Cardíaca Sistólica/metabolismo , Insuficiencia Cardíaca Sistólica/patología , Estrés Oxidativo , Cardiopatías Congénitas/inducido químicamente , Terapia de Inmunosupresión , Embrión no MamíferoRESUMEN
Butylparaben is an ubiquitous environmental endocrine disruptor, that is commonly used in cosmetics and personal care product due to its anti-microbial properties. Butylparaben has been shown to cause developmental toxicity, endocrine and metabolic disorders and immune diseases. However, little is known about the impact on female fertility, especially oocyte quality. In the present study, we reported that butylparaben influenced female fertility by showing the disturbed oocyte meiotic capacity and fertilization potential. Specifically, butylparaben results in the oocyte maturation arrest by impairing spindle/chromosome structure and microtubule stability. Besides, butylparaben results in fertilization failure by impairing the dynamics of Juno and ovastacin and the sperm binding ability. Last, single-cell transcriptome analysis showed that butylparaben-induced oocyte deterioration was caused by mitochondrial dysfunction, which led to the accumulation of ROS and occurrence of apoptosis. Collectively, our study indicates that mitochondrial dysfunction and redox perturbation is the major cause of the weakened female fertility expoesd to butylparaben.
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Meiosis , Semen , Masculino , Femenino , Ratones , Animales , Oocitos/metabolismo , Fertilización , FertilidadRESUMEN
Parabens are esters of para-hydroxybenzoic acid that have been used as preservatives in many types of products for decades including agrochemicals, pharmaceuticals, food and cosmetics. This illustrative case study with propylparaben (PP) demonstrates a 10-step read-across (RAX) framework in practice. It aims at establishing a proof-of-concept for the value added by new approach methodologies (NAMs) in read-across (RAX) for use in a next-generation risk assessment (NGRA) in order to assess consumer safety after exposure to PP-containing cosmetics. In addition to structural and physico-chemical properties, in silico information, toxicogenomics, in vitro toxicodynamic, toxicokinetic data from PBK models, and bioactivity data are used to provide evidence of the chemical and biological similarity of PP and analogues and to establish potency trends for observed effects in vitro. The chemical category under consideration is short (C1-C4) linear chain n-alkyl parabens: methylparaben, ethylparaben, propylparaben and butylparaben. The goal of this case study is to illustrate how a practical framework for RAX can be used to fill a hypothetical data gap for reproductive toxicity of the target chemical PP.
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Cosméticos , Parabenos , Cosméticos/química , Cosméticos/toxicidad , Parabenos/química , Parabenos/toxicidad , Conservadores Farmacéuticos/toxicidad , Reproducción , Medición de Riesgo/métodosRESUMEN
Parabens are widely used preservatives in cosmetics and pharmaceutical products and are approved as food additives. These chemicals have been considered safe for many years. However, the literature classifies parabens as endocrine-disrupting chemicals, and an assessment of their influence on the endocrine system and systemic toxicity is important. This study explored long-term systemic toxicity, effects on the endocrine system, and toxicokinetic behavior after repeated subcutaneous administration of butylparaben to Sprague-Dawley rats. Rats were treated with vehicle (4% Tween 80) or butylparaben at dose levels of 2, 10, and 50 mg/kg/day for 13 weeks. Assessment of systemic toxicity and endocrine-disrupting effects was based on mortality; clinical signs; body weight; food and water consumption; ophthalmological findings; urinalysis; hematology and clinical biochemistry; organ weights; necropsy and histopathological findings; regularity and length of the estrous cycle; semen quality; and toxicokinetic behavior. Female uterine weight and estrous cycle, and male semen quality indicated no estrogenic effects. Butylparaben induced local irritation at the injection site in both sexes at a dose of 50 mg/kg/day, but systemic toxicity was not observed. Therefore, the no-observed-adverse-effect level of butylparaben is set at 50 mg/kg/day in rats of both sexes. Butylparaben was without endocrine system effects at this dose. Butylparaben displays dose-dependent systemic exposure up to the maximum dose of 50 mg/kg/day and repeated administration of butylparaben for 13 weeks shows no bioaccumulation.
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Parabenos/toxicidad , Conservadores Farmacéuticos/toxicidad , Toxicocinética , Animales , Relación Dosis-Respuesta a Droga , Ciclo Estral/efectos de los fármacos , Femenino , Inyecciones Subcutáneas , Masculino , Nivel sin Efectos Adversos Observados , Parabenos/administración & dosificación , Conservadores Farmacéuticos/administración & dosificación , Ratas , Ratas Sprague-Dawley , Semen/efectos de los fármacos , Factores SexualesRESUMEN
Parabens are classified as endocrine disrupting chemicals due to their ability to activate several nuclear receptors causing changes in hormones-dependent signalling pathways. Central nervous system of developing organisms is particularly vulnerable to changes in hormonal pathways, which could lead to altered brain function, abnormal behaviour and even diseases later in life. The aim of the present study was to investigate the effects of exposure to butylparaben (BuP), ethylparaben (EtP) and methylparaben (MeP) during early development on nervous system using zebrafish larvae's behavioural models. Zebrafish were exposed until 4 days post fertilization (dpf) to three concentrations of each paraben chosen considering the environmentally realistic concentrations of human exposure and the benchmark-dose lower bound calculated for zebrafish larvae (BuP: 5, 50 and 500 µg/L; EtP: 50, 500 and 5000 µg/L; MeP: 100, 1000 and 10,000 µg/L). Activity in novel and in familiar environment, thigmotaxis, visual startle response and photic synchronization of the behavioural circadian rhythms were analysed at 4, 5 and 6 dpf. Zebrafish larvae exposed to BuP 500 µg/L and EtP 5000 µg/L revealed increased anxiety-like behaviour in novel environment. Larvae treated with 500 µg/L of BuP showed reduced activity in familiar and marginally in unfamiliar environment, and larvae exposed to 5000 µg/L of EtP exhibited hyperactivity in familiar environment. Parabens exposure did not influence the visual startle response and the photic synchronization of circadian rhythms in zebrafish larvae. This research highlighted as the exposure to parabens has the potential to interfere with behavioural development of zebrafish.
Asunto(s)
Disruptores Endocrinos/toxicidad , Parabenos/toxicidad , Pez Cebra , Animales , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Pez Cebra/crecimiento & desarrolloRESUMEN
Anthropogenic chemicals such as parabens and triclosan are used in personal care products. Due to their ability to decrease or prevent bacterial contamination and act as preservatives, these chemicals are used in cosmetic manufacturing processes to increase the shelf life of products. In this study, we assessed the side effects of environmental estrogens (such as the xenoestrogen butylparaben and the antimicrobial agent and preservative triclosan) on thyroid function, brain monoamine levels, and DNA aberration. Forty-two male albino rats were divided into seven groups with six members each: the first group served as control; the second and the third groups were treated with butylparaben 10 and 50 mg/kg body weight, respectively; the fourth and fifth groups were treated with triclosan 10 and 50 mg/kg body weight, respectively; and the sixth and seventh groups were treated with butylparaben plus triclosan 10 and 50 mg/kg body weight, respectively. After 60 days, blood samples were collected and brain specimens were divided into striatum, midbrain, cortex, and thalamus. Thyroid function and levels of monoamines and monoamine metabolites were determined for each brain area. Comet assay was used for brain tissue analysis. The results showed that butylparaben and triclosan and their combinations induced hypothyroidism and disrupted monoamine levels, leading to a decrease in catecholamine and serotonin levels, and accelerated production of 5-hydroxyindoleacetic acid. The obtained data indicate that anthropogenic chemicals such as butylparaben and triclosan have harmful effects on thyroid and brain function and accelerate cell destruction and mutation, as evidenced by single-stranded DNA breaks in the comet assay.
RESUMEN
Parabens are widely used in personal care products due to their antimicrobial effects. Although the toxicity of parabens has been reported, little information is available on the toxicity of butylparaben (BP) on oocyte maturation. Therefore, we investigated the effects of various concentrations of BP (0 µM, 100 µM, 200 µM, 300 µM, 400 µM, and 500 µM) on the in vitro maturation of porcine oocytes. BP supplementation at a concentration greater than 300 µM significantly reduced the proportion of complete cumulus cell expansion and metaphase II oocytes compared to the control. The 300 µM BP significantly decreased fertilization, cleavage, and blastocyst formation rates with lower total cell numbers and a higher rate of apoptosis in blastocysts compared to the control. The BP-treated oocytes showed significantly higher reactive oxygen species (ROS) levels, and lower glutathione (GSH) levels than the control. BP significantly increased the aberrant mitochondrial distribution and decreased mitochondrial function compared to the control. BP-treated oocytes exhibited significantly higher percentage of γ-H2AX, annexin V-positive oocytes and expression of LC3 than the control. In conclusion, we demonstrated that BP impaired oocyte maturation and subsequent embryonic development, by inducing ROS generation and reducing GSH levels. Furthermore, BP disrupted mitochondrial function and triggered DNA damage, early apoptosis, and autophagy in oocytes.
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Desarrollo Embrionario/efectos de los fármacos , Fertilización In Vitro/efectos de los fármacos , Oogénesis/efectos de los fármacos , Parabenos/toxicidad , Animales , Blastocisto/efectos de los fármacos , Blastocisto/metabolismo , Glutatión , Oocitos/efectos de los fármacos , Parabenos/efectos adversos , Especies Reactivas de Oxígeno , Sus scrofa/embriología , Sus scrofa/fisiologíaRESUMEN
In cosmetics and food products, parabens are widely used as antimicrobial agents. Reports have suggested that parabens may be linked to infertility, owing to their effects on basal steroidogenesis properties or their capacity to inflict mitochondrial damage. Despite growing concerns about parabens as endocrine disruptors, it is unclear whether they affect any of these actions in humans, particularly at environmentally relevant concentrations. In this work, an in vitro primary culture of human granulosa cells was used to evaluate steroidogenesis, based on the assessment of progesterone production and regulation of critical steroidogenic genes: CYP11A1, HSD3B1, CYP19A1, and HSD17B1. The effects of two commercially relevant parabens, methylparaben (MPB) and butylparaben (BPB), were screened. Cells were exposed to multiple concentrations ranging from relatively low (typical environmental exposure) to relatively high. The effect was assessed by the parabens' ability to modify steroidogenic genes, progesterone or estradiol production, and on mitochondrial health, by evaluating mitochondrial activity as well as mtDNA content. Neither MPB nor BPB showed any effect over progesterone production or the expression of genes controlling steroid production. Only BPB affected the mitochondria, decreasing mtDNA content at supraphysiological concentrations (1000 nM). Prolonged exposure to these compounds produced no effects in neither of these parameters. In conclusion, neither MPB nor BPB significantly affected basal steroidogenesis in granulosa cells. Although evidence supporting paraben toxicity is prevalent, here we put forth evidence that suggests that parabens do not affect basal steroidogenesis in human granulosa cells.
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Disruptores Endocrinos/toxicidad , Células de la Granulosa/efectos de los fármacos , Parabenos/toxicidad , Progesterona/biosíntesis , Adulto , Aromatasa/genética , Líquidos Corporales/química , Células Cultivadas , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/genética , ADN Mitocondrial/metabolismo , Relación Dosis-Respuesta a Droga , Disruptores Endocrinos/administración & dosificación , Disruptores Endocrinos/análisis , Estradiol Deshidrogenasas/genética , Femenino , Células de la Granulosa/metabolismo , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Modelos Biológicos , Complejos Multienzimáticos/genética , Parabenos/administración & dosificación , Parabenos/análisis , Cultivo Primario de Células , Progesterona Reductasa/genética , Esteroide Isomerasas/genéticaRESUMEN
The aim of the present study was to investigate the kinetics of methylparaben (MPB) and butylparaben (BPB) removal, two emerging pollutants with possible endocrine disrupting effects, from agricultural soil with and without amendment with compost from sewage sludge used as biostimulant. Compound removal is explained by a first-order kinetic model with half-life times of 6.5/6.7 days and 11.4/8.2 days, in presence/absence of compost, for MPB and BPB respectively. % R2 for the fitted model were higher than 96% in all cases. Additionally, isolation of bacteria capable to grow using MPB or BPB as carbon source was also carry out. Laboratory tests demonstrated the ability of these bacteria to biodegrade MPB and BPB from culture media in more than 95% in some cases. These strains showed high ability to biodegrade the compounds. Ten isolates, most of them related to Gram positive bacteria of the genus Bacillus, were identified by 16S rRNA gene sequencing. The study of the enzymatic activities of the isolates revealed both esterase (C4) and esterase-lipase activities.
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Contaminantes del Suelo , Suelo , Bacterias , Parabenos , ARN Ribosómico 16S , Aguas del Alcantarillado , Microbiología del SueloRESUMEN
The effect of treatment with combined butylparaben and triclosan on male gonadal toxicity in weanling rats was investigated. All treated groups experienced atrophy in the ventral prostate and seminal vesicle, likewise significant depletion in the number and motility of sperm. Given individually or combined butylparaben and triclosan, significantly decreased testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Individual treatment with tested compounds caused significant elevation in the E2 level, whereas combined treatment did not alter the E2 level. Testicular DNA damage was recorded in all treated groups. Moreover, the testicular malondialdehyde level was significantly elevated, along with a significant decrease in catalase enzyme activity in all treated groups. Superoxide dismutase enzyme activity was significantly decreased in the butylparaben-treated group, increased in the triclosan-treated group, and nonsignificantly changed the butylparaben-triclosan-treated group. The combined treatment produced an endocrine disturbance with a concomitant induction of testicular oxidative stress, which may represent a common mechanism of endocrine disruptor-mediated dysfunction.
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Daño del ADN , Hormonas Esteroides Gonadales/metabolismo , Estrés Oxidativo/efectos de los fármacos , Parabenos/efectos adversos , Testículo/crecimiento & desarrollo , Triclosán/efectos adversos , Animales , Masculino , Parabenos/farmacología , Ratas , Ratas Wistar , Testículo/patología , Triclosán/farmacologíaRESUMEN
Parabens (PBs) are commonly utilized as preservatives in various commodities. Of all the PBs, methylparaben (MeP) and butylparaben (BuP) are usually found together at similar levels in the aqueous environment. Although a few studies have demonstrated that PBs are neurotoxic when present alone, the neurobehavioral toxic effects and mechanisms of coexisting MeP and BuP at environmental levels has not been determined. Neurobehavior is a sensitive indicator for identifying neurotoxicity of environmental pollutants. Therefore, adult female zebrafish (Danio rerio) were chronic co-exposure of MeP and BuP at environmental levels (5, 50, and 500 ng/L) for 60 d to investigate the effects on neurobehavior, histopathology, oxidative stress, mitochondrial function, neurotransmitters and gene expression. The results demonstrated that chronic co-exposure of MeP and BuP interfered with several behaviors (learning-memory, anxiety, fear, aggressive and shoaling behavior) in addition to known mechanisms of producing oxidative stress and disrupting energy. More intriguingly, chronic co-exposure of MeP and BuP caused retinal vacuolization and apoptosis in the optic tectum zone. It even has further effects on the phototransduction pathway, impairing optesthesia and leading to neurotransmitters dysregulation. These are critical underlying mechanisms resulting in neurobehavioral abnormalities. This study confirms that the pollution of multiple PBs by chronic co-exposure in aquatic environments can result neurobehavioral toxicity. It also suggests that the prolonged effects of PBs on aquatic ecosystems and health require close attention.
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Conducta Animal , Estrés Oxidativo , Parabenos , Contaminantes Químicos del Agua , Pez Cebra , Animales , Pez Cebra/fisiología , Parabenos/toxicidad , Femenino , Conducta Animal/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Estrés Oxidativo/efectos de los fármacos , Contaminación AmbientalRESUMEN
BACKGROUND: Alkylphenols can originate from numerous products containing alkylphenol ethoxylates, including cleaning products, household items, and cosmetics. Some phenols, such as nonylphenol, are known to be endocrine disruptors, and exposure to them is thought to have contributed to the recent increase in allergic diseases such as asthma. However, the impacts of prenatal phenol exposure on asthma development in children are still unclear. METHODS: We analyzed the association between maternal urinary phenol concentrations during early pregnancy and the development of asthma in children at the age of 4, using data from the Japan Environment and Children's Study (JECS), a large-scale nationwide birth cohort study. RESULTS: We recruited 3,513 pairs of mothers and children participating in the Sub-Cohort Study of JECS. We measured 24 phenols, including nitrophenol, parabens, bisphenol, octylphenol, and nonylphenol, in urine samples taken during the first trimester of pregnancy. The urinary levels of these phenols differed markedly, and some showed a broad spectrum of distribution. Methylparaben was detected at high levels in almost every participant (267.7 ng/ml, standard deviation 433.78). Logistic regression analysis revealed that the odds ratio of asthma onset for high exposure to butylparaben was 1.54 (95% confidence interval: 1.11-2.15). Additionally, logistic regression analysis by gender revealed an asthma development odds ratio of 2.09 (95% confidence interval: 1.20-3.65) for males and 0.65 (95% confidence interval: 0.25-1.70) for females born to mothers in whom 4-nonylphenol was detected, suggesting a gender difference. CONCLUSION: Our current analysis using large cohort data suggests that high exposure to butylparaben and low exposure to 4-nonylphenol during pregnancy are risk factors for asthma development in children. These findings establish a valuable foundation for formulating recommendations about prenatal phenol exposure.
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Butylparaben, a common preservative, is widely used in food, pharmaceuticals and personal care products. Epidemiological studies have revealed the close relationship between butylparaben and diabetes; however the mechanisms of action remain unclear. In this study, we administered butylparaben orally to mice and observed that exposure to butylparaben induced glucose intolerance and hyperlipidemia. RNA sequencing results demonstrated that the enrichment of differentially expressed genes was associated with lipid metabolism, bile acid metabolism, and inflammatory response. Western blot results further validated that butylparaben promoted hepatic lipogenesis, inflammation, gluconeogenesis, and insulin resistance through the inhibition of the farnesoid X receptor (FXR) pathway. The FXR agonists alleviated the butylparaben-induced metabolic disorders. Moreover, 16 S rRNA sequencing showed that butylparaben reduced the abundance of Bacteroidetes, S24-7, Lactobacillus, and Streptococcus, and elevated the Firmicutes/Bacteroidetes ratio. The gut microbiota dysbiosis caused by butylparaben led to decreased bile acids (BAs) production and increased inflammatory response, which further induced hepatic glycolipid metabolic disorders. Our results also demonstrated that probiotics attenuated butylparaben-induced disturbances of the gut microbiota and hepatic metabolism. Taken collectively, the findings reveal that butylparaben induced gut microbiota dysbiosis and decreased BAs production, which further inhibited FXR signaling, ultimately contributing to glycolipid metabolic disorders in the liver.
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Microbioma Gastrointestinal , Parabenos , Receptores Citoplasmáticos y Nucleares , Transducción de Señal , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Parabenos/toxicidad , Receptores Citoplasmáticos y Nucleares/metabolismo , Masculino , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL , Glucolípidos/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Enfermedades Metabólicas/inducido químicamente , Enfermedades Metabólicas/metabolismo , Ratones , Disbiosis/inducido químicamente , Conservadores Farmacéuticos/toxicidad , Ácidos y Sales Biliares/metabolismoRESUMEN
Parabens (PBs) are a class of preservatives commonly used in cosmetics and pharmaceuticals. Studies have shown that these compounds may act as endocrine disruptors, affecting thyroxine levels in humans. PBs with longer chain substituents, such as butylparaben (BuP), are less prone to complete biotransformation and are therefore more likely to accumulate in the body. In this study, the effect of high-dose exposure to BuP on thyroid microstructure, ultrastructure, and function was investigated in rats. 50 mg/kg bw per day of BuP was injected subcutaneously into the neck of rats for 4 weeks. Rat thyroid weight, microstructure, and ultrastructure were determined, and the levels of thyroid sodium/iodide symporter (NIS), serum thyroid hormones, and thyroid autoantibodies were measured. The human thyroid cell line was used to study the mechanism of BuP on thyroid epithelial cells. The weight of the thyroid gland of BuP-exposed rats was increased, the structure of the thyroid follicles was irregular and damaged, the mitochondria and rough endoplasmic reticulum were swollen and damaged, and the microvilli at the tip of the epithelium were reduced and disappeared. Serum total T3, total T4, free T3, and free T4 were decreased in BuP-exposed rats, and TSH, peroxidase antibody, and thyroglobulin antibody were increased. In vitro, BuP decreased the level of NIS in thyroid epithelial cells, inhibited proliferation and viability, and induced apoptosis in a dose-dependent manner. This study demonstrated that high-dose exposure to BuP induced structural, ultrastructural, and functional impairment to the thyroid gland of rats, which may be one of the factors leading to hypothyroidism.
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Hipotiroidismo , Parabenos , Ratas , Animales , Humanos , Parabenos/toxicidad , Parabenos/química , Hormonas Tiroideas , Hipotiroidismo/inducido químicamente , Tiroxina , TirotropinaRESUMEN
Butylparaben, a common endocrine disruptor in the environment, is known to be toxic to the reproductive system, heart, and intestines, but its nephrotoxicity has rarely been reported. In order to study the nephrotoxicity and mechanism of butylparaben, we examined the acute and chronic effects on human embryonic kidney cells (HEK293T) and zebrafish. Additionally, we assessed the potential remedial effects of salidroside against butylparaben-induced nephrotoxicity. Our in vitro findings demonstrated oxidative stress and cytotoxicity to HEK293T cells caused by butylparaben. In the zebrafish model, the concentration of butylparaben exposure ranged from 0.5 to 15 µM. An assortment of experimental techniques was employed, including the assessment of kidney tissue morphology using Hematoxylin-Eosin staining, kidney function analysis via fluorescent dextran injection, and gene expression studies related to kidney injury, development, and function. Additionally, butylparaben caused lipid peroxidation in the kidney, thereby damaging glomeruli and renal tubules, which resulted from the downregulation of the PI3K-AKT signaling pathway. Furthermore, salidroside ameliorated butylparaben-induced nephrotoxicity through the PI3K-AKT signaling pathway. This study reveals the seldom-reported kidney toxicity of butylparaben and the protective effect of salidroside against toxicological reactions related to nephrotoxicity. It offers valuable insights into the risks to kidney health posed by environmental toxins.
Asunto(s)
Riñón , Parabenos , Transducción de Señal , Pez Cebra , Animales , Humanos , Regulación hacia Abajo/efectos de los fármacos , Disruptores Endocrinos/toxicidad , Glucósidos/farmacología , Células HEK293 , Riñón/efectos de los fármacos , Riñón/patología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Enfermedades Renales/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Parabenos/toxicidad , Fenoles/toxicidad , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
A novel, cheap and easy-to-construct device and a simple method for partition coefficient determination in liposome/water system based on modified equilibrium dialysis have been developed. The device consists of two vials separated by a semi-permeable membrane, through which the free form of a low molecular weight substance is transported by shaking assisted diffusion. Five test substances, eugenol, carvacrol, thymol, 4-hydroxybenzyl alcohol (4-HBA) and butylparaben were analyzed after equilibration in aqueous phase by three methods, HPLC-UV, GC-MS and DPV with comparable results. This shows the possibility of using the proposed method in any laboratory with any equipment capable of analyzing the substance under study. The liposome/water partition coefficients (log Pl/w) determined for eugenol (2.39), thymol (2.83), carvacrol (2.78) and butylparaben (3.30) are consistent with previously published data. A strong effect of NaCl on the liposome/water partition coefficient was observed. The value of log Pl/w = 1.06 determined for 4-HBA in the presence of 0.15 mol L-1 NaCl in the partitioning liposomal system was considerably lower than in the absence of the salt (log Pl/w = 2.06). The developed method was used to determine the partition coefficient of morphine in liposome/water system without NaCl (log Pl/w = 2.65) under given conditions.