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1.
J Hazard Mater ; 465: 133512, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38232552

ABSTRACT

Parabens, a group of alkyl esters of p-hydroxybenzoic acid, have been found in aquatic systems in particular, leading to concerns about their potential impact on ecosystems. This study investigated the effects of three commonly used parabens, methylparaben (MeP), ethylparaben (EtP), and propylparaben (PrP), on the brackish water flea Diaphanosoma celebensis. The results showed that PrP had the most adverse impact on survival rates, followed by EtP and MeP, while MeP and EtP induced significant adverse effects on reproductive performance. A transcriptome analysis revealed significant differential gene expression patterns in response to paraben exposure, with MeP associated with the most significant effects. MeP and EtP exposure produced greater disruption in the microbiota of D. celebensis than did PrP compared with control groups, and we identified eight key microbiota, including Ruegeria and Roseovarius. Correlation analysis between transcriptome and microbiome data revealed key interactions between specific microbiota and host gene expression. Certain microbial taxa were associated with specific genes (e.g. cuticle related genes) and toxicological pathways, shedding light on the complex molecular response and in vivo toxicity effects of parabens. These findings contribute to a deeper understanding of the molecular mechanisms underlying paraben toxicity and highlight the importance of considering the ecological impact of chemical contaminants in aquatic ecosystems.


Subject(s)
Cladocera , Parabens , Animals , Parabens/analysis , Transcriptome , Ecosystem , Saline Waters
2.
Food Sci Biotechnol ; 32(9): 1173-1183, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37362818

ABSTRACT

In this study, an analytical method was established and validated to determine the preservatives such as dehydroacetic acid, benzoic acid, sorbic acid, methylparaben and ethylparaben. The level of preservatives was measured by solvent extraction method adding purification process with carrez reagent and by high-performance liquid chromatography (HPLC). The developed analytical method was successfully applied to determine the concentration of preservatives in various food samples including jam, cheese and soy sauce, displaying high accuracy (recoveries between 87.8% and 110%) and precision (%RSD less than 5.92% and 7.72% for intra-day and inter-day, respectively). To verify the applicability of the improved test method, selected 13 food items and collected 521 samples were monitored. As a result, all the cases met the Korea standard guidelines. Consequently, this study is expected to contribute to the safety management of preservatives for domestic distribution and imported food.

3.
Turk J Pharm Sci ; 20(1): 35-38, 2023 Mar 02.
Article in English | MEDLINE | ID: mdl-36864581

ABSTRACT

Objectives: The development of antimicrobial molecules discussed with considerable achievement over the past decades provided many classes of semisynthetic or synthetic compounds. Resistance to many antimicrobial agents requires the discovery of novel molecules. Materials and Methods: In this study, ten ethylparaben hydrazide-hydrazone derivatives, the previously reported, were evaluated for their in vitro antibacterial and antifungal activities. The microbroth dilution method was used for the determination of the minimum inhibitory concentration (MIC) values of the novel molecules. Results: The antimicrobial activities of the molecules were found in a wide range with MIC values of 2-256 µg/mL. The synthesized compounds showed good to moderate antimicrobial activity compared with the standards. Among the synthesized molecules, compound 3g showed the best antimicrobial activity at 2 µg/mL against Staphylococcus aureus strain (ATCC 29213). Conclusion: Ethylparaben hydrazide-hydrazone compounds in our study were found to have antimicrobial activities. Ethylparaben is currently used as an antibacterial agent and preservative for preparations. These studies are necessary since they detect the relationship between the substitutions and activity.

4.
Sci Total Environ ; 842: 156785, 2022 Oct 10.
Article in English | MEDLINE | ID: mdl-35752233

ABSTRACT

Ethylparaben (EP), one of the parabens, a ubiquitous food and cosmetic preservatives, has caused widespread concern due to its health risks. Recently, studies have found that parabens exposure during pregnancy is negatively correlated with fetal and early childhood development. However, studies about EP on embryo development are few. In this study, the cardiotoxicity effects of EP concentrations ranging from 0 to 20 mg/L on zebrafish embryo development were explored. Results showed that EP exposure induce abnormal cardiac function and morphology, mainly manifested as pericardial effusion and abnormal heart rate in early-stage development of zebrafish embryos. Through transcriptome sequencing followed by Gene Ontology enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we further confirmed that EP exposure ultimately leads to cardiac morphologic abnormalities via the following three mechanisms: 1. Disruption of the retinoic acid signaling pathway related to original cardiac catheter development; 2. Inhibition of gene expression related to myocardial contraction; 3. Orientation development disturbance of heart tube. Moreover, O-Dianisidine staining, whole-mount in situ hybridization at 30 and 48 hours post fertilization (hpf) and hematoxylin-eosin staining results all confirmed the decreased heart's return blood volume, misoriented heart tubes toward either the right or the middle side, and heart loop defects. For the first time, we explored the mechanism by which EP exposure causes abnormal heart development in zebrafish embryos, laying the foundation for further revealing of the EP toxicity on embryonic development.


Subject(s)
Parabens , Zebrafish , Animals , Cardiotoxicity , Child, Preschool , Embryo, Nonmammalian , Gene Expression Profiling , Humans , Parabens/metabolism , Parabens/toxicity , Transcriptome
5.
Regul Toxicol Pharmacol ; 132: 105161, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35508214

ABSTRACT

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.


Subject(s)
Cosmetics , Parabens , Cosmetics/chemistry , Cosmetics/toxicity , Parabens/chemistry , Parabens/toxicity , Preservatives, Pharmaceutical/toxicity , Reproduction , Risk Assessment/methods
6.
Food Chem ; 383: 132586, 2022 Jul 30.
Article in English | MEDLINE | ID: mdl-35247725

ABSTRACT

A novel water-based deep eutectic solvent was synthesized and used for the ultrasound-assisted liquid-liquid microextraction of parabens in edible oil and for their determination by high performance liquid chromatography. Herein, the water-based deep eutectic solvent was formulated at room temperature by tetrabutylammonium chloride as hydrogen bond acceptor and water as hydrogen bond donor at the molar ratio of 1:5. As component, water has the effect on tailoring the physicochemical properties of water-based deep eutectic solvent and assisting tetrabutylammonium chloride (hydrogen bond acceptor) capturing parabens (hydrogen bond donor) through in-situ deep eutectic solvent formation. The developed method has satisfactory linearity (1.5-500 µg/L), limits of detections (0.2-0.4 µg/L), precisions (RSDs ≤ 5.8%), and was fruitfully applied to detect parabens in edible oil with excellent recoveries (85.1-106.8%). The feature of the procedure lies in simplicity, low cost and high sensitivity, and this can be extended for the efficient separation of other hydrophobic compounds.


Subject(s)
Liquid Phase Microextraction , Deep Eutectic Solvents , Limit of Detection , Liquid Phase Microextraction/methods , Parabens , Solvents/chemistry , Water
7.
Environ Toxicol Pharmacol ; 92: 103856, 2022 May.
Article in English | MEDLINE | ID: mdl-35342011

ABSTRACT

Parabens are widely used as preservatives in pharmaceuticals, cosmetics, and food products. Ethylparaben (EP) and propylparaben (PP) are particularly preferred because of their bactericidal and fungicidal effects. Although generally described as safe compounds, many studies have reported that parabens have estrogenic and endocrine-disrupting properties. In the present study, the effects of EP and PP (50 mM, 100 mM and 200 mM) on Drosophila melanogaster development and fecundity were investigated. No differences were found in the pupation and maturation percentages in all concentrations of parabens (p > 0.05). However, it was found that the mean pupation and maturation times increased in all treatment groups (p < 0.05). A statistically significant decrease (p < 0.05) in the number of offspring of the 200 mM ethylparaben exposure group was observed. In all paraben groups, a significant reduction in mean fecundity was found compared to the control group (p < 0.05).


Subject(s)
Cosmetics , Parabens , Animals , Drosophila melanogaster , Fertility , Parabens/toxicity , Preservatives, Pharmaceutical/toxicity
8.
Ecotoxicol Environ Saf ; 230: 113124, 2022 Jan 15.
Article in English | MEDLINE | ID: mdl-34968799

ABSTRACT

OBJECTIVE: Parabens are commonly used as preservatives in foodstuffs, cosmetics, and pharmaceutical products. The widespread use of parabens has led to their leaking into the environment. Concerns about the safety of parabens have recently increased due to their potential endocrine-disrupting effects as an emerging contaminant. Thus, it is necessary to study the metabolism of parabens in vivo. METHODS: In this study, Drosophila melanogaster in males and females were exposed to ethylparaben (EP) concentration group (300 mg/L, 700 mg/L, and 1000 mg/L), and control group (0 mg/L) by the capillary feeding assay (CAFE). We quantified the activity of the detoxification-related carboxylesterase (CarE). The contents of EP metabolites in D. melanogaster, including p-hydroxybenzoic acid (PHBA), methylparaben (MP), and intact EP were carried out by high-performance liquid chromatography (HPLC). The regression model between EP metabolites (PHBA and MP) and CarE was developed using the Fourier series fitting method. RESULTS: The general level of EP metabolites (PHBA, MP, and intact EP) accumulation was accounted for 5.6-11.5% in D. melanogaster. As EP accumulated, the activity of CarE increased, and the activity of CarE in females was higher than males, which is inconsistent with the result of EP intake dose. Additionally, there were significant differences in the proportion of EP metabolites between female and male flies, and the results of sex comparison were different depending on the EP treated groups and EP metabolites. In general, PHBA of EP hydrolytic product and MP of EP transesterification product in D. melanogaster were 41.4-63.9% and 10.4-24.6%, respectively. In terms of the rest of the EP existed in intact form and ranged from 22.4% to 34.0%. Moreover, the EP metabolites in the conjugated form were higher than those in the free form. The regression model between EP metabolites and CarE was established, showing that the CarE activity can be used to estimate the content of PHBA and MP. CONCLUSION: The result indicates that the EP can accumulate in the body through food. Hydrolysis is the main metabolic pathway of EP in D. melanogaster, and transesterification is another metabolic pathway of EP. Additionally, the EP metabolites in flies mainly exist in conjugated form. Furthermore, the Fourier series fitting method model between EP metabolites and CarE, providing theoretical support to study the dose-effect relationship between metabolites of parabens and CarE. This study not only provides a mathematical basis for the safety evaluation of parabens, but also provides support for the further study of the toxicological effects of parabens.

9.
Environ Geochem Health ; 44(8): 2435-2449, 2022 Aug.
Article in English | MEDLINE | ID: mdl-34272621

ABSTRACT

Ethylparaben is used as an antifungal preservative. Although some countries have implemented regulations for human exposure to parabens, environmental regulations for ethylparaben have not been established. This study provides new toxicological data for ethylparaben, for which data regarding soil organisms were previously lacking. Although ethylparaben toxicity has been reported in other species, we present herein the first comprehensive study of its toxicity in soil organisms. We used 12 test species (Lycopersicon esculentum, Vigna radiata, Hordeum vulgare, Oryza sativa, Eisenia andrei, Folsomia candida, Lobella sokamensis, Caenorhabiditis elegans, Chlamydomonas reinhardtii, Chlorococcum infusionum, Chlorella sorokiniana, Chlorella vulgaris) from eight taxonomic groups for acute bioassays and nine test species (L. esculentum, V. radiata, H. vulgare, O. sativa, C. reinhardtii, C. infusionum, C. sorokiniana, and C. vulgaris) from five taxonomic groups for chronic bioassays. A suite of acute and chronic toxicity tests, using 21 soil species, was conducted to estimate EC50 values, which facilitated the construction of species sensitivity distributions (SSDs) and the calculation of protective concentrations (PCs). Acute and chronic PC95 values (protective concentration for 95% of species) for ethylparaben were estimated to be 14 and 5 mg/kg dry soil, respectively. To the best of our knowledge, this is the first study to evaluate the toxicity of ethylparaben to soil species and derive PCs for soil ecosystems based on SSDs. Therefore, the data presented in this study can be used as a basis for further investigations of paraben toxicity to the soil environment.


Subject(s)
Arthropods , Chlorella vulgaris , Soil Pollutants , Animals , Ecosystem , Humans , Parabens , Soil
10.
J Appl Toxicol ; 41(11): 1732-1746, 2021 11.
Article in English | MEDLINE | ID: mdl-34101200

ABSTRACT

Ethylparaben (EtP) and propylparaben (PrP) are common preservatives and well-known endocrine-disrupting chemicals. Studies have demonstrated that they can reduce female fertility, but the underlying mechanism, especially that on embryo implantation, is still poorly understood. Endometrial decidualization is a critical event for embryo implantation. In this study, we aimed to explore the effects of EtP/PrP on endometrial decidualization. Pregnant mice were dosed daily by oral gavage with EtP at 0, 400, 800 and 1600 mg/kg or with PrP at 0, 625, 1250 and 2500 mg/kg from Day 1 of pregnancy until sacrifice. The results showed that the rate of pregnant mice with impaired embryo implantation, whose number of implantation sites was less than 7, was significantly increased after exposure to 1600 mg/kg EtP or 2500 mg/kg PrP. Further study found that the expression of endometrial decidualization markers HOXA10, MMP9 and PR was significantly downregulated in 1600 mg/kg EtP group and 2500 mg/kg PrP group. Notably, serum oestrogen and progesterone levels were significantly increased, whereas the expression of uterine oestrogen receptor and progesterone receptor was decreased following 1600 mg/kg EtP or 2500 mg/kg PrP exposure. In the breeding test, fewer offspring were found after females were exposed to 1600 mg/kg EtP or 2500 mg/kg PrP in early pregnancy. This demonstrated that exposure to EtP/PrP interfered with embryo implantation by compromising endometrial decidualization in early-stage pregnant mice. Disorders of reproductive hormones and hormone receptor signals could be responsible for impaired decidualization. This study broadened the understanding on the biological safety of EtP and PrP.


Subject(s)
Embryo Implantation/drug effects , Endocrine Disruptors/toxicity , Endometrium/drug effects , Parabens/toxicity , Preservatives, Pharmaceutical/toxicity , Animals , Female , Mice , Pregnancy
11.
J Appl Toxicol ; 41(11): 1852-1862, 2021 11.
Article in English | MEDLINE | ID: mdl-33826164

ABSTRACT

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.


Subject(s)
Endocrine Disruptors/toxicity , Parabens/toxicity , Zebrafish , Animals , Larva/drug effects , Larva/growth & development , Zebrafish/growth & development
12.
Article in English | MEDLINE | ID: mdl-33922135

ABSTRACT

Previous human and animal studies have reported an association between endocrine-disrupting chemicals (EDCs) and anxiety/depression. This study aimed to determine how the concentrations of phthalate metabolites, bisphenol A, triclosan, and parabens in breast milk are associated with the risk of developing postpartum depression (PPD) in Korean mothers. We recruited 221 mothers who were receiving lactation coaching at breastfeeding clinics between July and September 2018. The breast milk samples were collected along with responses to the Edinburgh Postnatal Depression Scale. The multivariable logistic regression results revealed that the phthalate, bisphenol A, parabens, and triclosan levels in the breast milk were not significantly associated with the risk of PPD. This study was the first attempt to analyze the association between the levels of EDCs in breast milk and the risk of PPD. Considering that PPD is a condition that affects not only the women diagnosed with it, but also their children and families, the results of this study may have great relevance to populations in environmentally sensitive periods.


Subject(s)
Depression, Postpartum , Endocrine Disruptors , Phthalic Acids , Child , Depression, Postpartum/epidemiology , Endocrine Disruptors/analysis , Female , Humans , Milk, Human/chemistry , Mothers , Republic of Korea/epidemiology
13.
Exp Ther Med ; 21(4): 295, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33717238

ABSTRACT

The aim of the present study was to explore the etiology of subconjunctival fibrosis (SCF) induced by ethylparaben, the most prevalent preservative in Chinese eye drops. Ethylparaben was administered to the left eyes of male Sprague-Dawley rats in the experimental group twice daily for 1 month, whereas the control group received PBS. Experimental group rats displayed a mild promotion in density of fibroblasts and a tighter deposition of collagen in the bulbar subepithelial connective tissue compared with the control group. Furthermore, the present findings revealed that extracellular matrix expression was promoted in murine bulbar conjunctival tissues in the experimental group. In primary conjunctival fibroblasts, expression of ECM triggered by ethylparaben was suppressed by XAV-939. Furthermore, stimulation of the Wnt/ß-catenin axis triggered by ethylparaben was impaired by XAV-939. In conclusion, SCF triggered by ethylparaben results from extra ECM generation of conjunctival fibroblasts via the Wnt/ß-catenin axis.

14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-862491

ABSTRACT

Objective To improve the quality control of Dilong Shenmai oral liquid. Methods TLC was used for the qualitative identification of Astragali Radix, Ophiopogonis Radix and Schisandrae Chinensis Fructus in Dilong Shenmai oral liquid. HPLC was used to determine the contents of schisandrin and ethylparaben in the preparation. Wondasil C18 column (250 mm×4.6 mm, 5 μm) was used with acetonitrile-water as the mobile phase at the flow rate of 1.0 ml/min for gradient elution. The detection wavelength was set at 254 nm, and column temperature was 30 ℃. Results TLC spots were clear and well-separated without negative interference. The linear ranges of schisandrin and ethylparaben were 5.81−58.06 μg/ml (r=0.999 9) and 25.29−252.94 μg/ml (r=0.999 9). The average recoveries were 99.35% (RSD=1.02%) and 99.72% (RSD=0.76%). Conclusion This method is simple, quick and accurate. It can be used for effective quality control of Dilong Shenmai oral liquid.

15.
Environ Toxicol Pharmacol ; 80: 103495, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32949725

ABSTRACT

Parabens are esters of p-hydroxybenzoic acid, including methylparaben (MP), ethylparaben (EP), propylparaben (PP), and the like. This substance has estrogenic and antiandrogenic effects, and a putative role in promoting cancer through endocrine disruption. By exposing Drosophila melanogaster to different concentrations of EP (300 mg/L, 700 mg/L, and 1000 mg/L), we investigated the effect of EP on the growth and development of D. melanogaster before emergence. We found that EP prolonged the development cycle of D. melanogaster, and changed the relative expression levels of Met, Gce, EcR, Kr-h1, and Br. In addition, EP reduced the titer of juvenile hormone Ⅲ (JH Ⅲ) and 20-hydroxyecdysone (20E), and delayed the peak of hormone secretion. This study provided a more objective and thorough assessment of safety for the parabens.


Subject(s)
Drosophila melanogaster/drug effects , Life Cycle Stages/drug effects , Parabens/toxicity , Animals , Drosophila Proteins/genetics , Drosophila melanogaster/growth & development , Ecdysterone/metabolism , Female , Gene Expression Regulation, Developmental/drug effects , Male , Sesquiterpenes/metabolism
16.
Biomed Pharmacother ; 128: 110250, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32480218

ABSTRACT

Propylparaben, a commonly used antimicrobial preservative, has been reported as an anticonvulsant agent targeting neuronal Na+ channels (NaV). However, the specific features of the NaV channel inhibition by this agent have so far not been extensively studied. Moreover, it is still unclear if it shares this pharmacological activity with other parabens. Here, we fully characterized the mechanism of action of the inhibitory effect that propylparaben and benzylparaben induce on human NaV 1.2 channel isoform (hNaV1.2). We established a first approach to know the parabens structural determinants for this channel inhibition. The parabens effects on hNaV1.2 channel mediated currents were recorded using the patch-clamp whole-cell configuration on hNaV1.2 stably transfected HEK293 cells. Propylparaben induced a typical state-dependent inhibition on hNaV1.2 channel carried current, characterized by a left-shift in the steady-state inactivation curve, a prolongation in the time needed for recovery from fast inactivation and a frequency-dependent blocking behavior. The state-dependent inhibition is increased for butylparaben and benzylparaben and diminished for methylparaben, ethylparaben and p-hydroxybenzoic acid (the major metabolite of parabens hydrolysis). Particularly, butylparaben and benzylparaben shift the steady-state inactivation curve 2- and 3-times more than propylparaben, respectively. Parabens are blockers of hNaV1.2 channels, sharing the mechanism of action of most of sodium channel blocking antiseizure drugs. The potency of this inhibition increases with the size of the lipophilic alcoholic residue of the ester group. These results provide a basis for rational drug design directed to generate new potential anticonvulsant agents.


Subject(s)
NAV1.2 Voltage-Gated Sodium Channel/drug effects , Parabens/pharmacology , Voltage-Gated Sodium Channel Blockers/pharmacology , Dose-Response Relationship, Drug , HEK293 Cells , Humans , Membrane Potentials , Molecular Structure , NAV1.2 Voltage-Gated Sodium Channel/genetics , NAV1.2 Voltage-Gated Sodium Channel/metabolism , Parabens/chemistry , Structure-Activity Relationship , Voltage-Gated Sodium Channel Blockers/chemistry
17.
Exp Eye Res ; 196: 108057, 2020 07.
Article in English | MEDLINE | ID: mdl-32387382

ABSTRACT

Recently, we discovered that the cosmetic preservatives, benzalkonium chloride and formaldehyde, are especially toxic to human meibomian gland epithelial cells (HMGECs). Exposure to these agents, at concentrations approved for human use, leads within hours to cellular atrophy and death. We hypothesize that these effects are not unique, and that other cosmetic preservatives also exert adverse effects on HMGECs. Such compounds include parabens, phenoxyethanol and chlorphenesin, which have been reported to be toxic to corneal and conjunctival epithelial cells, the liver and kidney, as well as to irritate the eye. To test our hypothesis, we examined the influence of parabens, phenoxyethanol and chlorphenesin on the morphology, signaling, survival, proliferation and lipid expression of immortalized (I) HMGECs. These cells were cultured under proliferating or differentiating conditions with varying concentrations of methylparaben, ethylparaben, phenoxyethanol and chlorphenesin for up to 5 days. We monitored the signaling ability, appearance, number and neutral lipid content of the IHMGECs, as well as their lysosome accumulation. Our findings show that a 30-min exposure of IHMGECs to these preservatives results in a significant reduction in the activity of the Akt pathway. This effect is dose-dependent and occurs at concentrations equal to (chlorphenesin) and less than (all others) those dosages approved for human use. Further, a 24-h treatment of the IHMGECs with concentrations of methylparaben, ethylparaben, phenoxyethanol and chlorphenesin close to, or at, the approved human dose induces cellular atrophy and death. At all concentrations tested, no preservative stimulated IHMGEC proliferation. Of particular interest, it was not possible to evaluate the influence of these preservatives, at close to human approved dosages, on IHMGEC differentiation, because the cells did not survive the treatment. In summary, our results support our hypothesis and show that methylparaben, ethylparaben, phenoxyethanol and chlorphenesin are toxic to IHMGECs.


Subject(s)
Chlorphenesin/toxicity , Cosmetics , Epithelial Cells/drug effects , Ethylene Glycols/toxicity , Meibomian Glands/drug effects , Parabens/toxicity , Preservatives, Pharmaceutical/toxicity , Cell Count , Cell Differentiation , Cell Proliferation , Cell Survival , Cells, Cultured , Dose-Response Relationship, Drug , Electrophoresis, Polyacrylamide Gel , Epithelial Cells/metabolism , Humans , Immunoblotting , Lipid Metabolism/physiology , Lysosomes/metabolism , Meibomian Glands/metabolism , Proto-Oncogene Proteins c-akt/metabolism
18.
Anim Cells Syst (Seoul) ; 24(1): 34-43, 2020.
Article in English | MEDLINE | ID: mdl-32158614

ABSTRACT

Parabens are generally used as preservatives in foods, pharmaceuticals, and various other commercial products. Among them, ethylparaben has weaker estrogenic characteristics than endogenous estrogen. However, growing evidence indicates that ethylparaben has an adverse effect on various human tissues. Here, we investigated whether ethylparaben induces cell death by affecting cell viability, cell proliferation, cell cycle, and apoptosis using the human placenta cell line BeWo. Ethylparaben significantly decreased cell viability in a dose-dependent manner. It caused cell cycle arrest at sub-G1 by reducing the expression of cyclin D1, whereas it decreased the cell proportion at the G0/G1 and S phases. Furthermore, we verified that ethylparaben induces apoptotic cell death by enhancing the activity of Caspase-3. Taken together, our results suggest that ethylparaben exerts cytotoxic effects in human placental BeWo cells via cell cycle arrest and apoptotic pathways.

19.
Int J Pharm ; 578: 119115, 2020 Mar 30.
Article in English | MEDLINE | ID: mdl-32045690

ABSTRACT

Alzheimer's disease (AD) is a common and severe brain disease with a high mortality among the elders, but no highly efficient medications are currently available. For example, timosaponin BII, an efficient anti-AD agent, has low oral bioavailability. Here, timosaponin BII was formulated in a temperature/ion-sensitive in situ hydrogel (ISG) that was well transformed into gels in the nasal environment. Timosaponin BII protected the PC12 cells injured by lipopolysaccharides (LPS) by decreasing TNF-α and IL-1ß and stabilizing F-actin. Timosaponin BII ISGs were intranasally administered to the mice every day for 38 days. On Day 36, LPS was injected to the mice to establish an AD model. Morris water maze experiments showed that the number of the animals that were able to cross the platform returned to normal and the total distance over which the animals moved in the open field also increased, which demonstrated that the spatial memory and spontaneous behavior were improved after treatment compared to the model. Moreover, an AD improver, inducible nitric oxide synthase (iNOS) in the brain, was reduced after treatment. High brain targeting effect of timosaponin BII ISGs was confirmed by in vivo fluorescence imaging. The nasal timosaponin BII dually sensitive ISGs can serve as a promising medication for local prevention of AD.


Subject(s)
Alzheimer Disease/chemically induced , Alzheimer Disease/drug therapy , Hydrogels/administration & dosage , Lipopolysaccharides/pharmacology , Saponins/administration & dosage , Steroids/administration & dosage , Administration, Intranasal , Alzheimer Disease/metabolism , Animals , Anura , Cell Line, Tumor , Female , Interleukin-1beta/metabolism , Male , Mice , Mice, Inbred C57BL , Nitric Oxide Synthase Type II/metabolism , Nose/drug effects , PC12 Cells , Rabbits , Rats , Sheep , Tumor Necrosis Factor-alpha/metabolism
20.
Trends Environ Anal Chem ; 28: e00103, 2020 Dec.
Article in English | MEDLINE | ID: mdl-38620429

ABSTRACT

Humans are nowadays exposed to numerous chemicals in our day-to-day life, including parabens, UV filters, phosphorous flame retardants/plasticizers, bisphenols, phthalates and alternative plasticizers, which can have different adverse effects to human health. Estimating human's exposure to these potentially harmful substances is, therefore, of paramount importance. Human biomonitoring (HBM) is the existing approach to assess exposure to environmental contaminants, which relies on the analysis of specific human biomarkers (parent compounds and/or their metabolic products) in biological matrices from individuals. The main drawback is its implementation, which involves complex cohort studies. A novel approach, wastewater-based epidemiology (WBE), involves estimating exposure from the analysis of biomarkers in sewage (a pooled urine and feces sample of an entire population). One of the key challenges of WBE is the selection of biomarkers which are specific to human metabolism, excreted in sufficient amounts, and stable in sewage. So far, literature data on potential biomarkers for estimating exposure to these chemicals are scattered over numerous pharmacokinetic and HBM studies. Hence, this review provides a list of potential biomarkers of exposure to more than 30 widely used chemicals and report on their urinary excretion rates. Furthermore, the potential and challenges of WBE in this particular field is discussed through the review of pioneer WBE studies, which for the first time explored applicability of this novel approach to assess human exposure to environmental contaminants. In the future, WBE could be potentially applied as an "early warning system", which could promptly identify communities with the highest exposure to environmental contaminants.

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