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1.
Reprod Toxicol ; 127: 108612, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38782143

ABSTRACT

The increasing global prevalence of gestational diabetes mellitus (GDM) has been hypothesized to be associated with maternal exposure to environmental chemicals. Here, among 420 women participating in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study, we examined associations between GDM and second trimester blood or urine concentrations of endocrine disrupting chemicals (EDCs): bisphenol-A (BPA), bisphenol-S (BPS), twelve phthalate metabolites, eight perfluoroalkyl acids (PFAAs), and eleven trace elements. Fifteen (3.57%) of the women were diagnosed with GDM, and associations between the environmental chemical exposures and GDM diagnosis were examined using multiple logistic and LASSO regression analyses in single- and multi-chemical exposure models, respectively. In single chemical exposure models, BPA and mercury were associated with increased odds of GDM, while a significant inverse association was observed for zinc. Double-LASSO regression analysis selected mercury (AOR: 1.51, CI: 1.12-2.02), zinc (AOR: 0.017, CI: 0.0005-0.56), and perfluoroundecanoic acid (PFUnA), a PFAAs, (AOR: 0.43, CI: 0.19-0.94) as the best predictors of GDM. The combined data for this Canadian cohort suggest that second trimester blood mercury was a robust predictor of GDM diagnosis, whereas blood zinc and PFUnA were protective factors. Research into mechanisms that underlie the associations between mercury, zinc, PFUnA, and the development of GDM is needed.


Subject(s)
Benzhydryl Compounds , Diabetes, Gestational , Endocrine Disruptors , Environmental Pollutants , Fluorocarbons , Maternal Exposure , Phenols , Phthalic Acids , Female , Humans , Pregnancy , Fluorocarbons/blood , Diabetes, Gestational/epidemiology , Diabetes, Gestational/blood , Phenols/blood , Phenols/urine , Adult , Benzhydryl Compounds/blood , Benzhydryl Compounds/urine , Phthalic Acids/urine , Phthalic Acids/blood , Endocrine Disruptors/blood , Endocrine Disruptors/urine , Maternal Exposure/adverse effects , Environmental Pollutants/blood , Cohort Studies , Trace Elements/blood , Trace Elements/urine , Alkanesulfonic Acids/blood , Young Adult , Sulfones
2.
Food Chem Toxicol ; 189: 114750, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38777166

ABSTRACT

This study aims to investigate the associations of bisphenols with sex and thyroid hormones in cord blood among newborns. Four bisphenols, three hormones related to gonadal function, and four parameters related to thyroid function were measured in umbilical cord blood in 378 mother-newborn pairs. Multivariable linear regression, quantile-based g-computation (QGC), and Bayesian kernel machine regression were used. In the multivariable linear regression, bisphenol A (BPA) was associated with increased testosterone (TT) (regression coefficient, ß = 0.049, 95% confidence interval, CI: 0.013,0.085; p = 0.007) and free tri-iodothyronine (FT3) levels (ß = 0.019, 95% CI: 0.003, 0.035; p = 0.023), and decreased thyroid peroxidase antibody (TPOAb) (ß = -0.053, 95% CI: 0.098, -0.008; p = 0.021). Consistently associations were observed in males, except TT, which was observed in females, and bisphenol AF (BPAF) was associated with decreased follicle-stimulating hormone (FSH) in females. These associations were also observed in a mixture of bisphenols. Moreover, we observed maternal prepregnancy body mass index (BMI) and delivery mode disparity in the relationship between bisphenols and sex and thyroid hormones. This study suggests that bisphenols may exert effects on sex and thyroid hormones in newborns, the effect may vary with sex differences, maternal prepregnancy BMI, and delivery mode.


Subject(s)
Benzhydryl Compounds , Fetal Blood , Phenols , Thyroid Hormones , Humans , Phenols/blood , Fetal Blood/chemistry , Female , Male , Infant, Newborn , Benzhydryl Compounds/blood , Thyroid Hormones/blood , Adult , Pregnancy , Testosterone/blood , Endocrine Disruptors/blood , Triiodothyronine/blood
3.
Front Public Health ; 12: 1351786, 2024.
Article in English | MEDLINE | ID: mdl-38665245

ABSTRACT

Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary's Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables (ß = 0.003, p < 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 µg/g creatinine vs. 1.71 µg/g creatinine [p < 0.05]; cord blood BPA, 1.96 µg/L vs. -0.86 µg/L [p < 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR.


Subject(s)
Benzhydryl Compounds , Endocrine Disruptors , Fetal Blood , Fetal Growth Retardation , Maternal Exposure , Phenols , Humans , Female , Endocrine Disruptors/adverse effects , Endocrine Disruptors/blood , Endocrine Disruptors/urine , Prospective Studies , Pregnancy , Fetal Growth Retardation/chemically induced , Adult , Benzhydryl Compounds/adverse effects , Benzhydryl Compounds/urine , Benzhydryl Compounds/blood , Phenols/urine , Phenols/adverse effects , Phenols/blood , Maternal Exposure/adverse effects , Fetal Blood/chemistry , Fluorocarbons/blood , Fluorocarbons/adverse effects , Phthalic Acids/urine , Phthalic Acids/adverse effects , Caprylates/blood , Caprylates/adverse effects , Placental Insufficiency , Republic of Korea/epidemiology , Seoul/epidemiology
4.
Chemosphere ; 357: 142082, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38642776

ABSTRACT

Studies have shown that bisphenol S (BPS) is mainly present as its conjugated metabolites in human blood. However, the distribution of conjugated BPS metabolites in different human blood matrices has not been characterized. In this study, paired human serum and whole blood samples (n = 79) were collected from Chinese participants, and were measured for the occurrence of BPS and 4 BPS metabolites. BPS was detectable in 49% of human serum (

Subject(s)
Phenols , Sulfones , Humans , Phenols/blood , Phenols/metabolism , Sulfones/blood , Sulfones/metabolism , Male , Female , Environmental Pollutants/blood , Environmental Pollutants/metabolism , Adult , Glucuronides/blood , Glucuronides/metabolism , Sulfuric Acid Esters/blood , Middle Aged
5.
J Perinatol ; 44(7): 1029-1034, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38499756

ABSTRACT

OBJECTIVE: In this study, we aimed to evaluate BPA levels in the maternal serum and amniotic fluid of patients diagnosed with NTD. In addition, we wanted to investigate the relationship between neurodevelopmental defects, such as neural tube defects (NTD), and BPA levels. STUDY DESIGN: This prospective observational study was carried out at Bursa Yüksek Ihtisas Training and Research Hospital between April 15, 2021, and April 15, 2022. The study consisted of 92 patients between the ages of 18-45 who had an amniocentesis at 15-22 weeks of gestation. The patients were divided into two groups according to the indications of amniocentesis. Group 1 contained the patients with abnormal maternal serum screening results or cell-free DNA results and abnormal ultrasonography findings (45 patients). Group 2 contained the patients with a pre-diagnosis of NTD (47 patients). The first 5 cc fluids and maternal serum samples taken during the amniocentesis procedure of all patients were delivered to the biochemistry laboratory. The BPA values between groups were compared. RESULTS: A statistically significant difference was found between the two groups in terms of amniotic fluid BPA levels (36.66 (19.00:82.00) and 39.62 (19.02-73.87)) and maternal blood BPA levels (22.26 (12.60-228) and 47.81 (12.89-228.39)). In cases with NTD, amniotic fluid BPA levels and maternal blood BPA levels were significantly higher than the control group. When AUC values were compared, the AFP numerical value was higher than the amniotic fluid and maternal blood BPA levels. CONCLUSION: Plastic, which is indispensable for modern life, may negatively affect fetal development in intrauterine life. The data in this study says that high maternal blood BPA may be associated with NTD.


Subject(s)
Amniocentesis , Amniotic Fluid , Benzhydryl Compounds , Neural Tube Defects , Phenols , Humans , Phenols/blood , Female , Benzhydryl Compounds/blood , Prospective Studies , Pregnancy , Amniotic Fluid/chemistry , Adult , Neural Tube Defects/diagnosis , Young Adult , Adolescent , Middle Aged , Gestational Age
6.
Front Public Health ; 12: 1196248, 2024.
Article in English | MEDLINE | ID: mdl-38379678

ABSTRACT

Background: Bisphenol A (BPA) is an oil-derived, large-market volume chemical with endocrine disrupting properties and reproductive toxicity. Moreover, BPA is frequently used in food contact materials, has been extensively researched recently, and widespread exposure in the general population has been reported worldwide. However, national information on BPA levels in general Chinese people is lacking. Methods: This study collected and analyzed 145 (104 in urine and 41 in serum) research articles published between 2004 and 2021 to reflect the BPA internal exposure levels in Chinese populations. The Monte Carlo simulation method is employed to analyze and estimate the data in order to rectify the deviation caused by a skewed distribution. Results: Data on BPA concentrations in urine and serum were collected from 2006 to 2019 and 2004 to 2019, respectively. Urinary BPA concentrations did not vary significantly until 2017, with the highest concentration occurring from 2018 to 2019 (2.90 ng/mL). The serum BPA concentration decreased to the nadir of 1.07 ng/mL in 2011 and gradually increased to 2.54 ng/mL. Nationally, 18 provinces were studied, with Guangdong (3.50 ng/mL), Zhejiang (2.57 ng/mL), and Fujian (2.15 ng/mL) having the highest urine BPA levels. Serum BPA was investigated in 15 provinces; Jiangsu (9.14 ng/mL) and Shandong (5.80 ng/mL) were relatively high. The results also indicated that males' urine and serum BPA levels were higher than females, while the BPA levels in children were also higher than in adults (p < 0.001). Furthermore, the volume of garbage disposal (r = 0.39, p < 0.05), household sewage (r = 0.34, p < 0.05), and waste incineration content (r = 0.35, p < 0.05) exhibited a strong positive connection with urine BPA levels in Chinese individuals. Conclusion: Despite using a data consolidation approach, our study found that the Chinese population was exposed to significant amounts of BPA, and males having a higher level than females. Besides, the levels of BPA exposure are influenced by the volume of garbage disposal, household sewage, and waste incineration content.


Subject(s)
Benzhydryl Compounds , East Asian People , Phenols , Sewage , Adult , Child , Female , Humans , Male , Benzhydryl Compounds/blood , Benzhydryl Compounds/urine , China , Phenols/blood , Phenols/urine , Risk Factors
7.
Reprod Sci ; 31(5): 1323-1331, 2024 May.
Article in English | MEDLINE | ID: mdl-38212582

ABSTRACT

This study investigated the association of blood and semen Bisphenol A (BPA) levels of the male partner on the reproductive outcome in intracytoplasmic sperm injection (ICSI) treatment cycles. For this prospective study (ClinicalTrials.gov identifier: NCT02703584), blood and semen samples of the male partner of the 75 women who had ICSI were analyzed. The study group consisted of men who had ICSI for male factor infertility other than azoospermia, while men with normal spermiogram whose partners underwent ICSI due to tubal factor infertility were taken as the study group. Habitual consumption of drinking water from plastic carboys/bottles (PBW) at home was also questioned in both groups as it was considered as chronic BPA exposure. The association of ICSI outcome with blood BPA (bBPA) and semen BPA (sBPA) levels was analyzed in both groups. No significant correlation was found between sperm parameters and bBPA levels in both groups. A negative correlation was found between sBPA levels and total sperm count and progressive sperm motility in men who consumed PBW. Embryo development arrest was found to be significantly higher in patients who have high sBPA levels. Although sBPA levels were not different in PBW consumers, bBPA levels were found to be significantly lower in those who consumed tap water (TW) than those who used PBW. Elevated bBPA were associated with a significant decrease in clinical pregnancy rate. Considering the widespread human exposure to BPA, the effect of BPA on the male reproductive system needs to be further examined.


Subject(s)
Benzhydryl Compounds , Phenols , Semen , Sperm Injections, Intracytoplasmic , Humans , Phenols/blood , Benzhydryl Compounds/blood , Benzhydryl Compounds/adverse effects , Male , Female , Adult , Pregnancy , Prospective Studies , Semen/chemistry , Infertility, Male/blood , Infertility, Male/therapy , Pregnancy Rate , Treatment Outcome , Sperm Motility/drug effects , Sperm Count
8.
Biochem Pharmacol ; 197: 114889, 2022 03.
Article in English | MEDLINE | ID: mdl-34979091

ABSTRACT

Bisphenol-A (BPA), an estrogenic endocrine disrupting chemical, significantly impacts numerous diseases and abnormalities in mammals. Estrogens are known to play an important role in the biology of the prostate; however, little is known about the role of bisphenols in the etiology of prostate pathologies, including benign prostate hyperplasia (BPH) and associated lower urinary tract dysfunction (LUTD). Bisphenol-F (BPF) and bisphenol-S (BPS) are analogs often used as substitutes for BPA; they are both reported to have in vitro and in vivo estrogenic effects similar to or more potent than BPA. The objective of this study was to assess the role of these bisphenols in the development of LUTD in adult male mice. In adult mice exposed to BPA, BPS or BPF, we examined urinary tract histopathology and physiological events associated with urinary dysfunction. Mice treated with bisphenols displayed increased bladder (p < 0.005) and prostate (p < 0.0001) mass, and there was an increased number of prostatic ducts in the prostatic urethra (p < 0.05) and decreased size of the urethra lumen (p < 0.05) compared to negative controls. After two months of bisphenol exposure, mice displayed notable differences in cystometric tracings compared to controls, consistent with LUTD. Treatment of male mice with all bisphenols also induced voiding dysfunction manifested by detrusor instability and histologic changes in the prostatic urethra of male rodents, consistent with LUTD. Our results implicate BPA and its replacements in the development and progression LUTD in mice and provide insights into the development and progression of BPH/LUTS in men.


Subject(s)
Benzhydryl Compounds/toxicity , Estrogens, Non-Steroidal/toxicity , Phenols/toxicity , Prostatic Hyperplasia/chemically induced , Urologic Diseases/chemically induced , Animals , Benzhydryl Compounds/blood , Benzhydryl Compounds/chemistry , Estrogens, Non-Steroidal/blood , Estrogens, Non-Steroidal/chemistry , Male , Mice , Mice, Inbred C57BL , Phenols/blood , Phenols/chemistry , Prostatic Hyperplasia/blood , Prostatic Hyperplasia/pathology , Urologic Diseases/blood , Urologic Diseases/pathology
9.
Toxicology ; 465: 153011, 2022 01 15.
Article in English | MEDLINE | ID: mdl-34715266

ABSTRACT

Endocrine-disrupting chemicals (EDCs) might increase the risk of childhood diseases by disrupting hormone-mediated processes that are critical for growth and development during childhood, however, the association among the exposure level of EDCs such as Nonylphenol (NP), Bisphenol A (BPA), Dimethyl phthalate (DMP) in children and environmental risk factors, as well as hepatic function has not been elaborated. This study aimed to discuss this interesting relationship among NP, BPA, DMP concentrations in serum, environmental risk factors, hepatic function of 5- to 14-year-old children in industrial zone, residential zone and suburb in northern district of Guizhou Province, China. In Zunyi city, 1006 children participated in cross-sectional health assessments from July to August 2018, and their parents completed identical questionnaires on the environmental risk factors of EDCs exposure to mothers and children. Serum NP, BPA and DMP concentrations were measured by high performance liquid chromatography (HPLC). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT, total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) were detected with automatic biochemical analyzer. The median concentrations of serum NP, BPA, and DMP in the participants were 45.85 ng/mL, 26.31 ng/mL and 31.62 ng/mL, respectively, which were higher than the environmental concentration limits of the U.S. National Environmental Protection Agency (EPA). Hair gels used during pregnancy, types of domestic drinking water, nail polish and cosmetics used by children were significantly positive correlated with serum NP concentration (P < 0.05). Gender, feeding pattern, plastic water cup used during pregnancy, hair spray and perfume use for children, duration of children birth, materials for baby bottle or cup and ways to plastic products were significantly positively correlated with serum BPA concentration (P < 0.05). Gender, perms used during pregnancy, hair spray and perfume use for children, using plastic lunch box during pregnancy, duration of children birth, exposure to pesticides, parents' occupations were significantly positively correlated with serum DMP concentrations (P < 0.05). Serum NP (ß = 0.296, P = 0.036) and DMP (ß = 0.316, P = 0.026) concentrations and TBIL level were significantly positively correlated. Serum NP concentration and the levels of IBIL (ß = 0.382, P = 0.006) are significantly positively correlated. Cosmetics used during pregnancy significantly increased AST level (ß = 2.641, P = 0.021). There was a positive correlation between the frequency of hair spray and perfume use for children and the AST (ß = 4.241, P = 0.022). NP, BPA and DMP, which were commonly detected in the serum of children aged 5-14 years old in Zunyi City, Northern Guizhou Province, China, were closely related to the environmental risk factors of exposure environment during pregnancy, infancy and school age. Exposure to NP, BPA and DMP would have negative effects on hepatic function, and these effects showed differences in gender and geographical location. Notably,The relationships were more evident in girls than in boys.


Subject(s)
Chemical and Drug Induced Liver Injury/epidemiology , Endocrine Disruptors/blood , Environmental Exposure , Environmental Pollutants/blood , Liver/drug effects , Adolescent , Age Factors , Benzhydryl Compounds/blood , Benzhydryl Compounds/toxicity , Body Burden , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/metabolism , Child , Child, Preschool , China/epidemiology , Cross-Sectional Studies , Endocrine Disruptors/adverse effects , Environmental Exposure/adverse effects , Environmental Monitoring , Environmental Pollutants/adverse effects , Female , Humans , Liver/metabolism , Liver/pathology , Male , Phenols/adverse effects , Phenols/blood , Phenols/toxicity , Phthalic Acids/blood , Phthalic Acids/toxicity , Residence Characteristics , Risk Assessment , Risk Factors , Sex Factors
10.
Biomolecules ; 11(9)2021 09 17.
Article in English | MEDLINE | ID: mdl-34572587

ABSTRACT

Bisphenol A (BPA), also known as 2,2,-bis(4-hydroxyphenyl) propane, is a common component of plastics worldwide. However, it has been shown to act as an endocrine disruptor with some hormonal functions. Furthermore, high levels of BPA have been related to the development of cardiovascular events and the activation of carcinogenesis pathways. Patients with chronic kidney disease (CKD) have higher serum concentrations of BPA due to their impaired renal function. This situation is aggravated in CKD patients requiring dialysis, because the BPA content of dialysis devices (such as, for example, the filters) is added to the lack of excretion. In addition to the development of BPA-free dialysis filters, some techniques can contribute to the reduction of BPA levels in these patients. The aim of this review is to illustrate the impact of BPA on dialysis patients and suggest some strategies to reduce its inherent risks.


Subject(s)
Benzhydryl Compounds/adverse effects , Phenols/adverse effects , Renal Dialysis , Benzhydryl Compounds/blood , Benzhydryl Compounds/chemistry , Blood Vessels/pathology , Filtration/instrumentation , Humans , Kidney/pathology , Phenols/blood , Phenols/chemistry , Plastics/adverse effects , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/pathology
11.
Front Endocrinol (Lausanne) ; 12: 694669, 2021.
Article in English | MEDLINE | ID: mdl-34335471

ABSTRACT

Objective: to explore the association of plasma concentrations of bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) with unilateral cryptorchidism. In addition, to analyze selected demographic and intraoperative characteristics. Design: Retrospective analysis to determine plasma concentrations of total BPA, BPS and BPF using gas chromatography - mass spectrometry (GC-MS) among prepubertal boys with cryptorchidism and prebupertal male control subjects. During operation, the size, turgor and location of the cryptorchid testes were assessed. Main Outcome Measure: Plasma concentrations of total BPA, BPS and BPF. Results: In children with cryptorchidism, plasma levels of BPA, BPS and BPF were significantly higher compared to the control subjects. For BPA, it was: median value: 9.95 ng/mL vs. 5.54 ng/mL, p<0.05. For BPS, it was: median value: 3.93 ng/mL vs. 1.45 ng/mL, p<0.001. For BPF, it was: median value: 3.56 ng/mL vs. 1.83 ng/mL, p<0.05. In cryptorchid group, BPA was detected in 61.4% samples, BPS in 19.3% and BPF in 19.3%. All the three bisphenols were detected in plasma samples of both the healthy subjects and the study cohort. In the latter group, we found significant higher levels of BPA in boys from urban areas. We found a weak positive correlation between the levels of BPS and BPF and reduced turgor of the testes. Furthermore, results showed weak positive correlations between BPA and BPS levels and the age of the children as well as between BPS and BPF concentrations and the place of residence. Conclusions: Results provide a first characterization of prepubertal boys suffering from cryptorchidism and exposed to different kind of bisphenols. Our study suggests that cryptorchid boys are widely exposed to BPA and, to a lesser extent, also to its alternatives, such as BPS and BPF.


Subject(s)
Benzhydryl Compounds/blood , Cryptorchidism/blood , Phenols/blood , Sulfones/blood , Case-Control Studies , Child, Preschool , Cryptorchidism/epidemiology , Cryptorchidism/etiology , Humans , Infant , Infant, Newborn , Male , Poland/epidemiology , Retrospective Studies , Risk Factors , Urban Population/statistics & numerical data
12.
Biomolecules ; 11(7)2021 07 16.
Article in English | MEDLINE | ID: mdl-34356670

ABSTRACT

Bisphenol A (BPA) is a compound that is especially widespread in most commonly used objects due to its multiple uses in the plastic industry. However, several data support the need to restrict its use. In recent years, new implications of BPA on the renal system have been discovered, which denotes the need to expand studies in patients. To this end, a systematic review and a meta-analysis was performed to explore existing literature that examines the BPA-kidney disease paradigm and to determine what and how future studies will need to be carried out. Our systematic review revealed that only few relevant publications have focused on the problem. However, the subsequent meta-analysis revealed that high blood concentrations of BPA could be a factor in developing kidney disease, at least in people with previous pathologies such as diabetes or hypertension. Furthermore, BPA could also represent a risk factor in healthy people whose urinary excretion is higher. Finally, the data analyzed from the NHANES 03-16 cohort provided new evidence on the possible involvement of BPA in kidney disease. Therefore, our results underline the need to carry out a thorough and methodologically homogeneous study, delving into the relationship between urinary and blood BPA, glomerular filtration rate, and urine albumin-to-creatinine ratio, preferably in population groups at risk, and subsequently in the general population, to solve this relevant conundrum with critical potential implications in Public Health.


Subject(s)
Benzhydryl Compounds/toxicity , Kidney Diseases/chemically induced , Phenols/toxicity , Benzhydryl Compounds/blood , Benzhydryl Compounds/urine , Environmental Exposure/adverse effects , Female , Humans , Male , Nutrition Surveys , Phenols/blood , Phenols/urine
13.
Environ Health ; 20(1): 88, 2021 08 16.
Article in English | MEDLINE | ID: mdl-34399780

ABSTRACT

BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor that it is present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident breast and prostate cancer in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: We designed a case-cohort study within the EPIC-Spain cohort. Study population consisted on 4812 participants from 4 EPIC-Spain centers (547 breast cancer cases, 575 prostate cancer cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Borgan II weighted Cox regression was used to estimate hazard ratios. RESULTS: Median follow-up time in our study was 16.9 years. BPA geometric mean serum values of cases and sub-cohort were 1.12 ng/ml vs 1.10 ng/ml respectively for breast cancer and 1.33 ng/ml vs 1.29 ng/ml respectively for prostate cancer. When categorizing BPA into tertiles, a 40% increase in risk of prostate cancer for tertile 1 (p = 0.022), 37% increase for tertile 2 (p = 0.034) and 31% increase for tertile 3 (p = 0.072) was observed with respect to values bellow the limit of detection. No significant association was observed between BPA levels and breast cancer risk. CONCLUSIONS: We found a similar percentage of detection of BPA among cases and sub-cohort from our population, and no association with breast cancer risk was observed. However, we found a higher risk of prostate cancer for the increase in serum BPA levels. Further investigation is needed to understand the influence of BPA in prostate cancer risk.


Subject(s)
Benzhydryl Compounds/blood , Breast Neoplasms/epidemiology , Endocrine Disruptors/blood , Environmental Exposure/analysis , Environmental Pollutants/blood , Phenols/blood , Prostatic Neoplasms/epidemiology , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Risk , Spain/epidemiology
14.
FASEB J ; 35(7): e21697, 2021 07.
Article in English | MEDLINE | ID: mdl-34085740

ABSTRACT

The relevance of environmental triggers in Crohn's disease remains poorly explored, despite the well-known association between industrialization and disease onset/progression. We have aimed at evaluating the influence of endocrine disrupting chemicals in CD patients. We performed a prospective observational study on consecutive patients diagnosed of CD. Serum levels of endocrine disruptors, short-chain fatty acids, tryptophan and cytokines were measured. Bacterial-DNA and serum endotoxin levels were also evaluated. Gene expression of ER-α, ER-ß and GPER was measured in PBMCs. All patients were genotyped for NOD2 and ATG16L1 polymorphisms. A series of 200 CD patients (140 in remission, 60 with active disease) was included in the study. Bisphenol A was significantly higher in patients with active disease versus remission and in colonic versus ileal disease. GPER was significantly increased in active patients and correlated with BPA levels. BPA was significantly increased in patients with bacterial-DNA and correlated with serum endotoxin levels, (r = 0.417; P = .003). Serum butyrate and tryptophan levels were significantly lower in patients with bacterial-DNA and an inverse relationship was present between them and BPA levels (r = -0.491; P = .001) (r = -0.611; P = .001). Serum BPA levels correlated with IL-23 (r = 0.807; P = .001) and IL-17A (r = 0.743; P = .001). The multivariate analysis revealed an independent significant contribution of BPA and bacterial-DNA to serum levels of IL-23 and IL-17A. In conclusion, bisphenol A significantly affects systemic inflammatory response in CD patients with gut barrier disruption and dysbiotic microbiota secretory products in blood. These results provide evidence of an endocrine disruptor playing an actual pathogenic role on CD.


Subject(s)
Benzhydryl Compounds/blood , Crohn Disease/pathology , Dysbiosis/complications , Endocrine Disruptors/blood , Free Radical Scavengers/blood , Phenols/blood , Systemic Inflammatory Response Syndrome/pathology , Adult , Crohn Disease/blood , Crohn Disease/etiology , Cytokines/blood , DNA, Bacterial/blood , Female , Humans , Male , Prospective Studies , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/etiology
15.
J Sep Sci ; 44(16): 3052-3060, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34101988

ABSTRACT

Human exposure to bisphenols has rarely been reported. The most important challenges in this regard are the sensitivity and accuracy of the analytical methods employed. Dansyl chloride derivatization prior to high-performance liquid chromatography-tandem mass spectrometry has been prevalently employed to improve sensitivity. However, the dose effect of the derivatization reagent on the reaction products is not well understood, especially for reactants with two or more active groups. This study investigated the mass ratio of dansyl chloride to bisphenols and found the mass ratio played a vital role in changing the composition of derivatives; further, the optimal ratio for obtaining di-substituted derivatives was confirmed. Under optimal conditions, solid-phase extraction followed by dansyl chloride derivatization coupled with high-performance liquid chromatography-tandem mass spectrometry was used to detect eight bisphenols in human serum samples. The method detection limits of the eight bisphenols were 0.025-0.28 ng/mL, and the recoveries were 72.9-121.7% by spiking bisphenols (2, 5, and 20 ng/mL) into bovine serum. The detection frequencies of bisphenol A and bisphenol F in 73 serum samples obtained from children from Guangzhou were 41.1% and 71.2%, respectively, while the detection frequencies of other bisphenols were below 20%. The concentrations of bisphenol A and bisphenol F were < 0.28-8.0 ng/mL and < 0.028-7.6 ng/mL, respectively.


Subject(s)
Benzhydryl Compounds/blood , Chromatography, High Pressure Liquid/methods , Dansyl Compounds/analysis , Phenols/blood , Tandem Mass Spectrometry/methods , Animals , Calibration , Cattle , Child , China , Environmental Exposure , Equipment Design , Humans , Reproducibility of Results , Serum/metabolism , Solid Phase Extraction , Temperature
16.
Bioorg Med Chem Lett ; 44: 128121, 2021 07 15.
Article in English | MEDLINE | ID: mdl-34015506

ABSTRACT

Oxidative stress and inflammation have been considered the main factors in the liver injury of clofibrate (CF). To obtain a novel antihyperlipidemic agent with antioxidant, anti-inflammation and hepatoprotection, the combination of sesamol and clofibric acid moieties was performed and achieved sesamol-clofibrate (CF-Sesamol). CF-Sesamol showed significant hypolipidemia effects in hyperlipidemia mice induced by Triton WR 1339, reducing TG by 38.8% (P < 0.01) and TC by 35.1% (P < 0.01). CF-Sesamol also displayed an alleviating effect on hepatotoxicity. The hepatic weight and hepatic coefficient were decreased. The amelioration of liver function was observed, such as aspartate and lactate transaminases (AST and ALT), alkaline phosphatase (ALP) and total proteins (TP) levels. Liver histopathological examination showed that hepatocyte necrosis, cytoplasmic loosening, nuclear degeneration and inflammatory cell infiltration reduced obviously by treatment with CF-Sesamol. Related molecular mechanisms on hepatoprotection showed that CF-Sesamol up-regulated Nrf2 and HO-1 expression and down-regulated p-NF-κB p65 expression in hepatic tissues. CF-Sesamol has significant antioxidant and anti-inflammatory effects. Plasma antioxidant enzymes such as SOD and CAT increased, anti-lipid peroxidation product MDA decreased. The expression of TNF-α and IL-6 inflammatory cytokines in liver was significantly lower than that in the CF group. The results indicated that CF-Sesamol exerted more potent antihyperlipidemic effects and definite hepatoprotective activity partly through the Nrf2/NF-κB-mediated signaling pathway.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antioxidants/pharmacology , Benzodioxoles/pharmacology , Clofibric Acid/pharmacology , Hypolipidemic Agents/pharmacology , Phenols/pharmacology , Protective Agents/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Antioxidants/chemical synthesis , Antioxidants/chemistry , Benzodioxoles/blood , Benzodioxoles/chemistry , Clofibric Acid/blood , Clofibric Acid/chemistry , Dose-Response Relationship, Drug , Hyperlipidemias/chemically induced , Hyperlipidemias/drug therapy , Hypolipidemic Agents/chemical synthesis , Hypolipidemic Agents/chemistry , Inflammation/drug therapy , Inflammation/metabolism , Liver/drug effects , Liver/metabolism , Liver/pathology , Mice , Mice, Inbred Strains , Molecular Docking Simulation , Molecular Structure , Oxidative Stress/drug effects , Phenols/blood , Phenols/chemistry , Polyethylene Glycols , Protective Agents/chemical synthesis , Protective Agents/chemistry , Structure-Activity Relationship
17.
Reprod Biomed Online ; 43(1): 91-99, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34001442

ABSTRACT

RESEARCH QUESTION: Do bisphenol A (BPA) levels in maternal urine, serum and follicular fluid affect embryo quality and intracytoplasmic sperm hinjection (ICSI) cycle outcomes in women with unexplained infertility? DESIGN: Prospective study conducted between 1 April 2019 and 30 September 2019. The study cohort consisted of 82 women aged between 23 and 33 years who underwent intracytoplasmic sperm injection owing to unexplained infertility and provided urine, blood and follicular fluid samples on the day of oocyte retrieval. Consumption of drinking water from plastic carboys or bottles at home were considered as chronic BPA exposure. Demographic features and IVF outcomes of the patients were collected. RESULTS: Among the 82 women with unexplained infertility, clinical pregnancy was achieved in 22 (26.8%) patients after the IVF and embryo transfer cycle. The patients who consumed tap water had statistically significantly lower BPA values in three body fluids compared with patients who consumed plastic bottled water (all P < 0.001). Women who had grade 1 embryos transferred had lower serum BPA values than women who had grade 2 embryos transferred (10.8 ± 5.2 versus 26.9 ± 22 ng/ml, P = 0.003). Serum and follicular fluid BPA levels were statistically significantly higher in women who failed to achieve clinical pregnancy (P < 0.001, P = 0.006, respectively) and obtain a live birth (both P = 0.007). CONCLUSIONS: A negative relationship was found between serum and follicular fluid BPA levels and embryo quality, clinical pregnancy and live birth in these women. In addition, the BPA levels of women who consume tap water at home were lower than those who use plastic bottled water.


Subject(s)
Benzhydryl Compounds/adverse effects , Dietary Exposure/adverse effects , Estrogens, Non-Steroidal/adverse effects , Maternal Exposure/adverse effects , Phenols/adverse effects , Sperm Injections, Intracytoplasmic/statistics & numerical data , Adult , Benzhydryl Compounds/blood , Benzhydryl Compounds/urine , Drinking Water , Estrogens, Non-Steroidal/blood , Estrogens, Non-Steroidal/urine , Female , Follicular Fluid/chemistry , Humans , Phenols/blood , Phenols/urine , Pregnancy , Pregnancy Rate , Prospective Studies
18.
BMC Pharmacol Toxicol ; 22(1): 22, 2021 04 27.
Article in English | MEDLINE | ID: mdl-33906686

ABSTRACT

BACKGROUND: Low dose of NP exposure can alter adipose tissue formation, and the intake of high-fat diet (HFD) can also lead to the fatty liver disease. We investigated the combined effect of NP and HFD on the first offspring of rats, and whether this effect can be passed to the next generation and the possible mechanisms involved. METHODS: Pregnant rats had access to be treated with 5 µg/kg/day NP and normal diet. The first generation rats were given normal diet and HFD on postnatal day 21, respectively. Then the second generation rats started to only receive normal diet without NP or HFD. Body weight, organ coefficient of liver tissues, lipid profile, biochemical indexes and the expression of genes involved in lipid metabolism, as well as liver histopathology were investigated in male offspring of rats. RESULTS: NP and HFD interaction had significant effect on the birth weight, body weight and liver tissue organ coefficient of first generation male rats. And HFD aggravated abnormal lipid metabolism, even abnormal liver function and liver histopathological damage of first generation male rats produced by the NP. And this effect can be passed on to the second generation rats. HFD also accelerated the mRNA level of fatty acid synthesis genes such as Lpl, Fas, Srebp-1 and Ppar-γ of first generation rats induced by perinatal exposure to NP, even passed on to the second generation of male rats. NP and HFD resulted in synergistical decrease of the protein expression level of ERα in liver tissue in F2 male rats. CONCLUSION: HFD and NP synergistically accelerated synthesis of fatty acids in liver of male offspring rats through reducing the expression of ERα, which induced abnormal lipid metabolism, abnormal liver function and hepatic steatosis. Moreover, all of these damage passed on to the next generation rats.


Subject(s)
Diet, High-Fat , Endocrine Disruptors/toxicity , Fatty Acids/metabolism , Liver/drug effects , Phenols/toxicity , Prenatal Exposure Delayed Effects , Animals , Endocrine Disruptors/blood , Estrogen Receptor alpha/metabolism , Fatty Acid Synthase, Type I/genetics , Female , Gene Expression Regulation/drug effects , Lipoprotein Lipase/genetics , Liver/metabolism , Liver/pathology , Male , Maternal-Fetal Exchange , PPAR gamma/genetics , Phenols/blood , Pregnancy , Rats, Wistar , Sterol Regulatory Element Binding Protein 1/genetics
19.
J Sep Sci ; 44(9): 1893-1903, 2021 May.
Article in English | MEDLINE | ID: mdl-33650236

ABSTRACT

Sensitive analysis of very low-molecular weight metabolites using liquid chromatography with quadrupole-time-of-flight mass spectrometry is challenging due to the high losses of ions in a time-of-flight analyzer. Improvement in sensitivity for these analytes via the optimization of advanced parameters, including quadrupole profile, ion guide parameters, and duty cycle, has been achieved. The optimization of the method was carried out using a large spectrum of structurally different compounds including (iso)flavonoids and their known metabolites. These compounds can be categorized into two major groups, that is, compounds with (iso)flavonoid core and low-molecular weight phenolics. The optimization of the duty cycle enabled up to a 15-fold increase in analyte responses while the contribution of tuning ion optics and quadrupole profile was negligible. The limits of quantifications of our new method were assessed using both standard solutions and rat plasma. They were decreased at least 10 times for several low-molecular weight phenolics enabling measurement of their concentrations in a range of 1-50 ng/mL in rat plasma after protein precipitation. Concurrently, the limits of quantifications for compounds with (iso)flavonoid core did not increase distinctly allowing their detection in a range of 0.5-10 ng/mL. The new method was used for the targeting of phenolics in biological samples from pharmacokinetics experiments.


Subject(s)
Phenols/blood , Animals , Chromatography, High Pressure Liquid , Male , Mass Spectrometry , Rats , Rats, Wistar
20.
Reprod Toxicol ; 100: 83-89, 2021 03.
Article in English | MEDLINE | ID: mdl-33453334

ABSTRACT

Exposure to Bisphenol A (BPA) during early development particularly in- utero has been linked to a wide range of pathology. The aim of this study was to examine the relationship of BPA and its naturally occurring metabolite BPA-glucuronide (BPA-g) with sex steroid hormone levels in South African mother-child pairs. Third-trimester serum maternal samples and matching cord blood samples were analyzed for BPA, BPA-g and nine sex steroid hormones using liquid chromatography tandem mass spectrometry (LC-MS/MS). Sixty maternal and child pairs were analyzed. Rank correlation demonstrated a significant positive relationship between cord blood estradiol and cord blood BPA (p = 0.002) and maternal BPA levels (p = 0.02) respectively. Cord blood testosterone from male infants showed a negative Spearman's correlation (r=-0.5, p = 0.02) with maternal BPA-g. There was no statistical difference in total testosterone levels in cord blood from male and female infants. The findings of the current study indicate a significant relationship between some key sex steroid hormones namely testosterone, dihydrotestosterone and estradiol and fetal exposure BPA.


Subject(s)
Benzhydryl Compounds/blood , Fetal Blood/chemistry , Glucuronides/blood , Gonadal Steroid Hormones/blood , Phenols/blood , Adolescent , Adult , Dihydrotestosterone/blood , Endocrine Disruptors/blood , Estradiol/blood , Female , Humans , Infant, Newborn , Male , Pilot Projects , Pregnancy , Pregnancy Trimester, Third , South Africa , Testosterone/blood , Young Adult
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