Urinary Metabolite Concentrations Research Articles

Comparison of polycyclic aromatic hydrocarbon metabolite concentrations in urine of mothers and their newborns

Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants produced during incomplete combustion of organic matter. Humans can be exposed to them via several pathways (inhalation, digestion, dermal exposure). The aim of this study was to assess the concentration of 11 monohydroxylated metabolites of PAHs (OH-PAHs) in 660 urine samples collected from mothers and their newborns residing in two localities of the Czech Republic — Most and Ceske Budejovice — in 2016 and 2017. After enzymatic hydrolysis, the target analytes were extracted from the urine samples using liquid-liquid extraction, with extraction solvent ethyl acetate and a clean-up step using dispersive solid-phase extraction (d-SPE) with the Z-Sep sorbent. For identification and quantification, ultra-high performance liquid chromatography coupled with tandem mass spectrometry was applied. 2-OH-NAP was the compound present in all of the measured samples and it was also the compound at the highest concentration in both mothers' and newborns' urine samples (median concentration 5.15 μg/g creatinine and 3.58 μg/g creatinine). The total concentrations of OH-PAHs in urine samples collected from mothers were 2 times higher compared to their children. The most contaminated samples were collected in Most in the period October 2016–March 2017 from both mothers (12.59 μg/g creatinine) and their newborns (8.29 μg/g creatinine). The concentrations of OH-PAHs in urine samples, which were collected from both mothers and their newborns as presented in this study, are comparable with those found in our previous study between 2013 and 2014. In addition, they are slightly lower or comparable to other studies from Poland, USA, Germany, China, and Australia. The results might indicate that the population in the previously highly air-polluted mining districts carries some long-term changes (maybe existing changes in genetic information), which also affect the metabolism of PAHs. It could be related to the long-lasting effect, and thus corresponding to the shortened life expectancy.

Association of urinary concentrations of phthalate metabolites with quinolinic acid among women: A potential link to neurological disorders

BackgroundQuinolinic acid (QA), a neuroactive metabolite produced during tryptophan degradation, is implicated in the pathogenesis of several neurological disorders. Phthalates are structurally similar to QA, and exposure to phthalates has demonstrated increased QA production and excretion in rodent studies. We recently showed that very high exposure to dibutyl phthalate was associated with higher concentrations of urinary QA in men. However, no human studies examined the associations between background (low) phthalate exposures and QA. ObjectivesTo examine the associations of urinary concentrations of phthalate metabolites with QA. MethodsFemale participants (N = 126) who participated in a prospective cohort study at the Massachusetts General Hospital Fertility Center provided 758 urine samples (273 during pregnancy and 485 during non-pregnancy). Concentrations of 11 phthalate metabolites and QA in urine were measured. We used multivariable linear mixed effect models to estimate the percent change in urinary QA concentrations associated with a doubling (100%) of urinary phthalate metabolite concentration, and evaluated whether there was effect modification by pregnancy status. ResultsWomen’s mean (standard deviation) age was 34.2 (4.0) years with a body mass index of 23.5 (3.7) kg/m2. The women were primarily Caucasian (92%), had at least a college degree (98%), and none were current smokers. Pairwise Spearman correlations between concentrations for phthalate metabolites and QA measured in the same urine samples ranged from 0.36 for MEHP to 0.68 for dibutyl phthalate (DBP) metabolites. In multivariable-adjusted models, the percent change in urinary QA concentrations was significantly higher for each doubling of several urinary phthalate metabolite concentrations. For example, each doubling of DBP metabolites was associated with a 13.7% (95%CI: 10.6, 16.9)% higher QA. Associations between the low molecular weight phthalate metabolites and QA were stronger among samples collected during pregnancy as compared to non-pregnancy samples from the same women. ConclusionsUrinary concentrations of several phthalate metabolites were positively associated with QA among women. These findings, along with the known neurotoxicity of QA, warrant the need to examine whether QA concentrations may serve as a pathway for the adverse neurodevelopment outcomes found in children’s health studies.

Erratum: "Prenatal Exposure to DDT and Pyrethroids for Malaria Control and Child Neurodevelopment: The VHEMBE Cohort, South Africa".

Erratum: "Prenatal Exposure to DDT and Pyrethroids for Malaria Control and Child Neurodevelopment: The VHEMBE Cohort, South Africa".

Association between polycyclic aromatic hydrocarbons exposure and bone turnover in adults.

Cigarette smoking is a risk factor of osteoporosis and bone fracture. Tobacco smoke contains several polycyclic aromatic hydrocarbons. Thus, we hypothesized that environmental polycyclic aromatic hydrocarbon exposure is associated with bone loss and fracture risk. The present study examined the association between polycyclic aromatic hydrocarbon exposure and bone turnover in the general adult population. A total of 1408 eligible participants from the National Health and Nutrition Examination Survey (NHANES 2001-2006) were included in this cross-sectional analysis. The levels of urinary N-telopeptide and serum bone-specific alkaline phosphatase, which are biomarkers of bone resorption and formation, respectively, were assessed. Meanwhile, polycyclic aromatic hydrocarbon exposure was evaluated using the concentrations of urinary polycyclic aromatic hydrocarbon metabolites. The association between polycyclic aromatic hydrocarbon exposures and N-telopeptide, and bone-specific alkaline phosphatase levels was assessed using a multivariate linear regression model. All polycyclic aromatic hydrocarbon metabolites except 3-phenanthrene were significantly associated with increased N-telopeptide levels (P < 0.05) after adjustment of relevant covariables. However, no significant relationship was observed between polycyclic aromatic hydrocarbon metabolites and bone-specific alkaline phosphatase levels. This relationship remained significant after the participants were assessed according to sex (P < 0.05). Additionally, all polycyclic aromatic hydrocarbon metabolites showed a positive association with N-telopeptide levels in participants aged <60 years (P < 0.05). Polycyclic aromatic hydrocarbon exposure is associated with increased bone resorption among the general adult population in the United States. Further studies must assess the potential mechanisms associated with the adverse effects of polycyclic aromatic hydrocarbon exposure on bone loss.

Predictors of phthalate metabolites in urine and follicular fluid and correlations between urine and follicular fluid phthalate metabolite concentrations among women undergoing in vitro fertilization

BackgroundPhthalate metabolites in follicular fluid (FF) may negatively affect normal folliculogenesis; however, the predictors of phthalate metabolite concentrations in urine and FF and relationships between urine and FF phthalate metabolite concentrations among women undergoing in vitro fertilization (IVF) are poorly understood. ObjectiveTo investigate predictors of phthalate metabolites in urine and FF and correlations between urine and FF phthalate metabolite concentrations among women undergoing IVF. MethodWe recruited 305 women seeking infertility treatment at a reproductive center in Wuhan, China, from October to November 2016. Information regarding demographic characteristics, personal care product use and plastic material contact was obtained through direct interviews. Concentrations of 8 phthalate metabolites in urine and FF samples were measured using high-performance liquid chromatography and tandem mass spectrometry. Associations regarding metabolite concentrations in urine and FF samples were analysed by Spearman's correlation and linear regression. Generalized linear regression was used to examine potential predictors of phthalate metabolite concentrations in urine and FF. ResultsWeak to moderate associations between urine and FF samples were found for monoethyl phthalate (MEP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) (correlation coefficient: MEP, 0.350; MEOHP, 0.377); no associations were observed for other metabolites. The predictive powers of urinary metabolite concentrations in determining FF metabolite concentrations were uniformly low, with R2 ≤ 0.113. Body mass index (BMI) and educational level were inversely associated with the urinary concentrations of certain metabolites. Higher household income, intake of bottled drinks within 48 h, and use of shower gel and soap were frequently associated with higher urinary metabolite concentrations. BMI, higher household income and use of disposable plastic cups within 48 h were associated with higher metabolite concentrations in FF. ConclusionPhthalate metabolite concentrations in urine and FF vary according to sociodemographic characteristics and lifestyle factors. Phthalate metabolite concentrations in urine may not be appropriate for estimating ovary phthalate exposure.

Polycyclic aromatic hydrocarbons (PAH) in urine of children and adolescents in Germany - human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V).

Polycyclic aromatic hydrocarbons (PAH) mainly originate from incomplete combustion of organic materials and are, among other sources, found in traffic emissions, smoked or barbecued food, leafy vegetables, and tobacco smoke. Some PAH or their metabolites are hazardous for health and classified as carcinogenic, mutagenic, or toxic to reproduction. Urine samples from 3- to 17-year-old children and adolescents living in Germany were analysed for concentrations of metabolites of the PAH fluorene, naphthalene, phenanthrene, and pyrene in the population-representative German Environmental Survey for Children and Adolescents GerES V (2014-2017). PAH metabolites were analysed in urine samples of 516 participants and could be quantified in 88-100% of the samples. Geometric mean concentrations were: 0.785μg/L (0.688 μg/gcreatinine) for 1-OH-naphthalene, 4.233μg/L (3.706 μg/gcrea) for 2-OH-naphthalene, 0.139μg/L (0.122 μg/gcrea) for 1-OH-phenanthrene, 0.085μg/L (0.075 μg/gcrea) for 2-OH-phenanthrene, 0.131μg/L (0.115 μg/gcrea) for 3-OH-phenanthrene, 0.045μg/L (0.040 μg/gcrea) for 4-OH-phenanthrene, 0.058μg/L (0.050 μg/gcrea) for 9-OH-phenanthrene, 0.511μg/L (0.448 μg/gcrea) for Σ-OH-phenanthrene, and 0.099μg/L (0.087 μg/gcrea) for 1-OH-pyrene. Analyses of subgroups revealed higher PAH metabolite concentrations in young children compared to adolescents, and also in residents of former East Germany compared to those living in former West Germany. Increased urinary PAH metabolite concentrations were found in participants using domestic fuel for heating or gas for cooking. Plastic objects were identified as another potential source of exposure. Urinary concentrations of naphthalene and fluorene metabolites were elevated in active smokers and to the same extent in non-smokers exposed to passive smoking. Comparison with previous cycles of GerES revealed a decrease over time and a further decline in the still significant differences in urinary PAH metabolite concentrations of participants living in former East versus West Germany.

Gut microbiota generation of protein-bound uremic toxins and related metabolites is not altered at different stages of chronic kidney disease

Chronic kidney disease (CKD) is characterized by accumulation of protein-bound uremic toxins such as p-cresyl sulfate, p-cresyl glucuronide, indoxyl sulfate and indole-3-acetic acid, which originate in the gut. Intestinal bacteria metabolize aromatic amino acids into p-cresol and indole, (further conjugated in the colon mucosa and liver) and indole-3-acetic acid. Here we measured fecal, plasma and urine metabolite concentrations; the contribution of gut bacterial generation to plasma protein-bound uremic toxins accumulation; and influx into the gut of circulating protein-bound uremic toxins at different stages of CKD. Feces, blood and urine were collected from 14 control individuals and 141 patients with CKD. Solutes were quantified by ultra-high performance liquid chromatography. To assess the rate of bacterial generation of p-cresol, indole and indole-3-acetic acid, fecal samples were cultured exvivo. With CKD progression, an increase in protein-bound uremic toxins levels was observed in plasma, whereas the levels of these toxins and their precursors remained the same in feces and urine. Anaerobic culture of fecal samples showed no difference in exvivo p-cresol, indole and indole-3-acetic acid generation. Therefore, differences in plasma protein-bound uremic toxins levels between different CKD stages cannot be explained by differences in bacterial generation rates in the gut, suggesting retention due to impaired kidney function as the main contributor to their increased plasma levels. Thus, as fractional clearance decreased with the progression of CKD, tubular clearance appeared to be more affected than the glomerular filtration rate, and there was no net increase in protein-bound uremic toxins influx into the gut lumen with increased plasma levels.

The influence of demographic and lifestyle factors on urinary levels of PAH metabolites-empirical analyses of Cycle 2 (2009-2011) CHMS data.

Polycyclic aromatic hydrocarbons (PAHs) are a group of compounds formed during the incomplete combustion of organic matter. Several are mutagenic carcinogens; the magnitude of exposure can be assessed by examining urinary levels of PAH metabolites. Data from biomonitoring studies that record urinary PAH metabolite levels, as well as demographic and lifestyle information, can be used to investigate relationships between PAH exposure and variables, such as smoking status, workplace smoking restrictions, age, sex, household income, home age, and occupation. This study analysed creatinine-adjusted urinary PAH metabolite concentrations and questionnaire data from ~1200 individuals aged 16 years and older surveyed in Cycle 2 of the Canadian Health Measures Survey (CHMS). Statistical analyses revealed that smoking status, age, and sex are associated with urinary concentrations of a pyrene metabolite (1-OHP), phenanthrene metabolites (ΣOH-Phen), fluorene metabolites (ΣOH-Flu) and naphthalene metabolites (ΣOH-Nap). More specifically, smoking status, age and sex can collectively account for 30, 24, 52, and 34% of the observed variations in 1-OHP, ΣOH-Phen, ΣOH-Flu and ΣOH-Nap metabolites, respectively (p < 0.001). Analyses of non-smokers revealed weak but significant effects of age, sex, home age, and occupation on urinary levels of selected PAH metabolites (i.e., <7% of observed variation, p < 0.05). The unexplained variation in PAH metabolite levels is most likely related to diet, which was not examined. Although the results revealed significant relationships between urinary PAH metabolite levels and several lifestyle and/or demographic variables, robust examinations of selected effects (e.g., sex, home age, occupation) will require datasets that are balanced with respect to the other highlighted variables. The results can be used to identify remedial measures to reduce exposure and concomitant risk, and/or design follow-up studies to test hypotheses regarding the causes of exposure differences empirically related to sex, age, home age, and occupation.

Organophosphate esters in a cohort of pregnant women: Variability and predictors of exposure

Organophosphate esters (OPEs) are a group of chemicals used as flame retardants and plasticizers that replaced polybrominated diphenyl ethers in consumer products such as furniture and electronics. To characterize exposure to OPEs during fetal development, we measured urinary OPE metabolite concentrations in women twice during pregnancy (16 and 26 weeks' gestation) and at delivery (n = 357). We also previously quantified house dust OPE parent compound concentrations at 20 weeks’ gestation (n = 317). Diphenyl phosphate (DPHP) had the highest geometric mean urinary concentrations (1.5–2.3 μg/g creatinine), followed by bis(1,3-dichloro-2-propyl) phosphate (BDCIPP; 0.75–0.99 μg/g creatinine), and bis(2-chloroethyl) phosphate (BCEP; 0.72–0.97 μg/g creatinine), while dibutyl phosphate (DNBP) had the lowest concentrations (0.25–0.28 μg/g creatinine). Urinary OPE metabolites were moderately correlated with each other at 26 weeks (rs: 0.23–0.38, p < 0.001) while the correlations at 16 weeks and delivery were slightly weaker. Intra-class correlations for urinary metabolites measured at three time points were poor (0.16–0.34), indicating high variability within individuals. Dust concentrations of OPE parent compounds were associated with BCEP, BDCIPP, and DPHP concentrations in urine at some but not all time points. In linear mixed models of urinary OPE metabolite concentrations, household size was inversely associated with BCEP concentrations, and being non-white was associated with lower BDCIPP and DPHP concentrations. Urine samples collected in the summer had the highest OPE metabolite concentrations. This study highlights the need to collect multiple urine samples during pregnancy to define exposure patterns and investigate potential periods of susceptibility.

Association between higher urinary normetanephrine and insulin resistance in a Japanesepopulation.

Since activation of the sympathetic nervous system is associated with both impaired insulin secretion and insulin resistance, or namely with diabetes, evaluation of such activation in ordinary clinical settings may be important. Therefore, we evaluated the relationships between urinary concentrations of the catecholamine metabolites, urinary normetanephrine (U-NM) and urinary metanephrine (U-M), and glucose metabolism in a general population. From 1,148 participants in the 2016 population-based Iwaki study of Japanese, enrolled were 733 individuals (gender (M/F): 320/413; age: 52.1±15.1), who were not on medication affecting serum catecholamines, not diabetic, and had complete data-set and blood glucose levels appropriate for the evaluation of insulin secretion and resistance, using homeostasis model assessment (HOMA-β and HOMA-R, respectively). Univariate linear regression analyses revealed significant correlations between both U-NM and U-M, and HOMA-β, but adjustment for multiple factors correlated with HOMA indices abolished these (β = -0.031, p = 0.499, and β = -0.055, p = 0.135, respectively). However, the correlation between U-NM and HOMA-R observed using univariate linear regression analysis (β = 0.132, p<0.001) remained significant even after these adjustments (β = 0.107, p = 0.007), whereas U-M did not correlate with HOMA-R. Furthermore, use of the optimal cut-off value of U-NM for the prediction of insulin resistance (HOMA-R >1.6) determined by ROC analysis (0.2577 mg/gCr) showed that individuals at risk had an odds ratio of 2.65 (confidence interval: 1.42-4.97) after adjustment for the same factors used above. Higher U-NM concentrations within the physiologic range are a significant risk factor for increased insulin resistance in a general Japanese population.

Urinary metabolites of organophosphate esters in women and their relationship with serum lipids: An exploratory analysis

Organophosphate esters (OPEs) are high-production volume chemicals. Use of OPEs has largely increased since the phase-out/ban of polybrominated diphenyl ethers (PBDEs). The ubiquitous occurrence of OPEs, in higher concentrations in abiotic matrices than brominated flame retardants (BFRs), is a concern because several of the OPEs have been linked to adverse health effects. In this study, urinary metabolites of OPEs were measured in a subset of a population-based sample of women of child bearing age recruited in Ontario, and associations between serum lipid levels and urinary concentrations of OPE metabolites were evaluated. Urine samples (n = 120) were extracted using automated solid phase extraction and analysed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Diphenyl phosphate (DPHP), bis(2-chloropropyl) phosphate (BCIPP) and bis(1,3-dichloro-2 propyl) phosphate (BDCIPP) were detected with frequencies of 100%, 76% and 75% at median concentrations of 13.8 ng/mL, 0.5 ng/mL and 1.8 ng/mL, respectively. Bis(2-chloroethyl) hydrogen phosphate (BCEP) and di-cresyl phosphate (DCP; mixture of 3 isomers) were detected in 52% and 42% of the samples, respectively. Detected at lower frequencies were 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP, 29%), bis-2(butoxyethyl) phosphate (BBOEP, 11%), and desbutyl-tris-(2-butoxy-ethyl) phosphate (desbutyl TBOEP, 9%). Using multiple regression model, a negative statistically significant correlation was observed between BCEP and cholesterol (p = 0.04), as well as BCEP and total lipid (p = 0.04). Whereas BCIPP was positively and significantly correlated with cholesterol (p = 0.003) and LDL (p = 0.001). Additional work to further explore these relationships and to evaluate more recently identified OPE metabolites is warranted.

Phthalate Exposure, Metabolism Capability, and Breast Cancer Risk: Case-Control Analysis Nested in a Large-Scale Long-Term Follow-Up Cohort

Background : Phthalates are widely used in a variety of products from plastics to personal-care items. Their estrogenic activity may increase breast cancer risk, but the causality in humans was rarely assessed by longitudinal cohort studies. Method: This case-control study nested in a large-scale long-term follow-up cohort. A total of 119 newly developed cases of breast cancer and 245 matched controls were selected from a community-based cohort of 11,923 female participants, who were enrolled in 1991-1992 and followed to 2010 in Taiwan. Eleven metabolites of seven phthalates in urine samples collected at entry and follow-up examinations were measured using liquid chromatography/electrospray ionization tandem mass spectrometry. The DEHP metabolism capability was evaluated by the percentages of specific metabolite in total DEHP metabolites. Finding : Elevated urinary concentrations of total DEHP metabolites (>0·38 μmol/g creatinine) combined with elevated percentages of MEHP in total DEHP metabolites level (MEHP% >6·7%) had an increased odds ratio (OR) of breast cancer (OR= 2·68, 95% confidence interval, 1·47-4·89) after adjustment for age at menarche. There were no significant associations between the breast cancer risk and the baseline urinary concentrations of MEP, MMP, MiBP, MnBP, and MBzP, while MiNP was not detected in all urine samples. Analysis of 115 pairs of urine samples collected at study entry and follow-up visit showed higher correlation coefficients for the percentage of specific DEHP metabolite in total DEHP metabolites than for the urinary concentration of specific DEHP metabolites. Interpretation: The findings suggest that high DEHP exposure and high MEHP percentage may increase the risk of breast cancer, and DEHP metabolism capability is more stable than DEHP exposure over time. Funding Statement: Supported by grants (EH-102-SP-01 and EH-103-SP-01) from National Health Research Institutes, Ministry of Health and Welfare, as well as grant (MOST 103-2314-B-001-005-MY3) from the Ministry of Science and Technology, Executive Yuan, Taipei, Taiwan. Declaration of Interests: We declare that we have no conflict of interest and none of the funding organization played a role in the design and conducted of this study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript. Ethics Approval Statement: This study was approved by the Institutional Review Board of the National Taiwan University College of Public Health and by the National Health Research Institutes (NHRI).

Ten-year temporal trends (2006-2015) and seasonal-differences in urinary metabolite concentrations of novel, hygiene-used pyrethroids in Japanese children.

Metofluthrin, profluthrin, tefluthrin, and transfluthrin are pyrethroid (PYR) insecticides increasingly used to control mosquitoes, flies, and moths in households and public places (hygiene-PYRs). Currently, there is limited data available concerning exposure to these novel hygiene-PYRs. The goal of this study was to monitor exposure to these hygiene-PYRs by analysing their urinary metabolites and to investigate the temporal and seasonal trends in the concentrations of these metabolites. First morning urine samples were obtained from 50 Japanese children (four-six years old) in October of 2006, 2011, and 2015 (total=150 children) in order to investigate temporal trends. Additionally, first-morning urine samples were collected from 44 three-year-old children in August-September of 2012 (summer) and in February of 2013 (winter) to investigate seasonal differences. The urinary concentrations of 2,3,5,6-tetrafluorobenzyl alcohol (FB-Al; a specific metabolite of transfluthrin), 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (CH3-FB-Al; a common metabolite of tefluthrin and profluthrin), 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (CH3OCH2-FB-Al; a specific metabolite of metofluthrin), and 2,3,5,6-tetrafluoro-1,4-benzenedimethanol (HOCH2-FB-Al; a common metabolite of metofluthrin, tefluthrin, and profluthrin) were measured using GC-MS/MS. For the investigated years, rapid increases in the detection rates of the hygiene-PYR metabolites were observed. In 2015, FB-Al was identified in 64% of the samples, CH3-FB-Al in 46%, CH3OCH2-FB-Al in 50%, and HOCH2-FB-Al in 83%. Significant increasing trends were found for the concentrations of all hygiene-PYR metabolites from 2006 to 2015 (Jonckheere-Terpstra test, p<0.001). The concentrations of FB-Al and CH3OCH2-FB-Al were higher in summer than in winter (Mann Whitney-U test, p<0.05). These findings suggest that, in Japanese children, exposure to hygiene-PYRs has increased over the past decade, and that children are exposed to higher levels of hygiene-PYRs in summer than in winter.

Distortion product otoacoustic emission sensitivity to different solvents in a population of industrial painters

Objective: To evaluate the ototoxic effect of the exposure to different organic solvents and noise using distortion product otoacoustic emissions (DPOAEs).Design: The exposure to different solvents was evaluated by measuring, before and at the end of the work-shift, the urinary concentrations of solvent metabolites used as dose biomarkers. The urinary concentrations of DNA and RNA oxidation products were also measured as biomarkers of oxidative damage. The simultaneous exposure to noise was also evaluated. DPOAEs and pure tone audiometry (PTA) were used as outcome variables, and were correlated to the exposure variables using mixed effect linear regression models.Study sample: Seventeen industrial painters exposed to a solvent mixture in a naval industry. A sample size of 15 was estimated from previous studies as sufficient for discriminating small hearing level and DPOAE level differences (5 dB and 2 dB, respectively) at a 95% confidence level.Results: Statistically significant associations were found between the DPOAE level and the urinary dose biomarkers and the oxidative damage biomarkers. DPOAE level and the logarithm of the metabolite concentration showed a significant negative correlation.Conclusions: DPOAE are sensitive biomarkers of exposure to ototoxic substances and can be effectively used for the early detection of hearing dysfunction.

3,5-T2-A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action.

Over the last decades, thyroid hormone metabolites (THMs) received marked attention as it has been demonstrated that they are bioactive compounds. Their concentrations were determined by immunoassay or mass-spectrometry methods. Among those metabolites, 3,5-diiodothyronine (3,5-T2), occurs at low nanomolar concentrations in human serum, but might reach tissue concentrations similar to those of T4 and T3, at least based on data from rodent models. However, the immunoassay-based measurements in human sera revealed remarkable variations depending on antibodies used in the assays and thus need to be interpreted with caution. In clinical experimental approaches in euthyroid volunteers and hypothyroid patients using the immunoassay as the analytical tool no evidence of formation of 3,5-T2 from its putative precursors T4 or T3 was found, nor was any support found for the assumption that 3,5-T2 might represent a direct precursor for serum 3-T1-AM generated by combined deiodination and decarboxylation from 3,5-T2, as previously documented for mouse intestinal mucosa. We hypothesized that lowered endogenous production of 3,5-T2 in patients requiring T4 replacement therapy after thyroidectomy or for treatment of autoimmune thyroid disease, compared to production of 3,5-T2 in individuals with intact thyroid glands might contribute to the discontent seen in a subset of patients with this therapeutic regimen. So far, our observations do not support this assumption. However, the unexpected association between high serum 3,5-T2 and elevated urinary concentrations of metabolites related to coffee consumption requires further studies for an explanation. Elevated 3,5-T2 serum concentrations were found in several situations including impaired renal function, chronic dialysis, sepsis, non-survival in the ICU as well as post-operative atrial fibrillation (POAF) in studies using a monoclonal antibody-based chemoluminescence immunoassay. Pilot analysis of human sera using LC-linear-ion-trap-mass-spectrometry yielded 3,5-T2 concentrations below the limit of quantification in the majority of cases, thus the divergent results of both methods need to be reconciliated by further studies. Although positive anti-steatotic effects have been observed in rodent models, use of 3,5-T2 as a muscle anabolic, slimming or fitness drug, easily obtained without medical prescription, must be advised against, considering its potency in suppressing the HPT axis and causing adverse cardiac side effects. 3,5-T2 escapes regular detection by commercially available clinical routine assays used for thyroid function tests, which may be seriously disrupted in individuals self-administering 3,5-T2 obtained over-the counter or from other sources.

Systemic effects of platelet-rich plasma local injection on serum and urinary anabolic metabolites: A prospective randomized study.

Platelet-rich plasma (PRP) is widely utilized in the treatment of sports injuries. However, potential systemic effects after localized PRP injection are unclear at present. In this prospective randomized study, 24 Taiwanese male athletes with tendinopathy were randomized into a PRP group (n = 13) or a saline group (n = 11). The concentrations of serum and urine biomarkers were quantified by enzyme-linked immunosorbent assay assessment as well as gas chromatographic and mass spectrometric analysis, respectively. The results showed no significant differences in serum levels of growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein 3, vascular endothelial growth factor, platelet-derived growth factor-BB, or serum substance P(SP) between the two groups before intervention, nor at 1, 2, or 7 days after intervention. However, a significant decrease in the serum SP level 1 and 7 days after PRP injection was observed. Regarding urinary concentrations of metabolites of anabolic androgenic steroids (AAS), no between-group differences before intervention, nor at 1, 2, or 7 days after intervention, were observed. Our study failed to observe significant surge of serum anabolic molecules and urinary excretion of anabolic AAS metabolites after PRP injection.

Urinary organophosphate ester concentrations in relation to ultra-processed food consumption in the general US population

BackgroundUltra-processed foods are highly processed foods which are manufactured with industrial substances to increase convenience and palatability. Some organophosphate esters (OPEs) are used as flame retardants and plasticizers and have been detected in food samples, particularly processed foods. However, little is known about dietary sources of OPEs or whether higher consumption of ultra-processed foods increases exposures. ObjectivesWe evaluated whether higher consumption of ultra-processed food is associated with urinary OPE metabolite concentrations in a nationally representative sample of US children and adults. MethodsAmong 2242 participants (≥6 years) in the National Health and Nutrition Examination Survey (NHANES) 2013–2014, we used the NOVA classification system to calculate percent of total energy from ultra-processed food using a 24 h dietary recall. Concentrations of 7 OPE metabolites, including diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), dibutyl phosphate (DBUP), di-p-cresyl phosphate (DPCP), 2,3,4,5-tetrabromobenzoic acid (TBBA), and bis(1-chloro-2-propyl) phosphate (BCPP) were measured in urine. We used multivariable linear or logistic regressions to examine associations per 10% higher total energy from ultra-processed foods with percent changes or prevalence of detectable levels of creatinine-standardized OPEs. ResultsIn a model adjusting for only urinary creatinine, each 10% higher total energy from ultra-processed food was associated with 3.5% (95% CI: 0.7%, 6.3%) higher DPHP and 8.2% (95% CI: 4.6, 11.9%) higher BDCPP concentrations. However, none of the OPE metabolites was associated with ultra-processed food consumption in models adjusted for sociodemographic characteristics, health behaviors, and BMI (all p-values >0.05). Ultra-processed breads and tortillas; sauces, dressing, and gravies; and milk-based drinks were associated with higher concentrations of BDCPP while frozen and shelf-stable plate meals were associated with lower concentrations. Reconstituted meat or fish products and ultra-processed milk-based desserts were associated with greater odds of detectable levels of BCPP. ConclusionWhile some food groups were associated with urinary OPE metabolite concentrations, ultra-processed foods do not appear to be a major source of current OPE exposure in the US.

Monitoring of urinary phthalate metabolites among pregnant women in Isfahan, Iran: the PERSIAN birth cohort.

Recently, increasing evidences have shown that the exposure to phthalates can adversely affect health status of pregnant women and their newborns. However, only a limited number of studies have investigated the concentrations of these compounds in the body fluids of pregnant women. In the present study, we aimed to evaluate the concentrations of phthalate metabolites in urinary samples of pregnant women in correlation with the population characteristics and different lifestyle factors. The study was conducted in 2018-2019 and urinary samples were taken from 121 pregnant women during their first pregnancy trimester who lived in Isfahan, Iran. The concentrations of monobutyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), and mono (2-ethyl-5hydroxyhexyl) phthalate (MEHHP) metabolites in urinary samples were determined by gas chromatography mass spectrometry (GC/MS). The socio-demographic profile of the participants (maternal education, age, family income, pre-pregnancy BMI), their lifestyle information (smoking habit, food pattern, and physical activity), cleaning products use data (cosmetic and household cleaning products) were collected by the use of PERSIAN birth cohort questionnaire. MBzP, MBP, MEHP, and MEHHP were detected in 100% of participated pregnant women with the mean concentration of 342.5 ± 193.8, 308.5 ± 229.4, 126.5 ± 118.3, and 866.5 ± 307.6μg/g creatinine, respectively. Significant correlations were observed between the mean concentration of urinary phthalate metabolites with the following variables: using plastic packaging (for bread, lemon juice, pickle, leftover, and water), lower physical activity, passive smoking exposure during pregnancy (p value<0.05). Furthermore, the pre-pregnancy BMI (r = 0.27, r = 0.3, r = 0.26, and r = 0.26), use of the household cleaning products (r = 0.2, r = 0.22, r = 0.3, and r = 0.26), utilize of the cosmetic products (r = 0.46, r = 0.48, r = 0.49, and r = 0.54), and passive smoking status (r = 0.5, r = 0.44, r = 0.44, and r = 0.26) directly correlated with the urinary concentrations of MBP, MBzP, MEHP, and MEHHP, respectively. No significant association was seen between the concentration of urinary phthalate metabolites with the maternal education level and family income. According to our findings, higher amounts of phthalate metabolites were detected in urinary samples of pregnant women who were passive smokers, or had higher pre-pregnancy BMI and lower physical activity, as well as those women who used higher amounts of cosmetic and household cleaning products, or used plastic packaging for food and non-food products.

Investigation of diagnostic performance of five urinary cholesterol metabolites for Niemann-Pick disease type C

Niemann-Pick disease type C (NPC) is an autosomal recessive disorder characterized by progressive nervous degeneration. Because of the diversity of clinical symptoms and onset age, the diagnosis of this disease is difficult. Therefore, biomarker tests have attracted significant attention for earlier diagnostics. In this study, we developed a simultaneous analysis method for five urinary conjugated cholesterol metabolites, which are potential diagnostic biomarkers for a rapid, convenient, and noninvasive chemical diagnosis, using LC/MS/MS. By the method, their urinary concentrations were quantified and the NPC diagnostic performances were evaluated. The developed LC/MS/MS method showed high accuracy and satisfied all analytical method validation criteria. When the urine of healthy controls and patients with NPC was analyzed, three of five urinary conjugated cholesterol metabolite concentrations corrected by urinary creatinine were significantly higher in the patients with NPC. As a result of receiver operating characteristics analysis, these urinary metabolites might have excellent diagnostic marker performance. 3β-Sulfooxy-7β-hydroxy-5-cholenoic acid showed particularly excellent diagnostic performance with both 100% clinical sensitivity and specificity, suggesting that it is a useful NPC diagnostic marker. The urinary conjugated cholesterol metabolites exhibited high NPC diagnostic marker performance and could be used for NPC diagnosis.

Associations of urinary di-(2-ethylhexyl) phthalate metabolites with the residential characteristics of pregnant women

Epidemiological evidence on the associations between urinary di-(2-ethylhexyl) phthalate (DEHP) metabolites and residential characteristics is limited. Therefore, we investigated the associations of urinary DEHP metabolites with the residential characteristics of pregnant women. We collected completed questionnaires and maternal spot urine samples from 616 random pregnant women in Shengjing Hospital of China Medical University in Shenyang. Urinary DEHP metabolites concentrations, including mono-(2-ethylhexyl) phthalate (MEHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), were measured and analyzed by Gas Chromatography-Mass Spectrometry (GC–MS). Multivariable linear regression models were performed to obtain regression estimates (β) and 95% confidence intervals (CIs) after adjustment for sociodemographic characteristics. In all participants, the geometric mean of MEHP and MEHHP concentrations were 4.25 ± 4.34 and 5.72 ± 2.65 μg/L, respectively. In multivariable analyses after adjusting for sociodemographic characteristics, distance from residence to motor vehicle traffic (≥150 m versus <20 m) was negatively associated with MEHP (β = −0.241, 95% CI: −0.448, −0.033) and MEHHP (β = −0.279, 95% CI: −0.418, −0.140) concentrations. Compared with the one that had not recently been renovated, a renovated home was associated with higher MEHP (β = 0.194, 95% CI: 0.064, 0.324) and MEHHP (β = 0.111, 95% CI: 0.024, 0.197) concentrations. Air freshener use was associated with higher MEHP (β = 0.322, 95% CI: 0.007, 0.636) concentrations. Moldy walls were positively associated with MEHP (β = 0.299, 95% CI: 0.115, 0.482) and MEHHP (β = 0.172, 95% CI: 0.050, 0.294) concentrations. In contrast, humidifier use was associated with a lower MEHP concentration (β = −0.167, 95% CI: −0.302, −0.032). Residential characteristics were probably associated with the DEHP exposure of pregnant women in Shenyang. Living near the motor vehicle traffic, residential renovation, air freshener use, and moldy walls are likely risk factors for increased DEHP exposure, whereas using household humidifier could be considered a protective measure to reduce DEHP exposure.