Triclosan administration to humanized UDP-glucuronosyltransferase 1 neonatal mice induces UGT1A1 through a dependence on PPARα and ATF4.

Triclosan (TCS) is an antimicrobial toxicant found in a myriad of consumer products and has been detected in human tissues, including breastmilk. We have evaluated the impact of lactational TCS on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) neonatal mice. In hUGT1 mice, expression of the hepatic UGT1A1 gene is developmentally delayed resulting in elevated total serum bilirubin (TSB) levels. We found that newborn hUGT1 mice breastfed or orally treated with TCS presented lower TSB levels along with induction of hepatic UGT1A1. Lactational and oral treatment by gavage with TCS leads to the activation of hepatic nuclear receptors constitutive androstane receptor (CAR), peroxisome proliferator-activated receptor alpha (PPARα), and stress sensor, activating transcription factor 4 (ATF4). When CAR-deficient hUGT1 mice (hUGT1/Car-/-) were treated with TCS, TSB levels were reduced with a robust induction of hepatic UGT1A1, leaving us to conclude that CAR is not tied to UGT1A1 induction. Alternatively, when PPARα-deficient hUGT1 mice (hUGT1/Pparα-/-) were treated with TCS, hepatic UGT1A1 was not induced. Additionally, we had previously demonstrated that TCS is a potent inducer of ATF4, a transcriptional factor linked to the integrated stress response. When ATF4 was deleted in liver of hUGT1 mice (hUGT1/Atf4ΔHep) and these mice treated with TCS, we observed superinduction of hepatic UGT1A1. Oxidative stress genes in livers of hUGT1/Atf4ΔHep treated with TCS were increased, suggesting that ATF4 protects liver from excessive oxidative stress. The increase oxidative stress may be associated with superinduction of UGT1A1. The expression of ATF4 in neonatal hUGT1 hepatic tissue may play a role in the developmental repression of UGT1A1.

Wastewater contaminants in a fractured bedrock aquifer and their potential use as enteric virus indicators.

Domestic wastewater is a source of persistent organic pollutants and pathogens to the aquatic environment, including groundwater aquifers. Wastewater contaminants include a variety of personal care products, pharmaceuticals, endocrine disrupters, bacteria, and viruses. Groundwater from 22 wells completed in a semi-confined to confined, fractured Silurian dolostone aquifer in southern Wellington County, Ontario, Canada, was analyzed for 14 organic wastewater contaminants (4 artificial sweeteners, 10 pharmaceuticals) as well as E. coli, total coliforms, and 6 human enteric viruses. Enteric viruses were detected in 8.6% of 116 samples, and at least one organic wastewater contaminant was detected in 82% of the wells (in order of decreasing detection frequency: acesulfame, ibuprofen, sulfamethoxazole, triclosan, carbamazepine, and saccharin). Virus indicator metrics [positive and negative predictive values (PPV, NPV), sensitivity, specificity] were calculated at the sample and well level for the organic wastewater compounds, E. coli, and total coliforms. Fecal bacteria were not good predictors of virus presence (PPV = 0%-8%). Of the potential chemical indicators, triclosan performed the best at the sample level (PPV = 50%, NPV = 100%), and ibuprofen performed the best at the well level (PPV = 60%, NPV = 67%); however, no samples had triclosan or ibuprofen concentrations above their practical quantification limits. Therefore, none of the compounds performed sufficiently well to be considered reliable for assessing the potential threat of enteric viruses in wastewater-impacted groundwater in this bedrock aquifer. Future studies need to evaluate the indicator potential of persistent organic wastewater contaminants in different types of aquifers, especially in fractured rock where heterogeneity is strong.IMPORTANCEAssessing the potential risk that human enteric viruses pose in groundwater aquifers used for potable water supply is complicated by several factors, including: (i) labor-intensive methods for the isolation and quantification of viruses in groundwater, (ii) the temporal variability of these viruses in domestic wastewater, and (iii) their potentially rapid transport in the subsurface, especially in fractured rock aquifers. Therefore, aquifer risk assessment would benefit from the identification of suitable proxy indicators of enteric viruses that are easier to analyze and less variable in wastewater sources. Traditional fecal indicators (e.g., E. coli and coliforms) are generally poor indicators of enteric viruses in groundwater. While many studies have examined the use of pharmaceutical and personal care products as tracers of domestic wastewater and fecal pollution in the environment, there is a paucity of data on the potential use of these chemical tracers as enteric virus indicators, especially in groundwater.

Citral and triclosan synergistically silence quorum sensing and potentiate antivirulence response in Pseudomonas aeruginosa.

Among the ESKAPE pathogens, Pseudomonas aeruginosa is an extensively notorious superbug that causes difficult-to-treat infections. Since quorum sensing (QS) directly promotes pseudomonal virulence, targeting QS circuits is a promising approach for disarming phenotypic virulence. Hence, this study scrutinizes the anti-QS, antivirulence, and anti-biofilm potential of citral (CiT; phytochemical) and triclosan (TcN; disinfectant), alone and in combination, against P. aeruginosa PAO1/PA14. The findings confirmed synergism between CiT and TcN and revealed their quorum quenching (QQ) potential. At sub-inhibitory levels, CiT-TcN combination significantly impeded pyocyanin, total bacterial protease, hemolysin, and pyochelin production alongside inhibiting biofilm formation in P. aeruginosa. Moreover, the QQ and antivirulence potential of CiT and TcN was positively correlated by molecular docking studies that predicted strong associations of the drugs with QS receptors of P. aeruginosa. Collectively, the study identifies CiT-TcN as an effective drug combination that harbors QQ, antivirulence, and anti-biofilm prospects against P. aeruginosa.

Sequential Reductive Dechlorination of Triclosan by Sediment Microbiota Harboring Organohalide-Respiring Dehalococcoidia.

Aquatic ecosystems represent a prominent reservoir of xenobiotic compounds, including triclosan (TCS), a broad-spectrum biocide extensively used in pharmaceuticals and personal care products. As a biogeochemical hotspot, the potential of aquatic sediments for the degradation of TCS remains largely unexplored. Here, we demonstrated anaerobic biotransformation of TCS in a batch microcosm established with freshwater sediment. The initial 43.4 ± 2.2 µM TCS was completely dechlorinated to diclosan, followed by subsequent conversion to 5-chloro-2-phenoxyphenol, a monochlorinated TCS (MCS) congener. Analyses of community profile and population dynamics revealed substrate-specific, temporal-growth of Dehalococcoides and Dehalogenimonas, which are organohalide-respiring bacteria (OHRB) affiliated with class Dehalococcoidia. Dehalococcoides growth was linked to the formation of diclosan but not MCS, yielding 3.6 ± 0.4 × 107 cells per µmol chloride released. A significant increase in Dehalogenimonas cells, from 1.5 ± 0.4 × 104 to 1.5 ± 0.3 × 106 mL-1, only occurred during the reductive dechlorination of diclosan to MCS. Dehalococcoidia OHRB gradually disappeared following consecutive transfers, likely due to the removal of sediment materials with strong adsorption capacity that could alleviate TCS's antimicrobial toxicity. Consequently, a solid-free, functionally stable TCS-dechlorinating consortium was not obtained. Our results provide insights into the microbial determinants controlling the environmental fate of TCS.

Triclosan Dioxygenase: A Novel Two-component Rieske Nonheme Iron Ring-hydroxylating Dioxygenase Initiates Triclosan Degradation.

The emerging contaminant triclosan (TCS) is widely distributed both in surface water and in wastewater and poses a threat to aquatic organisms and human health due to its resistance to degradation. The dioxygenase enzyme TcsAB has been speculated to perform the initial degradation of TCS, but its precise catalytic mechanism remains unclear. In this study, the function of TcsAB was elucidated using multiple biochemical and molecular biology methods. Escherichia coli BL21(DE3) heterologously expressing tcsAB from Sphingomonas sp. RD1 converted TCS to 2,4-dichlorophenol. TcsAB belongs to the group IA family of two-component Rieske nonheme iron ring-hydroxylating dioxygenases. The highest amino acid identity of TcsA and the large subunits of other dioxygenases in the same family was only 35.50%, indicating that TcsAB is a novel dioxygenase. Mutagenesis of residues near the substrate binding pocket decreased the TCS-degrading activity and narrowed the substrate spectrum, except for the TcsAF343A mutant. A meta-analysis of 1492 samples from wastewater treatment systems worldwide revealed that tcsA genes are widely distributed. This study is the first to report that the TCS-specific dioxygenase TcsAB is responsible for the initial degradation of TCS. Studying the microbial degradation mechanism of TCS is crucial for removing this pollutant from the environment.

A Unique Monitoring Method for Fecal and Sewage-Derived Chemical Pollution Utilizing International Pellet Watch Approach.

This study established a unique approach to assess fecal contamination by measuring fecal sterols, especially coprostanol (5ß-cholestanol-3ß-ol, 5ß) and cholestanol (5α-cholestan-3ß-ol, 5α) and their ratio 5ß/(5ß + 5α) alongside triclosan (TCS) and methyl-triclosan (MTC) in beached plastic pellets across 40 countries. Coprostanol concentrations ranged from 3.6 to 8190 ng/g pellet with extremely high levels in densely populated areas in African countries. The 5ß/(5ß + 5α) ratio was not affected by the difference in residence time of pellets in aquatic environments, and their spatial pattern showed a positive correlation with that of sedimentary sterols, demonstrating its reliability as an indicator of fecal contamination. Pellets from populated areas of economically developing countries, i.e., Africa and Asia, with lower coverage of wastewater treatment exhibited higher 5ß/(5ß + 5α) ratios (∼0.7) corresponding to ∼1% sewage in seawater, while pellets from developed countries, i.e., the USA, Canada, Japan, and Europe, with higher coverage of modern wastewater treatment displayed lower ratios (∼0.5), corresponding to the first contact limit. Triclosan levels were higher in developing countries (0.4-1298 ng/g pellet), whereas developed countries showed higher methyl-triclosan levels (0.5-70 ng/g pellet) due to TCS conversion during secondary treatment. However, some samples from Japan and Europe displayed higher TCS levels, suggesting contributions from combined sewage overflow (CSO). Combination of 5ß/(5ß + 5α) and MTC/TCS ratios revealed extreme fecal contamination from direct input of raw sewage due to inadequate treatment facilities in some African and South and Southeast Asian countries.

Sex-Specific and Trimester-Specific Associations of Prenatal Exposure to Bisphenols, Parabens, and Triclosan with Neonatal Birth Size and Gestational Age.

Bisphenols, parabens, and triclosan (TCS) are common endocrine disrupters used in various consumer products. These chemicals have been shown to cross the placental barrier and affect intrauterine development of fetuses. In this study, we quantified serum levels of six bisphenols, five parabens, and TCS in 483 pregnant women from southern China. Quantile-based g-computation showed that combined exposure to bisphenols, parabens, and TCS was significantly (p < 0.05) and negatively associated with birth weight (ß = -39.9, 95% CI: -73.8, -6.1), birth length (ß = -0.19, 95% CI: -0.34, -0.04), head circumference (ß = -0.13, 95% CI: -0.24, -0.02), and thoracic circumference (ß = -0.16, 95% CI: -0.29, -0.04). An inverse correlation was also identified between mixture exposure and gestational age (ß = -0.12, 95% CI: -0.24, -0.01). Bisphenol A (BPA), bisphenol Z (BPZ), bisphenol AP (BPAP), propylparaben (PrP), and TCS served as the dominant contributors to the overall effect. In subgroup analyses, male newborns were more susceptible to mixture exposure than females, whereas the exposure-outcome link was prominent among pregnant women in the first and second trimesters. More evidence is warranted to elucidate the impacts of exposure to mixtures on birth outcomes, as well as the underlying mechanisms.

Assessing silver nanoparticle and antimicrobial combinations for antibacterial activity and biofilm prevention on surgical sutures.

AIMS: To evaluate the effect of silver nanoparticles alone and in combination with Triclosan, and trans-cinnamaldehyde against Staphylococcus aureus and Escherichia coli biofilms on sutures to improve patients' outcomes. METHODS AND RESULTS: Silver nanoparticles were prepared by chemical method and characterized by UV-visible spectrophotometer and dynamic light scattering. The minimum inhibitory concentration was assessed by the Microdilution assay. The antibiofilm activity was determined using crystal violet assay. A checkerboard assay using the fractional inhibitory concentration index and time-kill curve was used to investigate the synergistic effect of silver nanoparticle combinations. The hemolytic activity was determined using an erythrocyte hemolytic assay. Our results revealed that silver nanoparticles, Triclosan, and trans-cinnamaldehyde (TCA) inhibited S.aureus and E.coli biofilms. Silver nanoparticles with TCA showed a synergistic effect (FICI values 0.35 and 0.45 against S. aureus and E. coli biofilms, respectively), and silver nanoparticles with Triclosan showed complete inhibition of S. aureus biofilm. The hemolytic activity was <2.50% for the combinations.

The first-in-class pyrazole-based dual InhA-VEGFR inhibitors towards integrated antitubercular host-directed therapy.

Several facets of the host response to tuberculosis have been tapped for clinical investigation, especially targeting angiogenesis mediated by VEGF signaling from infected macrophages. Herein, we rationalized combining the antiangiogenic effects of VEGFR-2 blockade with direct antitubercular InhA inhibition in single hybrid dual inhibitors as advantageous alternatives to the multidrug regimens. Inspired by expanded triclosans, the ether ligation of triclosan was replaced by rationalized linkers to assemble the VEGFR-2 inhibitors thematic scaffold. Accordingly, new series of 3-(p-chlorophenyl)-1-phenylpyrazole derivatives tethered to substituted ureas and their isosteres were synthesized, evaluated against Mycobacterium tuberculosis virulent cell line H37Rv, and assessed for their InhA inhibitory activities. The urea derivatives 8d and 8g exhibited the most promising antitubercular activity (MIC = 6.25 µg/mL) surpassing triclosan (MIC = 20 µg/mL) with potential InhA inhibition, thus identified as the study hits. Interestingly, both compounds inhibited VEGFR-2 at nanomolar IC50 (15.27 and 24.12 nM, respectively). Docking and molecular dynamics simulations presumed that 8d and 8g could bind to their molecular targets InhA and VEGFR-2 posing essential stable interactions shared by the reference inhibitors triclosan and sorafenib. Finally, practical LogP, Lipinski's parameters and in silico ADMET calculations highlighted their drug-likeness as novel leads in the arsenal against TB.

Efficient removal of triclosan from water through activated carbon adsorption and photodegradation processes.

This study investigated the application of adsorption with activated carbons (ACs) and photodegradation to reduce the concentration of triclosan (TCS) in aqueous solutions. Concerning adsorption, ACs (Darco, Norit, and F400) were characterised and batch experiments were performed to elucidate the effect of pH on equilibrium. The results showed that at pH = 7, the maximum adsorption capacity of TCS onto the ACs was 18.5 mg g-1 for Darco, 16.0 mg g-1 for Norit, and 15.5 mg g-1 for F400. The diffusional kinetic model allowed an adequate interpretation of the experimental data. The effective diffusivity varied and increased with the amount of TCS adsorbed, from 1.06 to 1.68 × 10-8 cm2 s-1. In the case of photodegradation, it was possible to ensure that the triclosan molecule was sensitive to UV light of 254 nm because the removal was over 80 % using UV light. The removal of TCS increased in the presence of sulfate radicals. It was possible to identify 2,4-dichlorophenol as one of the photolytic degradation products of triclosan, which does not represent an environmental hazard at low concentrations of triclosan in water. These results confirm that the use of AC Darco, Norit, and F400 and that photodegradation processes with UV light and persulfate radicals are effective in removing TCS from water, reaching concentration levels that do not constitute a risk to human health or environmental hazard. Both methods effectively eliminate pollutants with relatively easy techniques to implement.

Triclosan disturbs nitrogen removal in constructed wetlands: Responses of microbial structure and functions.

This study investigated the influence of wetland types (vertical and tidal flow constructed wetlands [CWs] [VFCW and TFCW, respectively]) and concentrations of triclosan (TCS) on the removal of pollutants (TCS and nitrogen) and microbial characteristics. The efficiency of TCS removal was significantly higher with 5 µg/L TCS (Phase B) than with 30 µg/L (Phase C) in the two CWs. The efficiencies of removal of NH4+-N and NO3--N were significantly inhibited in Phase C. Compared with the VFCW, the TFCW removed more NH4+-N at the same concentration of TCS, whereas less NO3--N was removed, and it even accumulated. Saccharimondales, an important functional genus with the highest abundance and more node connections with other genera, had a sharp decrease in relative abundance as the increasing concentrations of TCS of the two CWs conformed with its relative abundance and significantly negatively correlated with the concentration of TCS. Differentiated Roseobacter_Clade_CHAB-I-5_Lineage and Sphaerotilus were enriched in the VFCW and TFCW, respectively. The abundance of enzymes that catalyzed nitritation was significantly inhibited by TCS, whereas nitrate reductase (EC 1.7.99.4) catalyzed both denitrification and dissimilatory nitrate reduction to ammonium (DNRA), and nitrite reductase (NADH) (EC 1.7.1.15) that catalyzed DNRA comprised a larger proportion in the two CWs. Simultaneously, the abundances of two enzymes were higher in the TFCW than in the VFCW. The network analysis indicated that the main genera were promoted more by TCS in the VFCW, while inhibited in the TFCW. Moreover, the concentrations of nitrogen (NH4+-N, NO3--N, and TN) significantly positively correlated with TCS-resistant bacteria, and negatively correlated with most nitrogen-transforming bacteria with species that varied between the VFCW and TFCW. The results of this study provide a reference for the molecular biological mechanism of the simultaneous removal of nitrogen and TCS in the CWs.

Tailoring CuOx loading on CoFe2O4 nanocubes photocatalyst for superior photocatalytic degradation of triclosan pollutants under VL irradiation and toxicological evaluation.

In this study, we report the development of a novel CuOx(3 wt%)/CoFe2O4 nanocubes (NCs) photocatalyst through simple co-precipitation and wet impregnation methods for the efficient photocatalytic degradation of triclosan (TCS) pollutants. Initially, rod-shaped bare CoFe2O4 was synthesized using a simple co-precipitation technique. Subsequently, CuOx was loaded in various percentages (1, 2, and 3 wt%) onto the surface of bare CoFe2O4 nanorods (NRs) via the wet impregnation method. The synthesized materials were systematically characterized to evaluate their composition, structural and electrical characteristics. The CuOx(3 wt%)/CoFe2O4 NCs photocatalyst exhibited superior photocatalytic degradation efficiency of TCS (89.9%) compared to bare CoFe2O4 NRs (62.1 %), CuOx(1 wt%)/CoFe2O4 (80.1 %), CuOx(2 wt%)/CoFe2O4 (87.0 %) under visible light (VL) irradiation (λ ≥ 420 nm), respectively. This enhanced performance was attributed to the improved separation effectiveness of photogenerated electron (e-) and hole (h+) in CuOx(3 wt%)/CoFe2O4 NCs. Furthermore, the optimized CuOx(3 wt%)/CoFe2O4 NCs exhibited strong stability and reusability in TCS degradation, as demonstrated by three successive cycles. Genetic screening on Caenorhabditis elegans showed that CuOx(3 wt%)/CoFe2O4 NCs reduced ROS-induced oxidative stress during TCS photocatalytic degradation. ROS levels decreased at 30, 60, and 120-min intervals during TCS degradation, accompanied by improved egg hatching rates. Additionally, expression levels of stress-responsible antioxidant proteins like SOD-3GFP and HSP-16.2GFP were significantly normalized. This study demonstrates the efficiency of CuOx(3 wt%)/CoFe2O4 NCs in degrading TCS pollutants, offers insights into toxicity dynamics, and recommends its use for future environmental remediation.

Current state of knowledge of triclosan (TCS)-dependent reactive oxygen species (ROS) production.

Triclosan (TCS) is widely used in a number of industrial and personal care products. This molecule can induce reactive oxygen species (ROS) production in various cell types, which results in diverse types of cell responses. Therefore, the aim of the present study was to summarize the current state of knowledge of TCS-dependent ROS production and the influence of TCS on antioxidant enzymes and pathways. To date, the TCS mechanism of action has been widely investigated in non-mammalian organisms that may be exposed to contaminated water and soil, but there are also in vivo and in vitro studies on plants, algae, mammalians, and humans. This literature review has revealed that mammalian organisms are more resistant to TCS than non-mammalian organisms and, to obtain a toxic effect, the effective TCS dose must be significantly higher. The TCS-dependent increase in the ROS level causes damage to DNA, protein, and lipids, which together with general oxidative stress leads to cell apoptosis or necrosis and, in the case of cancer cells, faster oncogenesis and even initiation of oncogenic transformation in normal human cells. The review presents the direct and indirect TCS action through different receptor pathways.

Two-year dermal carcinogenicity bioassay of triclosan in B6C3F1 mice.

Triclosan is a widely used antimicrobial agent in personal care products, household items, medical devices, and clinical settings. Due to its extensive use, there is potential for humans in all age groups to receive lifetime exposures to triclosan, yet data on the chronic dermal toxicity/carcinogenicity of triclosan are still lacking. We evaluated the toxicity/carcinogenicity of triclosan administered dermally to B6C3F1 mice for 104 weeks. Groups of 48 male and 48 female B6C3F1 mice received dermal applications of 0, 1.25, 2.7, 5.8, or 12.5 mg triclosan/kg body weight (bw)/day in 95% ethanol, 7 days/week for 104 weeks. Vehicle control animals received 95% ethanol only; untreated, naïve control mice did not receive any treatment. There were no significant differences in survival among the groups. The highest dose of triclosan significantly decreased the body weight of mice in both sexes, but the decrease was ≤ 9%. Minimal-to-mild epidermal hyperplasia, suppurative inflammation (males only), and ulceration (males only) were observed at the application site in the treated groups, with the highest incidence occurring in the 12.5 mg triclosan/kg bw/day group. No tumors were identified at the application site. Female mice had a positive trend in the incidence of pancreatic islet adenoma. In male mice, there were positive trends in the incidences of hepatocellular carcinoma and hepatocellular adenoma or carcinoma (combined), with the increase of carcinoma being significant in the 5.8 and 12.5 mg/kg/day groups and the increase in hepatocellular adenoma or carcinoma (combined) being significant in the 2.7, 5.8, and 12.5 mg/kg/day groups.

Interleukin 1ß and interleukin 6 production in human immune cells is stimulated by the antibacterial compound Triclosan.

Triclosan (TCS) is an antimicrobial compound widely used in personal hygiene products such as mouthwash and toothpaste; and has been found in human blood, breast milk, and urine. Interleukin (IL)-6 and IL-1 beta (IL-1ß) are pro-inflammatory cytokines regulating cell growth, tissue repair, and immune function; increased levels of each have been associated with many diseases, including cancer. Previous studies showed that TCS at concentrations between 0.05 and 5 µM consistently increased the secretion of IL-1ß and IL-6 from human immune cells within 24 h of exposure. The current study demonstrates that this increase in secretion was not due simply to release of existing stores but was due to an increase in cellular production/levels (both secreted and intracellular levels) of each of these cytokines. Production of IL-1ß and IL-6 was increased by exposure to one or more concentration of TCS at each length of exposure (10 min, 30 min, 6 h, and 24 h). TCS-induced stimulation of cytokine production was shown to be dependent on the mitogen-activated protein kinase (MAPK) p44/42 (ERK 1/2). It was also shown that these TCS-induced increases in IL-1ß and IL6 production were accompanied by increased mRNA for IL-1ß and IL-6. The ability of TCS to increase production indicates that rather than activating a self-limiting process of depleting cells of already existing stores of IL-1ß or IL-6, TCS can stimulate a process that has the capacity to provide sustained production of these cytokines and thus may lead to chronic inflammation and its pathological consequences.

Cholesterol mediates the effects of single and multiple environmental phenols in urine on obesity.

BACKGROUND: Overweight and obesity are among the leading chronic diseases worldwide. Environmental phenols have been renowned as endocrine disruptors that contribute to weight changes; however, the effects of exposure to mixed phenols on obesity are not well established. METHODS: Using data from adults in National Health and Nutrition Examination Survey, this study examined the individual and combined effects of four phenols on obesity. A combination of traditional logistic regression and two mixed models (weighted quantile sum (WQS) regression and Bayesian kernel-machine regression (BKMR)) were used together to assess the role of phenols in the development of obesity. The potential mediation of cholesterol on these effects was analyzed through a parallel mediation model. RESULTS: The results demonstrated that solitary phenols except triclosan were inversely associated with obesity (P-value < 0.05). The WQS index was also negatively correlated with general obesity (ß: 0.770, 95% CI: 0.644-0.919, P-value = 0.004) and abdominal obesity (ß: 0.781, 95% CI: 0.658-0.928, P-value = 0.004). Consistently, the BKMR model demonstrated the significant joint negative effects of phenols on obesity. The parallel mediation analysis revealed that high-density lipoprotein mediated the effects of all four single phenols on obesity, whereas low-density lipoprotein only mediated the association between benzophenol-3 and obesity. Moreover, Cholesterol acts as a mediator of the association between mixed phenols and obesity. Exposure to single and mixed phenols significantly and negatively correlated with obesity. Cholesterol mediated the association of single and mixed environmental phenols with obesity. CONCLUSIONS: Assessing the potential public health risks of mixed phenols helps to incorporate this information into practical health advice and guidance.

Ecotoxicological and human health risk assessment of triclosan antibacterial agent from municipal wastewater treatment plants.

In this study, the occurrence and environmental risks related to triclosan (TCS) in the two wastewater treatment plants (WWTPs) were investigated in Isfahan, Iran. Influent and effluent samples were collected and analyzed by dispersive liquid-liquid microextraction (DLLME)-GC-MS method with derivatization. Moreover, the risk of TCS exposure was conducted for aquatic organisms (algae, crustaceans, and fishes) and humans (males and females). TCS mean concentrations in influent and effluent of WWTPs were in the range of 3.70-52.99 and 0.83-1.09 µg/L, respectively. There were also no differences in the quantity of TCS and physicochemical parameters among the two WWTPs. The mean risk quotient (RQ) for TCS was higher than 1 (in algae) with dilution factors (DFs) equal to 1 in WWTP1. Moreover, the RQ value was higher than 1 for humans based on the reference dose of MDH (RFDMDH) in WWTP1. Furthermore, TCS concentration in wastewater effluent was the influential factor in varying the risk of TCS exposure. The results of the present study showed the risk of TCS exposure from the discharge of effluent of WWTP1 was higher than WWTP2. Moreover, the results of this study may be suitable for promoting WWTP processes to completely remove micropollutants.

In vitro cytocompatibility of triclosan coated Polyglactin910 sutures.

Bioabsorbable sutures can improve the medical functions of existing non-absorbable sutures, and may produce new medical effects, and are expected to become a new generation of medical degradable materials. In this study, the cytocompatibility of triclosan coated polyglactin910 sutures (CTS-PLGA910) was analyzed and different concentrations of sutures were prepared. The effects of sutures on the cytotoxicity and cell proliferation of HUVEC were studied by CCK-8 assay. The hemolysis, total antioxidant capacity (T-AOC) activity and nitric oxide (NO) content were investigated to improve the blood compatibility of sutures. The results showed that the hemolysis rate of CTS-PLGA910 was less than 5%. After treatment on HUVEC cells for 48 and 72 h, there was no significant change in NO content in CTS-PLGA910 groups compared with the control group, while T-AOC activity and antioxidant capacity were significantly increased in medium and high dose groups. In summary, the blood compatibility and cell compatibility were significantly improved, which provided a basis for the clinical application of sutures in the future.

Cell-free hemoglobin and hemin catalyzing triclosan oxidative coupling in plasma: A novel exogenous phenolic pollutants coupling pathway.

Previous studies reported that hemoprotein CYP450 catalyzed triclosan coupling is an "uncommon" metabolic pathway that may enhance toxicity, raising concerns about its environmental and health impacts. Hemoglobin, a notable hemoprotein, can catalyze endogenous phenolic amino acid tyrosine coupling reactions. Our study explored the feasibility of these coupling reactions for exogenous phenolic pollutants in plasma. Both hemoglobin and hemin were found to catalyze triclosan coupling in the presence of H2O2. This resulted in the formation of five diTCS-2 H, two diTCS-Cl-3 H, and twelve triTCS-4 H in phosphate buffer, with a total of nineteen triclosan coupling products monitored using LC-QTOF. In plasma, five diTCS-2 H, two diTCS-Cl-3 H, and two triTCS-4 H were detected in hemoglobin-catalyzed reactions. Hemin showed a weaker catalytic effect on triclosan transformation compared to hemoglobin, likely due to hemin dimerization and oxidative degradation by H2O2, which limits its catalytic efficiency. Triclosan transformation in the human plasma-like medium still occurs with high H2O2, despite the presence of antioxidant proteins that typically inhibit such transformations. In plasma, free H2O2 was depleted within 40 minutes when 800 µM H2O2 was added, suggesting a rapid consumption of H2O2 in these reactions. Antioxidative species, or hemoglobin/hemin scavengers such as bovine serum albumin, may inhibit but not completely terminate the triclosan coupling reactions. Previous studies reported that diTCS-2 H showed higher hydrophobicity and greater endocrine-disrupting effects compared to triclosan, which further underscores the potential health risks. This study indicates that hemoglobin and heme in human plasma might significantly contribute to phenolic coupling reactions, potentially increasing health risks.

Effects of chronic triclosan exposure on nephrotoxicity and gut microbiota dysbiosis in adult mice.

Triclosan (TCS), a broad-spectrum, lipophilic, and antibacterial agent, has been commonly used in cosmetics, medical devices, and household products. The toxicity of TCS has recently become a research hotspot. Emerging evidence has shown that TCS can easily migrate to humans and animals and cause adverse effects on various target organs. However, the effects of TCS exposure on nephrotoxicity and underlying mechanisms remain unknown. The aim of the present study was to explore TCS-induced nephrotoxicity. Therefore, we establish a mouse model based on adult male mice to explore the effects of 10-week TCS exposure (50 mg/kg) on kidney. After mice were sacrificed, their blood, feces, and renal tissues were harvested for further analysis. We found that TCS treatment dramatically caused kidney structural damage, and increased blood urea nitrogen (BUN) and creatinine (Cr) expression levels, which indicated renal dysfunction. In addition, TCS exposure increased the malondialdehyde (MDA) and decreased superoxide dismutase (SOD) and total cholesterol (TCHO) expression levels, which indicated oxidative stress and lipid metabolism changes. The RNA sequencing (RNA-seq) of kidney tissue identified 221 differentially expressed genes (DEGs) enriched in 50 pathways, including drug metabolism-other enzymes, oxidative phosphorylation, glutathione metabolism, and inflammatory mediator regulation of TRP channels signaling pathways. The full-length 16S rRNA gene sequencing results showed that TCS exposure altered the community of gut microbiota, which was closely related to renal function damage. The above findings provide new insights into the mechanism of TCS-induced nephrotoxicity.