RESUMO
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.
Assuntos
Dioxigenases , Triclosan , Triclosan/metabolismo , Dioxigenases/metabolismo , Dioxigenases/genética , Biodegradação Ambiental , Escherichia coli , Sphingomonas/enzimologia , Sphingomonas/metabolismo , Poluentes Químicos da Água/metabolismoRESUMO
Triclosan (TCS), a hydrophobic antibacterial agent, is extensive application in daily life. Despite a low biodegradability rate, its hydrophobicity results in its accumulation in waste-activated sludge (WAS) during domestic and industrial wastewater treatment. While anaerobic digestion is the foremost strategy for WAS treatment, limited research has explored the interphase migration behavior and impacts of TCS on WAS degradation during anaerobic digestion. This study revealed TCS migration between solid- and liquid-phase in WAS digestion. The solid-liquid distribution coefficients of TCS were negative for proteins and polysaccharides and positive for ammonium. High TCS levels promoted volatile-fatty-acid accumulation and reduced methane production. Enzyme activity tests and functional prediction indicated that TCS increased enzyme activity associated with acid production, in contrast to the inhibition of key methanogenic enzymes. The findings of the TCS migration behavior and its impacts on WAS anaerobic digestion provide an in-depth understanding of the evolution of enhanced TCS-removing technology.
Assuntos
Metano , Esgotos , Triclosan , Triclosan/farmacologia , Triclosan/metabolismo , Anaerobiose , Metano/metabolismo , Biodegradação Ambiental , Ácidos Graxos Voláteis/metabolismo , Reatores Biológicos , Poluentes Químicos da Água/metabolismo , Eliminação de Resíduos Líquidos/métodosRESUMO
Triclosan is a widely used antibacterial agent and disinfectant, and its overuse endangered ecological safety and human health. Therefore, reducing residual TCS concentrations in the environment is an urgent issue. Bacillus sp. DL4, an aerobic bacterium with TCS biodegradability, was isolated from pharmaceutical wastewater samples. Response surface methodology (RSM) and artificial neural network (ANN) were carried out to optimize and verify the different condition variables, and the optimal growth conditions of strain DL4 were obtained (35 °C, initial pH 7.31, and 5% v/v). After 48 h of cultivation under the optimal conditions, the removal efficiency of strain DL4 on TCS was 95.89 ± 0.68%, which was consistent with the predicted values from RSM and ANN models. In addition, higher R2 value and lower MSE and ADD values indicated that the ANN model had a stronger predictive capability than the RSM model. Whole genome sequencing results showed that many functional genes were annotated in metabolic pathways related to TCS degradation (e.g., amino acid metabolism, xenobiotics biodegradation and metabolism, carbohydrate metabolism). Main intermediate metabolites were identified during the biodegradation process by liquid chromatography-mass spectrometry (LC-MS), and a possible pathway was hypothesized based on the metabolites. Overall, this study provides a theoretical foundation for the characterization and mechanism of TCS biodegradation in the environment by Bacillus sp. DL4.
Assuntos
Bacillus , Biodegradação Ambiental , Triclosan , Bacillus/metabolismo , Triclosan/metabolismo , Cinética , Poluentes Químicos da Água/metabolismo , Águas Residuárias/microbiologia , Redes Neurais de ComputaçãoRESUMO
Triclosan (TCS) is a biocide widely used in personal care and medicinal products. TCS persists in sediments and has been detected worldwide, making sediments a vital route of TCS exposure to aquatic organisms. This experiment explored the bioaccumulation and toxicological effects of TCS-contaminated sediment. The study revealed that the half-life of TCS in the sediment-water system was 21.52 days. Exposure of Clarias magur juveniles to 0.4 and 0.8 mg kg-1 TCS-spiked sediment resulted in high Biota-Sediment Accumulation Factor (BSAF) with the highest bioaccumulation in the liver (29.62-73.61 mg kg-1), followed by gill (9.22-17.57 mg kg-1), kidney (5.04-9.76 mg kg-1), muscle (2.63-4.87 mg kg-1) and brain (1.53-3.20 mg kg-1). Furthermore, a concentration-dependent increase in oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) was documented during 45 days of exposure in gill, liver, kidney, muscle, and brain tissues of exposed fish. A similar increasing trend was also recorded for liver transaminase enzymes such as glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) during the experimental period compared to control. Serum biochemical analysis revealed a significant time and concentration-dependent increase in serum glucose, serum GOT, and serum GPT, while serum total protein and albumin decreased significantly during exposure. These findings demonstrate high bioaccumulative and toxic nature of TCS in fish, promoting multiple physiological and biochemical dysfunctions through sediment exposure. The study underscores the urgent need for strengthened regulations and robust monitoring of triclosan across various environmental matrices, including sediment, to mitigate the detrimental impacts of TCS effectively.
Assuntos
Biomarcadores , Peixes-Gato , Sedimentos Geológicos , Glutationa Transferase , Triclosan , Poluentes Químicos da Água , Triclosan/toxicidade , Triclosan/metabolismo , Animais , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismo , Sedimentos Geológicos/química , Peixes-Gato/metabolismo , Biomarcadores/metabolismo , Glutationa Transferase/metabolismo , Brânquias/metabolismo , Brânquias/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Catalase/metabolismo , Superóxido Dismutase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Água Doce , Rim/metabolismo , Rim/efeitos dos fármacos , Monitoramento Ambiental/métodosRESUMO
Emerging organic contaminants present in the environment can be biodegraded in anodic biofilms of microbial fuel cells (MFCs). However, there is a notable gap existing in deducing the degradation mechanism, intermediate products, and the microbial communities involved in degradation of broad-spectrum antibiotic such as triclosan (TCS). Herein, the possible degradation of TCS is explored using TCS acclimatized biofilms in MFCs. 95% of 5 mgL-1 TCS are been biodegraded within 84 h with a chemical oxygen demand (COD) reduction of 62% in an acclimatized-MFC (A-MFC). The degradation of TCS resulted in 8 intermediate products including 2,4 -dichlorophenol which gets further mineralized within the system. Concurrently, the 16S rRNA V3-V4 sequencing revealed that there is a large shift in microbial communities after TCS acclimatization and MFC operation. Moreover, 30 dominant bacterial species (relative intensity >1%) are identified in the biofilm in which Sulfuricurvum kujiense, Halomonas phosphatis, Proteiniphilum acetatigens, and Azoarcus indigens significantly contribute to dihydroxylation, ring cleavage and dechlorination of TCS. Additionally, the MFC was able to produce 818 ± 20 mV voltage output with a maximum power density of 766.44 mWm-2. The antibacterial activity tests revealed that the biotoxicity of TCS drastically reduced in the MFC effluent, signifying the non-toxic nature of the degraded products. Hence, this work provides a proof-of-concept strategy for sustainable mitigation of TCS in wastewaters with enhanced bioelectricity generation.
Assuntos
Bactérias , Biodegradação Ambiental , Fontes de Energia Bioelétrica , Biofilmes , Triclosan , Triclosan/metabolismo , Bactérias/metabolismo , Poluentes Químicos da Água/metabolismo , RNA Ribossômico 16S , Clorofenóis/metabolismo , CatáliseRESUMO
Triclosan (TCS), a biocide used in various day-to-day products, has been associated with several toxic effects in aquatic organisms. In the present study, biochemical and hematological alterations were evaluated after 14 d (sublethal) exposure of tap water (control), acetone (solvent control), 5, 10, 20, and 50 µg/L (environmentally relevant concentrations) TCS to the embryos/hatchlings of Cirrhinus mrigala, a major freshwater carp distributed in tropic and sub-tropical areas of Asia. A concentration-dependent increase in the content of urea and protein carbonyl, while a decrease in the total protein, glucose, cholesterol, triglycerides, uric acid, and bilirubin was observed after the exposure. Hematological analysis revealed a decrease in the total erythrocyte count, hemoglobin, and partial pressure of oxygen, while there was an increase in the total leucocyte count, carbon dioxide, and partial pressure of carbon dioxide and serum electrolytes. Comet assay demonstrates a concentration-dependent increase in tail length, tail moment, olive tail moment, and percent tail DNA. An amino acid analyzer showed a TCS-dose-dependent increase in various amino acids. Sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis revealed different proteins ranging from 6.5 to 200 kDa, demonstrating TCS-induced upregulation. Fourier transform infrared spectra analysis exhibited a decline in peak area percents with an increase in the concentration of TCS in water. Curve fitting of amide I (1,700-1600 cm-1) showed a decline in α-helix and turns and an increase in ß-sheets. Nuclear magnetic resonance study also revealed concentration-dependent alterations in the metabolites after 14 d exposure. TCS caused alterations in the biomolecules and heamatological parameters of fish, raising the possibility that small amounts of TCS may change the species richness in natural aquatic habitats. In addition, consuming TCS-contaminated fish may have detrimental effects on human health. Consequently, there is a need for the proper utilisation and disposal of this hazardous compound in legitimate quantities.
Assuntos
Carpas , Cyprinidae , Triclosan , Poluentes Químicos da Água , Animais , Humanos , Triclosan/toxicidade , Triclosan/metabolismo , Dióxido de Carbono/metabolismo , Cyprinidae/metabolismo , Água/metabolismo , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismoRESUMO
Triclosan (TCS) is a wide-spectrum antibacterial agent that is found in various water environments. It has been reported to have estrogenic effects. However, the impact of TCS exposure on the reproductive system of zebrafish (Danio rerio) throughout their life cycle is not well understood. In this study, zebrafish fertilized eggs were exposed to 0, 10, and 50 µg/L TCS for 120 days. The study investigated the effects of TCS exposure on brain and testis coefficients, the expression of genes related to the hypothalamus-pituitary-gonadal (HPG) axis, hormone levels, vitellogenin (VTG) content, histopathological sections, and performed RNA sequencing of male zebrafish. The results revealed that life cycle TCS exposure had significant effects on zebrafish reproductive parameters. It increased the testis coefficient, while decreasing the brain coefficient. TCS exposure also led to a decrease in mature spermatozoa and altered the expression of genes related to the HPG axis. Furthermore, TCS disrupted the balance of sex hormone levels and increased VTG content of male zebrafish. Transcriptome sequencing analysis indicated that TCS affected reproductive endocrine related pathways, including PPAR signaling pathway, cell cycle, GnRH signaling pathway, steroid biosynthesis, cytokine-cytokine receptor interaction, and steroid hormone biosynthesis. Protein-protein interaction (PPI) network analysis confirmed the enrichment of hub genes in these pathways, including bub1bb, ccnb1, cdc20, cdk1, mcm2, mcm5, mcm6, plk1, and ttk in the brain, as well as fabp1b.1, fabp2, fabp6, ccr7, cxcl11.8, hsd11b2, and hsd3b1 in the testis. This study sheds light on the reproductive endocrine-disrupting mechanisms of life cycle exposure to TCS.
Assuntos
Triclosan , Poluentes Químicos da Água , Animais , Masculino , Peixe-Zebra/metabolismo , Triclosan/toxicidade , Triclosan/metabolismo , Poluentes Químicos da Água/toxicidade , Estágios do Ciclo de Vida , Hormônios Esteroides Gonadais/metabolismo , Esteroides/metabolismoRESUMO
Although triclosan has been ubiquitously detected in aquatic environment and is known to have various adverse effects to fish, details on its uptake, bioconcentration, and elimination in fish tissues are still limited. This study investigated the uptake and elimination toxicokinetics, bioconcentration, and biotransformation potential of triclosan in Nile tilapia (Oreochromis niloticus) exposed to environmentally-relevant concentrations under semi-static regimes for 7 days. For toxicokinetics, triclosan reached a plateau concentration within 5-days of exposure, and decreased to stable concentration within 5 days of elimination. Approximately 50 % of triclosan was excreted by fish through feces, and up to 29 % of triclosan was excreted through the biliary excretion. For fish exposed to 200 ng·L-1, 2000 ng·L-1, and 20,000 ng·L-1, the bioconcentration factors (log BCFs) of triclosan in fish tissues obeyed similar order: bile ≈ intestine > gonad ≈ stomach > liver > kidney ≈ gill > skin ≈ plasma > brain > muscle. The log BCFs of triclosan in fish tissues are approximately maintained constants, no matter what triclosan concentrations in exposure water. Seven biotransformation products of triclosan, involved in both phase I and phase II metabolism, were identified in this study, which were produced through hydroxylation, bond cleavages, dichlorination, and sulfation pathways. Metabolite of triclosan-O-sulfate was detected in all tissues of tilapia, and more toxic product of 2,4-dichlorophenol was also found in intestine, gonad, and bile of tilapia. Meanwhile, two metabolites of 2,4-dichlorophenol-O-sulfate and monohydroxy-triclosan-O-sulfate were firstly discovered in the skin, liver, gill, intestine, gonad, and bile of tilapia in this study. These findings highlight the importance of considering triclosan biotransformation products in ecological assessment. They also provide a scientific basis for health risk evaluation of triclosan to humans, who are associated with dietary exposure through ingesting fish.
Assuntos
Clorofenóis , Ciclídeos , Tilápia , Triclosan , Poluentes Químicos da Água , Animais , Humanos , Tilápia/metabolismo , Triclosan/toxicidade , Triclosan/metabolismo , Distribuição Tecidual , Ciclídeos/metabolismo , Biotransformação , Sulfatos/metabolismo , Poluentes Químicos da Água/análiseRESUMO
Triclosan (TCS), recognized as an endocrine disruptor, has raised significant concerns due to its widespread use and potential health risks. To explore the impact of TCS on lipid metabolism, both larval and adult zebrafish were subjected to acute and chronic exposure to TCS. Through analyzes of biochemical and physiological markers, as well as Oil Red O (ORO) and hematoxylin and eosin (H&E) staining, our investigation revealed that TCS exposure induced hepatic and intestinal lipid accumulation in larval and adult zebrafish, leading to structural damage and inflammatory responses in these tissues. The strong affinity of TCS with PPARγ and subsequent pathway activation indicate that PPARγ pathway plays a crucial role in TCS-induced lipid buildup. Furthermore, we observed a decrease in m6A-RNA methylation levels in the TCS-treated group, which attributed to the increased activity of the demethylase FTO and concurrent suppression of the methyltransferase METTL3 gene expression by TCS. The alteration in methylation dynamics is identified as a potential underlying mechanism behind TCS-induced lipid accumulation. To address this concern, we explored the impact of folic acid-a methyl donor for m6A-RNA methylation-on lipid accumulation in zebrafish. Remarkably, folic acid administration partially alleviated lipid accumulation by restoring m6A-RNA methylation. This restoration, in turn, contributed to a reduction in inflammatory damage observed in both the liver and intestines. Additionally, folic acid partially mitigates the up-regulation of PPARγ and related genes induced by TCS. These findings carry substantial implications for understanding the adverse effects of environmental pollutants such as TCS. They also emphasize the promising potential of folic acid as a therapeutic intervention to alleviate disturbances in lipid metabolism induced by environmental pollutants.
Assuntos
Adenina/análogos & derivados , Triclosan , Poluentes Químicos da Água , Animais , Triclosan/toxicidade , Triclosan/metabolismo , Peixe-Zebra/metabolismo , Metilação de RNA , PPAR gama/genética , PPAR gama/metabolismo , Poluentes Químicos da Água/toxicidade , Fígado , Lipídeos , Intestinos , Ácido Fólico/metabolismo , Ácido Fólico/farmacologiaRESUMO
Triclosan (TCS), a prevalent contaminant in aquatic ecosystems, has been identified as a potential threat to both aquatic biota and human health. Despite its widespread presence, research into the immunotoxic effects of TCS on aquatic organisms is limited, and the underlying mechanisms driving these effects remain largely unexplored. Herein, we investigated the developmental and immune toxicities of environmentally relevant concentrations of TCS in zebrafish, characterized by morphological anomalies, histopathological impairments, and fluctuations in cytological differentiation and biomarkers following both acute (from 6 to 72/120 hpf) and chronic exposure periods (from 30 to 100 dpf). Specifically, acute exposure to TCS resulted in a significant increase in innate immune cells, contrasted by a marked decrease in T cells. Furthermore, we observed that TCS exposure elicited oxidative stress and a reduction in global m6A levels, alongside abnormal expressions within the m6A modification enzyme system in zebrafish larvae. Molecular docking studies suggested that mettl3 might be a target molecule for TCS interaction. Intriguingly, the knock-down of mettl3 mirrored the effects of TCS exposure, adversely impacting the growth and development of zebrafish, as well as the differentiation of innate immune cells. These results provide insights into the molecular basis of TCS-induced immunotoxicity through m6A-RNA epigenetic modification and aid in assessing its ecological risks, informing strategies for disease prevention linked to environmental contaminants.
Assuntos
Triclosan , Poluentes Químicos da Água , Animais , Humanos , Triclosan/toxicidade , Triclosan/metabolismo , Peixe-Zebra/metabolismo , Regulação para Baixo , Metilação de RNA , Ecossistema , Simulação de Acoplamento Molecular , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismoRESUMO
In recent years, nanoplastics (NPs) and triclosan (TCS, a pharmaceutical and personal care product) have emerged as environmental pollution issues, and their combined presence has raised widespread concern regarding potential risks to organisms. However, the combined toxicity and mechanisms of NPs and TCS remain unclear. In this study, we investigated the toxic effects of polystyrene NPs and TCS and their mechanisms on KGN cells, a human ovarian granulosa cell line. We exposed KGN cells to NPs (150⯵g/mL) and TCS (15⯵M) alone or together for 24â¯hours. Co-exposure significantly reduced cell viability. Compared with exposure to NPs or TCS alone, co-exposure increased reactive oxygen species (ROS) production. Interestingly, co-exposure to NPs and TCS produced synergistic effects. We examined the activity of superoxide dismutase (SOD) and catalase (CAT), two antioxidant enzymes; it was significantly decreased after co-exposure. We also noted an increase in the lipid oxidation product malondialdehyde (MDA) after co-exposure. Furthermore, co-exposure to NPs and TCS had a more detrimental effect on mitochondrial function than the individual treatments. Co-exposure activated the NRF2-KEAP1-HO-1 antioxidant stress pathway. Surprisingly, the expression of SESTRIN2, an antioxidant protein, was inhibited by co-exposure treatments. Co-exposure to NPs and TCS significantly increased the autophagy-related proteins LC3B-II and LC3B-â and decreased P62. Moreover, co-exposure enhanced CASPASE-3 expression and inhibited the BCL-2/BAX ratio. In summary, our study revealed the synergistic toxic effects of NPs and TCS in vitro exposure. Our findings provide insight into the toxic mechanisms associated with co-exposure to NPs and TCS to KGN cells by inducing oxidative stress, activations of the NRF2-KEAP1-HO-1 pathway, autophagy, and apoptosis.
Assuntos
Triclosan , Feminino , Humanos , Espécies Reativas de Oxigênio/metabolismo , Triclosan/toxicidade , Triclosan/metabolismo , Antioxidantes/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Microplásticos/metabolismo , Poliestirenos/toxicidade , Poliestirenos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Células da Granulosa/metabolismoRESUMO
Triclosan has been extensively used as a preservative in cosmetics and personal care products. However, its accumulation represents a real environmental threat. Thus, its phytotoxic impact needs more consideration. Our study was conducted to highlight the phytotoxic effect of triclosan on the growth, ROS homeostasis, and detoxification metabolism of two different plant species i.e., legumes (Glycine max) and grass (Avena sativa). Moreover, we investigated the potentiality of plant growth-promoting bacteria (ST-PGPB) in mitigating the phytotoxic effect of triclosan. Triclosan induced biomass (fresh and dry weights) reduction in both plants, but to a higher extent in oats. This decline was associated with a noticeable increment in the oxidative damage (e.g., MDA and H2O2) and detoxification metabolites such as metallothionein (MTC), phytochelatins (PCs), and glutathione-S-transferase (GST). This elevation was associated with a remarkable reduction in both enzymatic and non-enzymatic antioxidants. On the other hand, the bioactive strain of ST-PGPB, Salinicoccus sp. JzA1 significantly alleviated the harmful effect of triclosan on both soybean and oat plants by enhancing their biomass, photosynthesis, as well as levels of minerals (K, Ca, P, Mn, and Zn). In parallel, a striking quenching in oxidative damage and an obvious improvement in non-enzymatic (polyphenols, tocopherols, flavonoids) and enzymatic antioxidants were observed. Furthermore, Salinicoccus sp. JzA1 augmented the detoxification metabolism by enhancing the levels of phytochelatins, metallothionein, and glutathione-S-transferase (GST) activity in a species-specific manner which is more apparent in soybean rather than in oat plants. To this end, stress mitigating impact of Salinicoccus sp. JzA1 provides a basis to improve the resilience of crop species under cosmetics and personal care products toxicity.
Assuntos
Cosméticos , Triclosan , Avena/metabolismo , Triclosan/metabolismo , Triclosan/toxicidade , Glycine max , Espécies Reativas de Oxigênio/metabolismo , Fitoquelatinas/metabolismo , Peróxido de Hidrogênio/metabolismo , Antioxidantes/metabolismo , Estresse Oxidativo , Plantas/metabolismo , Homeostase , Cosméticos/metabolismo , Cosméticos/farmacologia , Metalotioneína/metabolismo , Transferases/metabolismoRESUMO
As a potential environmental obesogen, triclosan (TCS) carries inherent risks of inducing obesity and metabolic disorders. However, the underlying molecular mechanisms behind the lipid metabolism disorder induced by TCS have remained elusive. Through a fusion of transcriptomics and microRNA target prediction, we hypothesize that miR-101a as a responsive miRNA to TCS exposure in zebrafish, playing a central role in disturbing lipid homeostasis. As an evidence, TCS exposure triggers a reduction in miR-10a expression that accompanied by elevation of genes linked to regulation of lipid homeostasis. Through precision-controlled interventions involving miRNA expression modulation, we discovered that inhibition of miR-101a enhanced expression of its target genes implicated in lipid homeostasis, subsequently triggering excessive fat accumulation. Meanwhile, the overexpression of miR-101a acts as a protective mechanism, counteracting the lipid metabolism disorder induced by TCS in the larvae. Notably, the combination of short-chain fatty acids (SCFAs) emerged as a potential remedy to alleviate TCS-induced lipid accumulation partially by counteracting the decline in miR-101a expression induced by TCS. These revelations provide insight into a prospective molecular framework underlying TCS-triggered lipid metabolism disorders, thereby paving the way for pre-emptive strategies in combating the ramifications of TCS pollution.
Assuntos
Transtornos do Metabolismo dos Lipídeos , MicroRNAs , Triclosan , Animais , Triclosan/toxicidade , Triclosan/metabolismo , Peixe-Zebra/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ácidos Graxos Voláteis/metabolismoRESUMO
Since European regulators restricted the use of bacteriocidic triclosan (TCS), alternatives for TCS are emerging. Recently, TCS has been shown to reprogram immune metabolism, trigger the NLRP3 inflammasome, and subsequently the release of IL-1ß in human macrophages, but data on substitutes is scarce. Hence, we aimed to examine the effects of TCS compared to its alternatives at the molecular level in human macrophages. LPS-stimulated THP-1 macrophages were exposed to TCS or its substitutes, including benzalkonium chloride, benzethonium chloride, chloroxylenol, chlorhexidine (CHX) and cetylpyridinium chloride, with the inhibitory concentration (IC10-value) of cell viability to decipher their mode of action. TCS induced the release of the pro-inflammatory cytokine TNF and high level of IL-1ß, suggesting the activation of the NLRP3-inflammasome, which was confirmed by non-apparent IL-1ß under the NLRP3-inhibitor MCC950 treatment d. While IL-6 release was reduced in all treatments, the alternative CHX completely abolished the release of all investigated cytokines. To unravel the underlying molecular mechanisms, we used untargeted LC-MS/MS-based proteomics. TCS and CHX showed the strongest cellular response at the protein and signalling pathway level, whereby pathways related to metabolism, translation, cellular stress and migration were mainly affected but to different proposed modes of action. TCS inhibited mitochondrial electron transfer and affected phagocytosis. In contrast, in CHX-treated cells, the translation was arrested due to stress conditions, resulting in the formation of stress granules. Mitochondrial (e.g. ATP5F1D, ATP5PB, UQCRQ) and ribosomal (e.g. RPL10, RPL35, RPS23) proteins were revealed as putative key drivers. Furthermore, we have demonstrated the formation of podosomes by CHX, potentially involved in ECM degradation. Our results exhibit modulation of the immune response in macrophages by TCS and its substitutes and illuminated underlying molecular effects. These results illustrate critical processes involved in the modulation of macrophages' immune response by TCS and its alternatives, providing information essential for hazard assessment.
Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Triclosan , Humanos , Inflamassomos/metabolismo , Triclosan/metabolismo , Clorexidina/farmacologia , Cromatografia Líquida , Espectrometria de Massas em Tandem , Macrófagos , Interleucina-1beta/metabolismo , Citocinas/metabolismo , ImunidadeRESUMO
Vermicomposting represents an environmentally friendly method for the treatment of various types of biowastes, including sewage sludge (SS), as documented in numerous studies. However, there are few papers providing insights into the mechanisms and toxicity effects involved in SS vermicomposting to present a comprehensive overview of the process. In this work, the vermiremediation of SS containing various micropollutants, including pharmaceuticals, personal care products, endocrine disruptors, and per/polyfluoroalkyl substances, was studied. Two SSs originating from different wastewater treatment plants (WWTP1 and WWTP2) were mixed with a bulking agent, moistened straw, at ratios of 0, 25, 50, and 75% SS. Eisenia andrei earthworms were introduced into the mixtures, and after six weeks, the resulting materials were subjected to various types of chemical and toxicological analyses, including conventional assays (mortality, weight) as well as tissue- and cell-level assays, such as malondialdehyde production, cytotoxicity tests and gene expression assays. Through the vermiremediation process significant removal of diclofenac (90%), metoprolol (88%), telmisartan (62%), and triclosan (81%) was achieved. Although the concentrations of micropollutants were substantially different in the original SS samples, the micropollutants vermiaccumulated to a similar extent over the incubation period. The earthworms substantially eliminated the present bacterial populations, especially in the 75% SS treatments, in which the average declines were 90 and 79% for WWTP1 and WWTP2, respectively. To the best of our knowledge, this is the first study to investigate the vermiremediation of such a large group of micropollutants in real SS samples and provide a thorough evaluation of the effect of SS on earthworms at tissue and cellular level.
Assuntos
Oligoquetos , Triclosan , Animais , Esgotos/química , Solo/química , Triclosan/análise , Triclosan/metabolismoRESUMO
The broadly utilized biocide triclosan (TCS) is continuously discharged in water compartments worldwide, where it is detected at concentrations of ng-µg/L. Given its lipophilicity and bioaccumulation, TCS is considered potentially harmful to human and environmental health and also as a potential endocrine disruptor (ED) in different species. In aquatic organisms, TCS can induce a variety of effects: however, little information is available on its possible impact on invertebrate development. Early larval stages of the marine bivalve Mytilus galloprovincialis have been shown to be sensitive to environmental concentrations of a number of emerging contaminants, including EDs. In this work, the effects of TCS were first evaluated in the 48 h larval assay in a wide concentration range (0.001-1,000 µg/L). TCS significantly affected normal development of D-veligers (LOEC = 0.1 µg/L; EC50 = 236.1 µg/L). At selected concentrations, the mechanism of action of TCS was investigated. TCS modulated transcription of different genes involved in shell mineralization, endocrine signaling, ceramide metabolism, and biotransformation, depending on larval stage (24 and 48 h post-fertilization-hpf) and concentration (1 and 10 µg/L). At 48 hpf and 10 µg/L TCS, calcein staining revealed alterations in CaCO3 deposition, and polarized light microscopy showed the absence of shell birefringence due to the mineralized phase. Observations by scanning electron microscopy highlighted a variety of defects in shell formation from concentrations as low as 0.1 µg/L. The results indicate that TCS, at environmental exposure levels, can act as a developmental disruptor in early mussel larvae mainly by interfering with the processes of biomineralization.
Assuntos
Desinfetantes , Mytilus , Triclosan , Poluentes Químicos da Água , Animais , Humanos , Triclosan/toxicidade , Triclosan/metabolismo , Desinfetantes/toxicidade , Mytilus/metabolismo , Larva , Poluentes Químicos da Água/metabolismoRESUMO
Triclosan (TCS), a broad-spectrum antibacterial chemical, has been extensively used in personal daily care items, household commodities, and clinical medications; therefore, humans are at risk of being exposed to TCS in their daily lives. This chemical also accumulated in food chains, and potential risks were associated with its metabolism in vivo. The aim of this study was to investigate the difference in metabolic profile of TCS by hepatic P450 enzymes and extrahepatic P450s, and also identify chemical structures of its metabolites. The results showed that RLM mediated the hydroxylation and cleavage of the ether moiety of TCS, resulting in phenolic metabolites that are more polar than the parent compound, including 4-chlorocatechol, 2,4-dichlorophenol and monohydroxylated triclosan. The major metabolite of CYP1A1 and CYP1B1 mediated TCS metabolism is 4-chlorochol. We also performed molecular docking experiments to investigate possible binding modes of TCS in the active sites of human CYP1B1, CYP1A1, and CYP3A4. In addition to in vitro experiments, we further examined the cytotoxic effects of TCS on HepG2 cells expressing hepatic P450 and MCF-7/1B1 cells expressing CYP1B1. It exhibited significant cytotoxicity on HepG2, MCF-10A and MCF-7/1B1 cells, with IC50 values of 70 ± 10 µM, 20 ± 10 µM and 60 ± 20 µM, respectively. The co-incubation of TCS with glutathione (GSH) as a chemopreventive agent could reduce the cytotoxicity of TCS in vitro. The chemopreventive effects of GSH might be ascribed to the promotion of TCS efflux mediated by membrane transporter MRP1 and also its antioxidant property, which partially neutralized the oxidative stress of TCS on mammalian cells. This study contributed to our understanding of the relationship between the P450 metabolism and the toxicity of TCS. It also had implications for the use of specific chemopreventive agents against the toxicity of TCS.
Assuntos
Triclosan , Animais , Humanos , Triclosan/toxicidade , Triclosan/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Simulação de Acoplamento Molecular , Sistema Enzimático do Citocromo P-450/metabolismo , Fenóis , Quimioprevenção , Mamíferos/metabolismoRESUMO
A previous study reported positive associations of maternal urinary concentrations of triclosan, a synthetic phenol with widespread exposure in the general population, with placental DNA methylation of male fetuses. Given the high number of comparisons performed in -omic research, further studies were needed to validate and extend on these findings. Using a cohort of male and female fetuses with repeated maternal urine samples to assess exposure, we studied the associations between triclosan and placental DNA methylation. We assessed triclosan concentrations in two pools of 21 urine samples collected among 395 women from the SEPAGES cohort. We used Infinium Methylation EPIC arrays to measure DNA methylation in placental biopsies collected at delivery. We performed a candidate study restricted to a set of candidate CpGs (n = 500) identified in a previous work as well as an exploratory epigenome-wide association study to investigate the associations between triclosan and differentially methylated probes and regions. Analyses were conducted on the whole population and stratified by child's sex. Mediation analysis was performed to test whether heterogeneity of placental tissue may mediate the observed associations. In the candidate approach, we confirmed 18 triclosan-associated genes when both sexes were considered. After stratification for child's sex, triclosan was associated with 72 genes in females and three in males. Most of the associations were positive and several CpGs mapped to imprinted genes: FBRSL1, KCNQ1, RHOBTB3, and SMOC1. A mediation effect by placental tissue heterogeneity was identified for most of the observed associations. In the exploratory analysis, we identified a few isolated associations in the sex-stratified analysis. In line with a previous study on male placentas, our approach revealed several positive associations between triclosan exposure and placental DNA methylation. Several identified loci mapped to imprinted genes.
Assuntos
Efeitos Tardios da Exposição Pré-Natal , Triclosan , Criança , Humanos , Feminino , Gravidez , Masculino , Placenta/metabolismo , Metilação de DNA , Triclosan/toxicidade , Triclosan/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismoRESUMO
As a commonly used antibacterial agent in daily consumer products, triclosan (TCS) has attracted significant attention due to its potential environmental risks. In this study, we investigated the toxic effects of TCS exposure (1.4 µM) on heart development in zebrafish embryos. Our findings revealed that TCS exposure caused significant cardiac dysfunction, characterized by pericardial edema, malformations in the heart structure, and a slow heart rate. Additionally, TCS exposure induced oxidative damage and abnormal apoptosis in heart cells through the up-regulation of ß-adrenergic receptor (ß-AR) signaling pathway genes (adrb1, adrb2a, arrb2b), similar to the effects induced by ß-AR agonists. Notably, the adverse effects of TCS exposure were alleviated by ß-AR antagonists. Using high-throughput transcriptome miRNA sequencing and targeted miRNA screening, we focused on miR-133b, which targets adrb1 and was down-regulated by TCS exposure, as a potential contributor to TCS-induced cardiotoxicity. Inhibition of miR-133b produced similar toxic effects as TCS exposure, while overexpression of miR-133b down-regulated the ß-AR signaling pathway and rescued heart defects caused by TCS. In summary, our findings provide new insights into the mechanisms underlying the cardiotoxic effects of TCS. We suggest that targeting the ß-AR pathway and miR-133b may be effective strategies for pharmacotherapy in cardiotoxicity induced by environmental pollutants such as TCS.
Assuntos
MicroRNAs , Triclosan , Animais , Triclosan/toxicidade , Triclosan/metabolismo , Peixe-Zebra/metabolismo , Cardiotoxicidade , MicroRNAs/genética , Transdução de Sinais , Receptores Adrenérgicos beta/metabolismoRESUMO
Since a mixed state of environmental contaminants, including microplastics (MPs), heavy metals, pharmaceuticals, and personal care products (PPCPs), exists in aquatic ecosystems, it is necessary to evaluate not only the adverse effects of exposure to a single stressor but to combined stressors. In this study, we exposed the freshwater water flea Daphnia magna to 2⯵m MPs and triclosan (TCS), one of PPCPs, for 48â¯h to investigate the synergistic toxic consequences of simultaneous exposure to both pollutants. We measured in vivo endpoints, antioxidant responses, multixenobiotic resistance (MXR) activity, and autophagy-related protein expression via the PI3K/Akt/mTOR and MAPK signaling pathways. While MPs single exposure did not show toxic effects in water fleas, simultaneous exposure to TCS and MPs was associated with significantly greater deleterious effects in the form of increased mortality and alterations in antioxidant enzymatic activities compared with water fleas exposed to TCS alone. In addition, MXR inhibition was confirmed by measurement of the expression of P-glycoproteins and multidrug-resistance proteins in MPs-exposed groups, which led to the accumulation of TCS. Overall, these results suggest that simultaneous exposure to MPs and TCS resulted in higher TCS accumulation via MXR inhibition, leading to synergistic toxic effects such as autophagy in D. magna.