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Gabapentin (GBP), an antiepileptic drug to treat epilepsy and neuropathic pain, has become an emerging pollutant in aquatic environments. Previous results suggested that GBP can cause a potential toxicity on the heart development of zebrafish but its cardiovascular effects are still not clear. In the current study, zebrafish embryos were exposed to GBP at environmental relevant concentrations (0, 0.1, 10 and 1000 µg/L) to assess its impact on cardiovascular systems during the early life stage of zebrafish. GBP exposure induced an increase in heartbeat rate and blood flow. The development of blood vessels was also affected with the vascular width significantly decreased at 10 µg/L and higher concentration of GBP. GBP exposure led to an abnormal vascular development by inhibiting the expression of relevant genes (flk1, vegfr-3, gata1, vegfα, and vegfr-2). Furthermore, GBP at 0.1 µg/L elevated the levels of reactive oxygen species and antioxidant enzyme. The vascular cell apoptosis was promoted through genes like p53, bad, and bcl2. However, these adverse effects were reversible with the antioxidant N-acetyl-L-cysteine, highlighting the crucial role of oxidative damage in GBP induced vascular toxicity. This research offers new perspectives on the adverse outcome pathways of antiepileptic drugs in non-target aquatic organisms.
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E-peroxone process is an emerging electrochemical oxidation process, based on ozone and the in-situ cathodic generation of H2O2, but the stability of cathode is one of the key restraining factors. In this study, we designed a multilayer gas diffusion electrode (GDE) decorated with a commercial hydrophobic membrane for the degradation of pyridine. It was found that a proper control of membrane pore sizes and hot-pressing temperature can significantly promote the GDE stability. Subsequently, key operational parameters of the constructed E-peroxone system were investigated, including the ozone concentration, current density, pH value, electrolyte type and initial concentration of pyridine. The degradation pathways were proposed according to six identified transformation products. The toxicity variation along the degradation progress was evaluated with microbial respiration tests and Toxicity Estimation Software Tool (T.E.S.T.) calculation and an efficient detoxification capacity of E-peroxone was observed. This research provides a theoretical basis and technical support for the development of highly efficient and stable E-peroxone system for the elimination of toxic organic contaminants.
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In aquatic ecosystems, the presence of pharmaceuticals, particularly caffeine (CAF), has been linked to wastewater discharge, hospital waste, and the disposal of expired pharmaceutical products containing CAF. Additionally, rising temperatures due to climate change are anticipated in aquatic environments. This study aimed to assess the toxicity of various CAF concentrations under current (17 °C) and projected (21 °C) temperature conditions, using the mussel Mytilus galloprovincialis as a bioindicator species. Subcellular impacts were evaluated following 28 days of exposure to four CAF concentrations (0.5; 1.0; 5.0; 10.0 µg/L) at the control temperature (17 °C). Only effects at an environmentally relevant CAF concentration (5.0 µg/L) were assessed at the highest temperature (21 °C). The overall biochemical response of mussels was evaluated using non-metric Multidimensional Scaling (MDS) and the Integrated Biomarker Response (IBR) index, while the Independent Action (IA) model was used to compare observed and predicted responses. Results showed that at 17 °C, increased CAF concentrations were associated with higher metabolism and biotransformation capacity, accompanied by cellular damage at the highest concentration. Conversely, under warming conditions (21 °C), the induction of antioxidant enzymes was observed, although insufficient to prevent cellular damage compared to the control temperature. Regarding neurotoxicity, at 17 °C, the activity of the acetylcholinesterase enzyme was inhibited up to 5.0 µg/L; however, at 10.0 µg/L, activity increased, possibly due to CAF competition for adenosine receptors. The IA model identified a synergistic response for most parameters when CAF and warming acted together, aligning with observed results, albeit with slightly lower magnitudes.
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Cafeína , Mytilus , Temperatura , Poluentes Químicos da Água , Animais , Poluentes Químicos da Água/toxicidade , Mytilus/fisiologia , Mytilus/efeitos dos fármacos , Monitoramento Ambiental , Mudança ClimáticaRESUMO
Human DNA topoisomerase 1 (Top1) is a crucial enzyme responsible for alleviating torsional stress on DNA during transcription and replication, thereby maintaining genome stability. Previous researches had found that non-working Top1 interacted extensively with chromosomal DNA in human cells. However, the reason for its retention on chromosomal DNA remained unclear. In this study, we discovered a close association between Top1 and chromosomal DNA, specifically linked to the presence of G-quadruplex (G4) structures. G4 structures, formed during transcription, trap Top1 and hinder its ability to relax neighboring DNAs. Disruption of the Top1-G4 interaction using G4 ligand relieved the inhibitory effect of G4 on Top1 activity, resulting in a further reduction of R-loop levels in cells. Additionally, the activation of Top1 through the use of a G4 ligand enhanced the toxicity of Top1 inhibitors towards cancer cells. Our study uncovers a negative regulation mechanism of human Top1 and highlights a novel pathway for activating Top1.
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DNA Topoisomerases Tipo I , Quadruplex G , Transcrição Gênica , Humanos , DNA/química , Replicação do DNA , DNA Topoisomerases Tipo I/metabolismo , Ligantes , Inibidores da Topoisomerase I/farmacologiaRESUMO
The exploration of cell response to nanotopography has attracted considerable attentions for years. This article focuses on the influence of nanotopography on the intracellular Ca2+ dynamics, the most ubiquitous but ignored second messenger. The classic titanium nanotubes (NT) were fabricated by anodization to formulate nanoporous surfaces. Firstly, the store operative calcium entry (SOCE) in endoplasmic reticulum (ER) and functional Ca2+ release-activated Ca2+ (CRAC) channels were significantly enhanced on NT surfaces that revealed by live-cell Ca2+ imaging and fluorescence resonance energy transfer (FRET) identification of orai1-stim1 connection. To investigate the potential implication of Ca2+ elevation, the dynamic cell migration trajectory was monitored by a self-made holder, which could not only be suitable for the opaque implant surface but also guarantee the focus fields identical during samples shifting. The cell migration on NT surface was more vigorous and rapid, which was correlated with higher focal adhesion proteins expression, Ca2+-dependent calpain activity and stim1 level. In conclusion, this study has confirmed the novel ER Ca2+ hemostasis pathway on nanosurfaces and its crucial role in cell migration regulation, which may help for more biofavorable implant surface design.
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Canais de Cálcio , Cálcio , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Proteínas de Membrana/metabolismo , Sinalização do CálcioRESUMO
Pharmaceutical active compounds (PhACs) have raised concerns in the last decade due to their increased consumption and inadequate elimination during discharge, resulting in their introduction into water systems and potential significant threats to non-target organisms. However, few studies have investigated the sublethal impacts of PhAC exposure on marine invertebrates. Thus, the present study aimed to assess tissue-specific responses in Mytilus galloprovincialis to sodium lauryl sulfate (SLS), salicylic acid (SA), and caffeine (CAF) (4.0 mg/L, 4.0 mg/L and 2.0 µg/L, respectively). Short-term in vitro exposures with mussel digestive gland and gill tissues were conducted and biochemical responses related to antioxidant and detoxification capacity, cellular damage and neurotoxicity were assessed. The present results clearly showed significant differences in tissue sensitivity and biochemical responses to the contaminants tested. This study highlights the suitability of filter-feeder species as valuable model organisms for studying the sublethal effects of unintended environmental exposures to PhACs.
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Mytilus , Poluentes Químicos da Água , Animais , Antioxidantes/farmacologia , Exposição Ambiental , Organismos Aquáticos/metabolismo , Preparações Farmacêuticas , Poluentes Químicos da Água/análise , Brânquias , Biomarcadores/metabolismo , Estresse OxidativoRESUMO
Surfactants are among the most common PPCPs that reach coastal systems, being often used in large quantities in cleaning products such as detergents and soap powders. Sodium lauryl sulfate (SLS) is listed in this group of emerging contaminants. Previous studies have already demonstrated the presence of SLS in aquatic environments and the negative effects on organisms living there. However, with ocean acidification and warming predictions, SLS-induced impacts may differ from those currently known. In this context, the present study aimed to reproduce environmental conditions by assessing the release of substances over a short period and to understand the influence of a rapid increase in temperature on the impacts caused. The marine bivalve Mytilus galloprovincialis was exposed to 2.0 mg/L SLS at 17 °C and 21 °C for 7 days. To assess the possible biochemical changes resulting from the exposure of mussels to SLS, a series of biomarkers related to oxidative stress/damage, detoxification, and metabolic capacity were measured. The SLS accumulation in soft tissues was low (about 0.7 ng/g) at both temperatures. The results evidenced increased metabolic activity, especially in mussels exposed to SLS at 17 °C. An increase in protein content was also observed upon exposure to SLS and increased temperature compared to controls at 17 °C. Although no effects on antioxidant enzymes were observed, protein damage was recorded, especially at 21 °C. These findings confirmed that SLS induces toxic effects and predicted climate change factors may increase the impact on M. galloprovincialis.
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Mytilus , Poluentes Químicos da Água , Animais , Temperatura , Dodecilsulfato de Sódio/toxicidade , Concentração de Íons de Hidrogênio , Água do Mar , Poluentes Químicos da Água/metabolismo , Estresse Oxidativo , Biomarcadores/metabolismoRESUMO
Polystyrene microplastics (PS MPs) and carbamazepine (CBZ) are frequently detected in freshwater ecosystems. However, the transgenerational effects of PS MPs and CBZ on the reproduction of aquatic organisms and the corresponding mechanisms are still unclear. In the present study, Daphnia magna was used to evaluate the reproductive toxicity in two consecutive generations (F0, F1). The molting and reproduction parameters, the expression of reproduction, and the toxic metabolism genes were examined after 21-day exposure. A significantly enhanced toxicity was observed in the presence of 5 µm PS MPs and CBZ. Chronic exposure results showed that the 5 µm PS MPs alone, CBZ alone, and their mixtures exerted significant reproductive toxicity of D. magna. The results of RT-qPCR showed transcripts of genes related to reproduction (cyp314, ecr-b, cut, vtg1, vtg2, dmrt93b) and toxic metabolism (cyp4, gst) were altered in both the F0 and F1. In addition, for the F0, gene transcriptional changes of reproduction were not fully translated into physiological performance, probably due to the compensatory responses caused by the low dose of PS MPs alone, CBZ alone, and their mixtures. Whereas for the F1, the trade-off between reproduction and toxic metabolism at gene levels was observed, which translated into a significant reduction in the total neonate number of F1. These findings suggest that long-term exposure to MPs and CBZ can cause serious reproduction damage to aquatic animals, which needs to be given sufficient attention.
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Microplásticos , Poluentes Químicos da Água , Animais , Plásticos , Poliestirenos , Daphnia , Ecossistema , Poluentes Químicos da Água/toxicidade , Reprodução , Carbamazepina/toxicidadeRESUMO
The comprehensive recognition of communications between bone marrow mesenchymal stem cells (bm-MSCs) and macrophages in the peri-implant microenvironment is crucial for implantation prognosis. Our previous studies have clarified the indirect influence of Ti surface topography in the osteogenic differentiation of bm-MSCs through modulating macrophage polarization. However, cell communication is commutative and multi-directional. As the immune regulatory properties of MSCs have become increasingly prominent, whether bm-MSCs could also play an immunomodulatory role on macrophages under the influence of Ti surface topography is unclear. To further illuminate the communications between bm-MSCs and macrophages, the bm-MSCs inoculated on Ti with nanoporous topography were indirectly co-cultured with macrophages, and by blocking exosome secretion or extracting the purified exosomes to induce independently, we bidirectionally confirmed that under the influence of TiO2 nanoporous topography with 80-100 nm tube diameters, bm-MSCs can exert immunomodulatory effects through exosome-mediated paracrine actions and induce M1 polarization of macrophages, adversely affecting the osteogenic microenvironment around the implant. This finding provides a reference for the optimal design of the implant surface topography for inducing better bone regeneration.
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Thyroid disrupting chemicals (TDCs) have received much attention due to their potential adverse effects on animal and human health, which calls for rapid screen assays to identify them. The triiodothyronine (T3)-induced Xenopus metamorphosis assay (TiXMA) we developed previously has been successfully applied to the detection of the TDCs disrupting thyroid hormone (TH) signaling. Here, we attempted to expand the application of the TiXMA to the screening of the TDCs interfering with the hypothalamic-pituitary-thyroid (HPT) axis. Two well-known TH synthesis inhibitors methimazole (MMI) and sodium perchlorate (SP) were employed to test the sensitivity of the TiXMA to the TDCs interfering with the HPT axis. As expected, we observed that the two chemicals concentration-dependently antagonized T3-induced morphological changes and body weight reduction of X. laevis tadpoles following 96 h-exposure, in parallel with blocked thyroid development and down-regulated tshß expression in the brain. All the data show that both MMI and SP exert inhibitory effects on T3-induced metamorphosis, indicating that the TiXMA is capable of screening the TDCs interfering with the HPT axis. In comparison with Amphibian Metamorphosis Assay (AMA), a 21-day assay for screening the TDCs interfering with the HPT axis, the TiXMA has a remarkable advantage of shorter exposure duration (96 h).
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Metimazol , Poluentes Químicos da Água , Animais , Humanos , Xenopus laevis , Metimazol/toxicidade , Metimazol/metabolismo , Poluentes Químicos da Água/toxicidade , Glândula Tireoide , Metamorfose Biológica , LarvaRESUMO
Nanotopographical cues of bone implant surface has direct influences on various cell types during the establishment of osseointegration, a prerequisite of implant bear-loading. Given the important roles of monocyte/macrophage lineage cells in bone regeneration and remodeling, the regulation of nanotopographies on macrophages and osteoclasts has arisen considerable attentions recently. However, compared to osteoblastic cells, how nanotopographies regulate macrophages and osteoclasts has not been properly summarized. In this review, the roles and interactions of macrophages, osteoclasts and osteoblasts at different stages of bone healing is firstly presented. Then, the diversity and preparation methods of nanotopographies are summarized. Special attentions are paid to the regulation characterizations of nanotopographies on macrophages polarization and osteoclast differentiation, as well as the focal adhesion-cytoskeleton mediated mechanism. Finally, an outlook is indicated of coordinating nanotopographies, macrophages and osteoclasts to achieve better osseointegration. These comprehensive discussions may not only help to guide the optimization of bone implant surface nanostructures, but also provide an enlightenment to the osteoimmune response to external implant.
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Osseointegração , Osteoclastos , Sinais (Psicologia) , Macrófagos , Contagem de LeucócitosRESUMO
Driving macrophages M2 polarization has attracted growing attention for improving osteogenesis. Here, the in situ growth of tunable gold nanoparticles (AuNPs) on titania nanotubes (TiNTs) array was realized by electrodeposition, with the guidance of TiNTs. The fabricated Au layer showed excellent biocompatibility with different osteoimmune effects. Briefly, the Au deposition on 5 and 10 V anodized TiNTs surface could induce RAW264.7 cells to M2 polarization, whereas the Au deposition on 20 V anodized TiNTs surface showed M1 polarization, as indicated by various markers determination through immunofluorescence staining, qPCR, Western blot, and ELISA. Furthermore, the osteogenic differentiation of MC3T3-E1 was significantly enhanced by the macrophages conditioned medium from the Au@10VNTs surface. The in vivo tests also confirmed denser and thicker new trabecula bone formation and more M2 macrophages infiltration both on and adjacent to the Au@10VNTs implant surface. In mechanism, the cytokine array analysis of macrophages conditioned medium from the Au@10VNTs surface revealed the upregulation of pro-healing cytokines such as IL-10 and VEGF and downregulation of pro-inflammatory cytokines such as IL-1ß and MCSF. In addition, the NF-κB pathway was significantly inhibited. In conclusion, the electrodeposition of a Au layer guided by TiNTs is a promising strategy for reducing postoperative inflammatory reactions and improving osseointegration through modulating macrophages polarization.
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Nanopartículas Metálicas , Nanotubos , Osteogênese , Ouro/farmacologia , Meios de Cultivo Condicionados/farmacologia , Galvanoplastia , Titânio/farmacologia , Titânio/metabolismo , Macrófagos/metabolismo , Citocinas/metabolismoRESUMO
Ozonation is often applied to eliminate the recalcitrant contaminants in water. During the process, toxic transformation products (TPs) can be generated mainly via the reactions with ozone and hydroxyl radicals (â¢OH). However, the toxicity difference between the TPs generated from O3 and â¢OH has not been well elucidated. In this study, we designed ozonation scenarios with different Rct values (the exposure ratio of â¢OH to O3) via varying pH values, adding a catalyst or a radical scavenger, and investigated the degradation of a popularly used antibiotic ofloxacin (OFX). The microbial oxygen uptake, the development of zebrafish embryos, and the calculation with the Toxicity Estimation Software Tool (T.E.S.T) were applied to evaluate the toxicity of TPs generated from the above reaction scenarios. The toxicity tests demonstrated that TPs formed at high-Rct conditions were less toxic than those at low-Rct conditions. Ten and eleven TPs were identified during ozonation of OFX at pH 3 and 9, respectively, based on which the different pathways were proposed. The piperazine ring's demethylation and opening occurred at both pH values, while the hydroxylation of quinolone and oxazine mainly occurred at pH 9. The study suggests that â¢OH might be more efficient in eliminating the toxicity of OFX than O3.
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Ozônio , Poluentes Químicos da Água , Purificação da Água , Animais , Radical Hidroxila , Ofloxacino/toxicidade , Oxirredução , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Peixe-ZebraRESUMO
Nebivolol (NEB), a ß-blocker frequently used to treat cardiovascular diseases, has been widely detected in aquatic environments, and can be degraded under exposure to UV radiation, leading to the formation of certain transformation products (UV-TPs). Thus, the toxic effects of NEB and its UV-TPs on aquatic organisms are of great importance for aquatic ecosystems. In the present study, the degradation pathway of NEB under UV radiation was investigated. Subsequently, zebrafish embryos/larvae were used to assess the median lethal concentration (LC50) of NEB, and to clarify the sub-lethal effects of NEB and its UV-TPs for the first time. It was found that UV radiation could reduce the toxic effects of NEB on the early development of zebrafish. Transcriptomic analysis identified the top 20 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in zebrafish larvae exposed to NEB, most of which were associated with the antioxidant, nervous, and immune systems. The number of differentially expressed genes (DEGs) in the pathways were reduced after UV radiation. Furthermore, the analysis of protein biomarkers, including CAT and GST (antioxidant response), AChE and ACh (neurotoxicity), CRP and LYS (immune response), revealed that NEB exposure reduced the activity of these biomarkers, whereas UV radiation could alleviate the effects. The present study provides initial insights into the mechanisms underlying toxic effects of NEB and the detoxification effects of UV radiation on the early development of zebrafish. It highlights the necessity of considering the toxicity of UV-TPs when evaluating the toxicity of emerging pollutants in aquatic systems.
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Poluentes Químicos da Água , Peixe-Zebra , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Ecossistema , Embrião não Mamífero , Larva , Nebivolol/metabolismo , Nebivolol/farmacologia , Transcriptoma , Raios Ultravioleta , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismoRESUMO
The biological treatment efficiency of dye wastewater using activated sludge (AS) is largely limited to the chromaticity and ecotoxicity of dyestuff. To alleviate this limitation, eleven industrial-grade disperse dyes were obtained from a fiber-dyeing factory, and for the first time, we studied the decolorization and detoxification effects of using the Pycnoporus laccase enzyme. Efficient decolorization was achieved with the following conditions: dye concentration 50 mg/L, 1-hydroxybenzotriazole (HBT) 0.15 mM, temperature 65 °C, pH 4, and laccase 0.33 U/mL. The decolorization rate of disperse dyes, ranging from 51 to 96% in this investigation, was highly dependent on the dye type, concentration, laccase loading, and HBT. The ecotoxicity of dyes was evaluated by studying the germination/growth of wheat seed as well as the respiratory rate of aerobic AS. Laccase treatment mitigated the phytotoxicity of dyes because of the higher wheat germination (e.g., increase of 38% for Black ECT 200%) and growth rate (e.g., increase of 91% for Blue 2BLN 200%). The reduced ecotoxicity of decolorized dye solution towards microorganisms was also confirmed by the finding that the oxygen uptake by aerobic AS was increased relative to that of the untreated samples (e.g., increase of 14 folds for Blue HGL 200%). In addition, the chemical oxygen demand (COD) of decolorized dye solution was slightly lower than that without decolorization during the respiratory test. The experimental results suggest that enzymatic decolorization and detoxification can be potentially used as a pretreatment method for disperse dye wastewater followed by AS treatment.
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Pycnoporus , Purificação da Água , Biodegradação Ambiental , Corantes/química , Corantes/toxicidade , Lacase/química , Águas Residuárias/química , Purificação da Água/métodosRESUMO
The cathode is the key component in the electro-peroxone process (E-Peroxone), which is popularly constructed with carbon materials. This study developed an innovative method to fabricate a cathode with waste-tire carbon (WTC) whose performance was evaluated for the degradation of tinidazole (TNZ), an antibiotic frequently detected in water. It was found that the addition of WTC in the cathode can significantly promote the yield of H2O2 and the current efficiency: around 2.7 times that of commercial carbon black at the same loading. The critical influencing factors were studied, including the current density, ozone concentration, initial pH value, chlorine ions and initial TNZ concentration. The scavenger tests demonstrated the possible involvement of â¢OH and O2â¢-. Some transformation products of TNZ were identified with UPLC-MS and the degradation pathway was proposed accordingly. These results demonstrated the potential of WTC for developing E-Peroxone cathodes.
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Ozônio , Poluentes Químicos da Água , Carbono , Cromatografia Líquida , Eletrodos , Peróxido de Hidrogênio , Oxirredução , Espectrometria de Massas em Tandem , Tinidazol , Poluentes Químicos da Água/análiseRESUMO
The titanium implant surface topography optimization for improving osseointegration has been performed for many years, whereas understanding the mechanisms of topography-induced osteogenic differentiation is still insufficient. In this study, the micro/nano-textured topography was created on titanium implant surface by acid etching and anodization. The MC3T3-E1 cells were incubated with different surfaces and the RNA sequencing technique was performed to obtain the transcriptomic information, which suggested the enrichment at "membrane" and "organelle" (GO) as well as "Calcium signal pathway" (KEGG). Consequently, a special attention was paid to the store-operated calcium entry (SOCE) mediated by Orai1 at ER-PM contact site. By fluorescence staining and western blot, it was confirmed that the Orai1 was upregulated on the micro/nano-textured titanium surface, which was correlated to the enhanced osteogenic differentiation induced by topography. Further experiments indicated that the CaMKII/ERK1/2 pathway was involved in. This research is the first time giving a comprehensive transcriptomic information of osteoblasts on micro/nano-textured topography and may provide deeper insight into the interaction between biomaterials and host.
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Osteogênese , Titânio , Materiais Biocompatíveis , Diferenciação Celular/genética , Osteoblastos , Osteogênese/genética , Titânio/farmacologiaRESUMO
Macrophages and osteoclasts are both derived from monocyte/macrophage lineage, which plays as the osteoclastic part of bone metabolism. Although they are regulated by bone implant surface nanoarchitecture and involved in osseointegration, the beneath mechanism has not been simultaneously analyzed in a given surface model and their communication with osteoblasts is also blurring. Here, the effect of implant surface topography on monocyte/macrophage lineage osteoclastogenesis and the subsequent effect on osteogenesis are systematically investigated. The nanoporous surface is fabricated on titanium implant by etching and anodizing to get the nanotubes structure. The early bone formation around implant is significantly accelerated by the nanoporous surface in vivo. Meanwhile, the macrophage recruitment and osteoclast formation are increased and decreased respectively. Mechanistically, the integrin mediated FAK phosphorylation and its downstream MAPK pathway (p-p38) are significantly downregulated by the nanoporous surface, which account for the inhibition of osteoclastogenesis. In addition, the nanoporous surface can alleviate the inhibition of osteoclasts on osteogenesis by changing the secretion of clastokines, and accelerate bone regeneration by macrophage cytokine profiles. In conclusion, these data indicate that physical topography of implant surface is a critical factor modulating monocyte/macrophage lineage commitment, which provides theoretical guidance and mechanism basis for promoting osseointegration by coupling the osteogenesis and osteoclastogenesis.
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Despite extensive investigation on the toxicity of microplastics (MPs), an emerging global concern, little is known about the combined toxicity of MPs and co-occurring pollutants in aquatic environments. In this study, the combined toxicity of polystyrene MPs and sulfamethoxazole (SMZ) antibiotics was explored in zebrafish embryos in terms of the developmental, physiological, and endocrine toxicities. Exposure to PS and SMZ induced mortality (rate: 25.0 ± 7.5%) and malformation (rate: 20~35%) at multiple regions and stages of zebrafish development. Physiological toxicity was also induced as shown by the significant decrease in fetal movement (by 31.1~37.0%) and swimming frequency (by 26.9~36.8%) and the increase in heartbeat rate (by 19.0~20.9%). Finally, PS and SMZ exposure also induced extensive endocrine toxicities in zebrafish as confirmed by increases in various biomarkers including vitellogenin, 17ß-estradiol, testosterone, and triiodothyronine. The combination index showed that antagonistic effects were present between PS and SMZ toxicity, which slightly decreased their combined toxicity. This study aims to further understand the combined toxicity of MPs and co-occurring pollutants in aquatic environments.