Epigallocatechin-3-gallate attenuates the sulfamethoxazole-induced immunotoxicity and reduces SMZ residues in Procambarus clarkii.

Sulfamethoxazole (SMZ) is a commonly used antibiotic in aquaculture, and its residues in water bodies pose a significant threat to aquatic organisms in the water environment. In the present study, epigallocatechin-3-gallate (EGCG), a catecholamine, was used to mitigate the immunotoxicity caused by SMZ exposure in Procambarus clarkii. EGCG reduced the apoptosis rate, which was elevated by SMZ exposure, and increased the total hemocyte count. Simultaneously, EGCG enhanced the activities of enzymes related to antibacterial and antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), lysozyme (LZM), acid phosphatase (ACP), and GSH, which were decreased following SMZ exposure. Hepatopancreatic histology confirmed that EGCG ameliorated SMZ-induced tissue damage caused by SMZ exposure. In addition to EGCG attenuating SMZ-induced immunotoxicity in crayfish, we determined that EGCG can effectively reduce SMZ residues in crayfish exposed to SMZ. In addition, at the genetic level, the expression levels of genes related to the immune response in hemocytes were disrupted after SMZ exposure, and EGCG promoted their recovery and stimulated an increase in the expression levels of metabolism-related transcripts in hemocytes. The transcriptome analysis was conducted, and "phagosome" and "apoptosis" pathways were shown to be highlighted using Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. To the best of our knowledge, this is the first study to confirm that EGCG attenuates SMZ-induced immunotoxicity in aquatic animals and reduces SMZ residues in aquatic animals exposed to SMZ. Our study contributes to the understanding of the mechanisms by which EGCG reduces the immunotoxicity of antibiotic residues in aquatic animals.

Enhanced hepatotoxicity in zebrafish due to co-exposure of microplastics and sulfamethoxazole: Insights into ROS-mediated MAPK signaling pathway regulation.

The combined pollution of microplastics (MPs) and sulfamethoxazole (SMZ) often occurs in aquatic ecosystems, posing a serious threat to animal and human health. However, little is known about the liver damage caused by the single or co-exposure of MPs and SMZ, and its specific mechanisms are still poorly understood. In this study, we investigated the effects of co-exposure to 20 µm or 80 nm MPs and SMZ in both larval and adult zebrafish models. Firstly, we observed a significant decrease in the number of hepatocytes and the liver damage in larval zebrafish worsened following co-exposure to SMZ and MPs. Additionally, the number of macrophages and neutrophils decreased, while the expression of inflammatory cytokines and antioxidant enzyme activities increased after co-exposure in larval zebrafish. Transcriptome analysis revealed significant changes in gene expression in the co-exposed groups, particularly in processes related to oxidation-reduction, inflammatory response, and the MAPK signaling pathway in the liver of adult zebrafish. Co-exposure of SMZ and MPs also promoted hepatocyte apoptosis and inhibited proliferation levels, which was associated with the translocation of Nrf2 from the cytoplasm to the nucleus and an increase in protein levels of Nrf2 and NF-kB p65 in the adult zebrafish. Furthermore, our pharmacological experiments demonstrated that inhibiting ROS and blocking the MAPK signaling pathway partially rescued the liver injury induced by co-exposure both in larval and adult zebrafish. In conclusion, our findings suggest that co-exposure to SMZ and MPs induces hepatic dysfunction through the ROS-mediated MAPK signaling pathway in zebrafish. This information provides novel insights into the potential environmental risk of MPs and hazardous pollutants co-existence in aquatic ecosystems.

Cellulose-based CoFe LDH composite as a nano-adsorbent for sulfamethoxazole and cefixime residues: Evaluation of performance, green metrics and cytotoxicity.

The increase in antibiotic residues poses a serious threat to ecological and aquatic environments, necessitating the development of cost-effective, convenient, and recyclable adsorbents. In our study, we used cellulose-based layered double hydroxide (LDH) as an efficient adsorbent and nanocarrier for both sulfamethoxazole (SMX) and cefixime (CFX) residues due to their biodegradability and biocompatibility. Chemical processes are measured according to green chemistry metrics to identify which features adhere to the principles. A GREEnness Assessment (ESA), Analytical GREEnness Preparation (AGREEprep), and Analytical Eco-Scale Assessments (ESA) were used to assess the suitability of the proposed analytical method. We extensively analyzed the synthesized CoFe LDH/cellulose before and after the adsorption processes using XRD, FTIR, and SEM. We investigated the factors affecting the adsorption process, such as pH, adsorbent dose, concentrations of SMX and CFX and time. We studied six nonlinear adsorption isotherm models at pH 5 using CoFe LDH, which showed maximum adsorption capacities (qmax) of 272.13 mg/g for SMX and 208.00 mg/g for CFX. Kinetic studies were also conducted. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was performed on Vero cells in direct contact with LDH nanocomposites to evaluate the cytotoxicity and side effects of cellulose-based CoFe LDH. The cellulose-based CoFe LDH nanocomposite demonstrated excellent cytocompatibility and less cytotoxic effects on the tested cell line. These results validate the potential use of these unique LDH-based cellulose cytocompatible biomaterials for water treatment applications. The cost of the prepared adsorbents was investigated.

Combined effects of cadmium and sulfamethoxazole on Eisenia fetida: Insights into accumulation, subcellular partitioning, biomarkers and toxicological responses.

Cadmium (Cd) and sulfamethoxazole (SMX) frequently coexist in farmlands, yet their synergistic toxicological impacts on terrestrial invertebrates remain unexplored. In this study, earthworms were exposed to artificial soils percolated with Cd (5 mg/kg), SMX (5 mg/kg) or combination of them for 7 days, followed by a 12-day elimination phase in uncontaminated soil. The uptake of Cd and SMX by the earthworms, along with their subcellular distribution, was meticulously analyzed. Additionally, a suite of biomarkers-including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and weight loss-were evaluated to assess the health status of the earthworms and the toxicological effects of the Cd and SMX mixture. Notably, the cotreatment with Cd and SMX resulted in a significantly higher weight loss in Eisenia fetida (41.25 %) compared to exposure to Cd alone (26.84 %). Moreover, the cotreatment group exhibited substantially higher concentrations of Cd in the total internal body, fraction C (cytosol), and fraction E (tissue fragments and cell membranes) in Eisenia fetida compared to Cd alone counterparts. The combined exposure also significantly elevated the SMX levels in the total body and fraction C compared with the SMX-only treated earthworms. Additionally, Eisenia fetida subjected to the combined treatment showed markedly increased activities of SOD, CAT, and MDA compared to those treated with Cd alone. The effect addition indices (EAIs), ranging from 1.00 to 2.23, unequivocally demonstrated a synergistic effect of the combined treatments. Interestingly, relocating the earthworms to clean soil did not mitigate the observed adverse effects. These findings underscore the increased risk posed by the Cd-SMX complex to terrestrial invertebrates in agricultural areas.

Biological toxicity of sulfamethoxazole in aquatic ecosystem on adult zebrafish (Danio rerio).

This study evaluated the impacts of sulfamethoxazole (SMX) on antioxidant, immune, histopathological dynamic changes, and gut microbiota of zebrafish. SMX was carried out five groups: 0 (C), 3 mg/L (T3), 6 mg/L (T6), 12 mg/L (T12), and 24 mg/L (T24), with 5 replicates per group for an 8-weeks chronic toxicity test. It was found that SMX is considered to have low toxicity to adult zebrafish. SMX with the concentration not higher than 24 mg/L has no obvious inhibitory effect on the growth of fish. Under different concentrations of SMX stress, oxidative damage and immune system disorder were caused to the liver and gill, with the 12 and 24 mg/L concentration being the most significant. At the same time, it also causes varying degrees of pathological changes in both intestinal and liver tissues. As the concentration of SMX increases, the composition and abundance of the gut microbiota in zebrafish significantly decrease.

Sulfamethoxazole stress endangers the gut health of sea cucumber (Apostichopus japonicus) and affects host metabolism.

Sulfamethoxazole (SMZ) is a frequently detected antibiotic in the environment, and there is a growing concern about its potential toxic effects on aquatic organisms. sea cucumber (Apostichopus japonicas) is a benthic invertebrate whose gut acts as a primary immune defense and serves critical protective barrier. In this study, growth performance, histology, gut microbiota, and metabolomics analyses were performed to investigate the toxic response in the intestine of sea cucumber effects caused by SMZ stress for 56 d by evaluating with different concentrations of SMZ (0, 1.2×10-3, and 1.2 mg/L). The weight gain rate of sea cucumbers under SMZ stress showed significant decrease, indicating that the growth of sea cucumbers was hindered. Analysis of the intestinal morphological features indicated that SMZ stimulation resulted in atrophy of the sea cucumber gut. In the 1.2×10-3 mg/L concentration, the thickness of muscle and mucosal layers was reduced by 12.40% and 21.39%, while in the 1.2 mg/L concentration, the reductions were 35.08% and 26.98%. The abundance and diversity of sea cucumber intestinal bacteria decreased significantly (P < 0.05) under the influence of SMZ. Notably, the intestinal bacteria of sea cucumber became homogenized with the increase in SMZ concentration, and the relative abundance of Ralstonia reached 81.64% under the stress of 1.2 mg/L concentration. The SMZ stress significantly impacted host metabolism and disrupted balance, particularly in L-threonine, L-tyrosine, neuronic acid, piperine, and docosapentaenoic acid. SMZ leads to dysregulation of metabolites, resulting in growth inhibition and potential inflammatory responses that could adversely affect the normal activities of aquatic organisms. Further metabolic pathway enrichment analyses demonstrated that impaired biosynthesis of unsaturated fatty acids and aminoacyl-tRNA biosynthesis metabolic pathway were major reasons for SMZ stress-induced intestinal bacteria dysbiosis. This research aims to provide some theoretical evidence for the ecological hazard assessment of antibiotics in water.

The effects of temperature and sulfamethoxazole on the growth and photosynthetic characteristics of Phaeodactylum tricornutum.

The misuse of antibiotics has brought potential ecological risks to marine ecosystems, especially under a changing climate. Laboratory experiments were conducted to understand the impact of rising temperatures and antibiotic sulfamethoxazole (SMX) abuse on marine diatom Phaeodactylum tricornutum. Temperatures of 21 and 24 °C were optimal for the growth and photosynthetic characteristics of P. tricornutum. When exposed to higher temperatures (≥27 °C), the growth and photosynthesis were inhibited. High concentrations of SMX (≥100 mg/L) caused rapid and acute toxicological effects on the phytoplankton. In contrast, low concentrations of SMX (1 mg/L) exhibited hormesis. When P. tricornutum was exposed to SMX at high temperatures, the stress on the phytoplankton was even more pronounced. This suggests that the combination of rising temperatures and antibiotic pollution may have a more significant negative impact on marine phytoplankton than either stressor alone. Neglecting the interaction between these stressors may lead to underestimating their combined effects on marine ecosystems.

Exposure of Danio rerio to environmental sulfamethoxazole may contribute to neurobehavioral abnormalities via gut microbiome disturbance.

The neurotoxic effects and mechanisms of low-dose and long-term sulfamethoxazole (SMZ) exposure remain unknown. This study exposed zebrafish to environmental SMZ concentrations and observed behavioral outcomes. SMZ exposure increased hyperactivity and altered the transcript levels of 17 genes associated with neurological function. It impaired intestinal function by reducing the number of intestinal goblet cells and lipid content. Metabolomic results indicated that the contents of several lipids and amino acids in the gut were altered, which might affect the expression levels of neurological function-related genes. Metagenomic results demonstrated that SMZ exposure substantially altered the composition of the gut microbiome. Zebrafish receiving a transplanted fecal microbiome from the SMZ group were also found to exhibit abnormal behavior, suggesting that the gut microbiome is an important target for SMZ exposure-induced neurobehavioral abnormalities. Multi-omics correlation analysis revealed that gut micrometabolic function was related to differential gut metabolite levels, which may affect neurological function through the gut-brain-axis. Reduced abundance of Lefsonia and Microbacterium was strongly correlated with intestinal metabolic function and may be the key bacterial genera in neurobehavioral changes. This study confirms for the first time that SMZ-induced neurotoxicity in zebrafish is closely mediated by alterations in the gut microbiome.

Transformation process and phytotoxicity of sulfamethoxazole and N4-acetyl-sulfamethoxazole in rice.

Sulfonamide antibiotics, extensively used in human and veterinary therapy, accumulate in agroecosystem soils through livestock manure and sewage irrigation. However, the interaction between sulfonamides and rice plants remains unclear. This study investigated the transformation behavior and toxicity of sulfamethoxazole (SMX) and its main metabolite, N4-acetyl-sulfamethoxazole (NASMX) in rice. SMX and NASMX were rapidly taken up by roots and translocated acropetally. NASMX showed higher accumulating capacity, with NASMX concentrations up to 20.36 ± 1.98 µg/g (roots) and 5.62 ± 1.17 µg/g (shoots), and with SMX concentrations up to 15.97 ± 2.53 µg/g (roots) and 3.22 ± 0.789 µg/g (shoots). A total of 18 intermediate transformation products of SMX were identified by nontarget screening using Orbitrap-HRMS, revealing pathways such as deamination, hydroxylation, acetylation, formylation, and glycosylation. Notably, NASMX transformed back into SMX in rice, a novel finding. Transcriptomic analysis highlights the involvements of cytochrome P450 (CYP450), acetyltransferase (ACEs) and glycosyltransferases (GTs) in these biotransformation pathways. Moreover, exposure to SMX and NASMX disrupts TCA cycle, amino acid, linoleic acid, nucleotide metabolism, and phenylpropanoid biosynthesis pathways of rice, with NASMX exerting a stronger impact on metabolic networks. These findings elucidate the sulfonamides' metabolism, phytotoxicity mechanisms, and contribute to assessing food safety and human exposure risk amid antibiotic pollution.

Revealing the response characteristics of periphyton biomass and community structure to sulfamethoxazole exposure in aquaculture water: The perspective of microbial network relationships.

The widespread application of sulfonamide antibiotics in aquaculture has raised concerns about their adverse environmental impacts. Periphyton plays a crucial role in the aquatic ecosystem. In this study, we examined sulfamethoxazole (SMX) effects on the community structure and interactions of periphyton in simulated aquaculture water. Our findings indicated that the total biomass of periphyton decreased, while the biomass of periphytic algae and the secretion of extracellular polymeric substances (EPS) increased at 0.7 × 10-3 mg/L. Under higher SMX concentrations (5 mg/L and 10 mg/L), periphyton growth was severely inhibited, the microbial community structure of periphyton were sharply altered, characterized by the cyanobacteria growth suppression and decrease in the diversity index of community. Furthermore, elevated SMX concentrations (5 mg/L and 10 mg/L) increased the ratio of negative relationships from 45.4% to 49.4%, which suggested that high SMX concentrations promoted potential competition among microbes and disrupted the microbial food webs in periphyton. The absolute abundance of sul1 and sul2 genes in T2 and T3 groups were 2-3 orders of magnitude higher than those in control group after 30 days of SMX exposure, which elevated the risk of resistance gene enrichment and dissemination in the natural environment. The study contributes to our understanding of the detrimental effects of antibiotic pollution, which can induce changes in the structure and interaction relationship of microbial communities in aquaculture water.

Effects of the aquatic pollutant sulfamethoxazole on the innate immunity and antioxidant capacity of the mud crab Scylla paramamosain.

Sulfamethoxazole (SMZ) is commonly used in aquaculture to treat bacterial infections, but its long-term residual properties in natural water can pose a direct threat to aquatic animals. This study is to investigate the effects of continuous exposure to SMZ on mud crabs (Scylla paramamosain) at four different concentrations (0, 10, 100, and 1000 ng/L) that reflect the range found in natural aquatic environments. The results confirmed that SMZ exposure reduced the expression levels of genes related to the innate immunity in mud crabs, including JAK, Astakine, TLR, and Crustin. It also stimulated oxidative stress, caused the production of reactive oxygen species and lower activities of antioxidant enzymes such as peroxidase, superoxide dismutase, catalase, and glutathione. SMZ exposure damaged the DNA of crab hemocytes and hepatopancreas tissue, and reduced the phagocytosis, ultimately leading to a decreased survival rates of mud crabs infected with Vibrio alginolyticus. These findings demonstrate that SMZ exposure has immunotoxic effects on mud crabs' innate immunity and reduces the ability to resist pathogen infections.

Self-acclimation mechanism of pyrite to sulfamethoxazole concentration in terms of degradation behavior and toxicity effects caused by reactive oxygen species.

Pyrite has been extensively tested for oxidizing contaminants via the activation of water molecule or dissolved oxygen, while the changing of oxidation species induced by contaminant's concentration has been largely underestimated. In this study, we revealed a self-acclimation mechanism of pyrite in terms of •OH conversion to 1O2 during the sulfamethoxazole (SMX) degradation process under oxic conditions. Two reaction stages of SMX degradation by pyrite were observed. The SMX concentration decreased by 70% rapidly in the first 12 h after the reaction was initiated, then, the removal rate began to decrease as the SMX concentration decreased. Importantly, •OH and O2•- were the dominant oxidizing species in stage one, while 1O2 was responsible for the further degradation of SMX in stage two. The self-acclimated mechanism of pyrite was proven to be caused by the conversion of oxidative species at the surface of pyrite. This process can overcome the shortages of •OH such as ultrashort lifetime and limited effective diffusion in the decontamination of micropollutant. Moreover, different reactive oxygen species will lead to different degradation pathways and environmental toxicity while degrading pollutants. This finding of oxidizing species' self-acclimation mechanism should be of concern when using pyrite for water treatment.

Assessing ecological responses to exposure to the antibiotic sulfamethoxazole in freshwater mesocosms.

Antibiotics are a contaminant class of worldwide concern as they are frequently detected in aquatic ecosystems. To better understand the impacts of antibiotics on aquatic ecosystems, we conducted an outdoor mesocosm experiment in which aquatic communities were exposed to different concentrations of the antibiotic sulfamethoxazole (0, 0.15, 1.5, 15 and 150 µg/L). These concentrations include mean (0.15 µg/L) and maximum detected concentrations (15 and 150 µg/L) in aquatic ecosystems worldwide. Sulfamethoxazole was applied once a week for eight consecutive weeks to 1530 L outdoor mesocosms in the Netherlands, followed by an eight-week recovery period. We evaluated phytoplankton-, bacterial- and invertebrate responses during and after sulfamethoxazole exposure and assessed impacts on organic matter decomposition. Contrary to our expectations, consistent treatment-related effects on algal and bacterial communities could not be demonstrated. In addition, sulfamethoxazole did not significantly affect zooplankton and macroinvertebrate communities. However, some effects on specific taxa were observed, with an increase in Mesostoma flatworm abundance (NOEC of <0.15 µg/L). In addition, eDNA analyses indicated negative impacts on the insects Odonata at a sulfamethoxazole concentration of 15 µg/L. Overall, environmentally relevant sulfamethoxazole concentration did not result in direct or indirect impairment of entire aquatic communities and ecological processes in our mesocosms. However, several specific macroinvertebrate taxa demonstrated significant (in)direct effects from sulfamethoxazole. Comparison of the results with the literature showed inconsistent results between studies using comparable, environmentally relevant, concentrations. Therefore, our study highlights the importance of testing the ecological impacts of pharmaceuticals (such as sulfamethoxazole) across multiple trophic levels spanning multiple aquatic communities, to fully understand its potential ecological threats.

Effects of environmentally relevant cypermethrin and sulfamethoxazole on intestinal health, microbiome, and liver metabolism in grass carp.

The incorrect use of antibiotics and pesticides poses significant risks of biological toxicity. Their simultaneous exposure could jeopardize fish health and hinder sustainable aquaculture. Here, we subjected grass carp to waterborne cypermethrin (0.65 µg/L) or/and sulfamethoxazole (0.30 µg/L) treatments for a duration of 6 weeks. We closely monitored the effects on intestinal function, the intestinal microbiome, and the liver metabolome. The results revealed that exposure to waterborne cypermethrin or/and sulfamethoxazole compromised intestinal barrier function and decreased the expression of intestinal tight junction proteins. Additionally, heightened levels of pro-inflammatory cytokines in the intestines and reduced antioxidant levels indicated systemic inflammation and oxidative stress, with more severe effects observed in the combined exposure group. 16S rRNA sequencing of intestinal tissues suggested Firmicutes play a key role in the intestinal microbiota. GC/MS metabolomics of the liver showed more differential metabolites (56) in the co-exposure group compared to cypermethrin (45) or sulfamethoxazole (32) alone, indicating greater toxicological effects with combined exposure. Our analyses also suggest that ATP-binding cassette transporters could serve as a novel endpoint for assessing the risk of pesticide and antibiotic mixtures in grass carp. In summary, this study underscores the potential ecological risks posed by antibiotics and pesticides to aquatic environments and products. It emphasizes the importance of the gut-liver axis as a comprehensive pathway for assessing the toxicity in fish exposed to environmental contaminants.

Comprehensive assessment of toxicity and environmental risk associated with sulfamethoxazole biodegradation in sulfur-mediated biological wastewater treatment.

Incomplete mineralization of sulfamethoxazole (SMX) in wastewater treatment systems poses a threat to ecological health. The toxicity and environmental risk associated with SMX biodegradation in the sulfur-mediated biological process were examined for the first time through a long-term (180 days) bioreactor study and a series of bioassays. The results indicated that the sulfur-mediated biological system was highly resistant and tolerant to SMX toxicity, as evidenced by the enrichment of sulfate-reducing bacteria (SRB), the improved microbial metabolic activity, and the excellent performance on pollutants removal under long-term SMX exposure. SMX can be effectively biodegraded by the cleavage and rearrangement of the isoxazole ring, hydrogenation and hydroxylation reactions in sulfur-mediated biological wastewater system. These biodegradation pathways effectively reduced the acute toxicity, antibacterial activity, and ecotoxicities of SMX and its biotransformation products (TPs) in the effluent of the sulfur-mediated biological system. The TPs produced via hydrogenation (TP1), hydroxylation, and isoxazole ring cleavage (TP3, TP4, TP5, TP8, and TP9) exhibited lower toxicity than SMX. Under SMX stress, although the abundance of sulfonamide resistance genes increased, the total abundance of ARGs decreased due to the extrusion of some intracellular SMX by the efflux pump genes and the inactivation of some SMX through the biodegradation process. Efflux pump and inactivation, as the main resistance mechanisms of antibiotics in the sulfur-mediated biological system, play a crucial role in microbial self-defense. The findings of this study demonstrate the great potential of the sulfur-mediated biological system in SMX removal, detoxication, and ARGs environmental risk reduction.

Application of the Aliivibrio fischeri bacterium bioassay for assessing single and mixture effects of antibiotics and copper.

The Aliivibrio fischeri bioassay was successfully applied in order to evaluate the acute effect of sulfamethoxazole (SMX), ciprofloxacin (CIP), chlortetracycline (CTC) and copper (Cu), alone or in binary, ternary, and overall mixture. The toxicity results are reported in terms of both effective concentrations, which inhibited 50% of the bacterium bioluminescence (EC50%), and in Toxic Units (TUs). The TUs were compared with predicted values obtained using the Concentration Addition model (CA). Finally, the toxicity of water extracts from a soil contaminated by the three antibiotics (7 mg Kg-1 each) in the presence/absence of copper (30 mg Kg-1) was also evaluated. Copper was the most toxic chemical (EC50: 0.78 mg L-1), followed by CTC (EC50: 3.64 mg L-1), CIP (96 mg L-1) and SMX (196 mg L-1). Comparing the TU and CA values of the mixtures, additive effects were generally found. However, a synergic action was recorded in the case of the CIP+Cu co-presence and antagonistic effects in the case of CTC+Cu and the ternary mixture (containing each antibiotic at 0.7 mg L-1), were identified. Soil water extracts did not show any toxicity, demonstrating the buffering ability of the soil to immobilize these chemicals.

Zinc attenuates sulfamethoxazole-induced lipotoxicity by reversing sulfamethoxazole-induced mitochondrial dysfunction and lysosome impairment in a freshwater teleost.

Sulfamethoxazole (SMZ) and zinc (Zn) are widespread harmful materials in aquatic ecosystems and cause toxic effects to aquatic animals under their individual exposure. Although they often co-exist in aquatic environments, little is known about their joint effects and mechanism influencing aquatic animals. Herein, SMZ induced mitochondrial and lysosomal dysfunction, inhibited autophagy flux, and induced lipotoxicity. However, SMZ-induced changes of these physiological and metabolic processes above were reversed by Zn exposure, indicating the antagonism between Zn and SMZ. SOD1-knockdown abrogated the reversing effects of Zn on mitochondria dysfunction and autophagy flux blockage induced by SMZ, suggesting that SOD1 was essential for Zn to reverse SMZ-induced mitochondria dysfunction and autophagy impairment. Our further investigation found that Zn regulated STAT3 translocation to lysosomes and mitochondria to attenuate SMZ-induced lipotoxicity, and SOD1 was required for these processes. Mechanistically, STAT3 was associated with ATP6V1 A in a coiled-coil domain-dependent manner, and pS710-STAT3-and pY753-STAT3-independent manners. Moreover, SMZ suppressed autophagic degradation of damaged mitochondria via inhibiting interaction between STAT3 and ATP6V1 A and increasing pS710-STAT3 level; SMZ impaired mitochondrial ß-oxidation via decreasing pY753-STAT3 level and STAT3 mitochondrial localization. Zn reversed these SMZ-induced effects to alleviate SMZ-induced lipotoxicity. Taken together, our data showed that SMZ impaired mitochondrial ß-oxidation and lysosomal acidification via the downregulation of SOD1, leading to lipotoxicity, and that Zn reversed SMZ-induced changes of these important biological processes and attenuated SMZ-induced lipotoxicity. Thus, our study identified previously unidentified mechanisms for the antagonistic mechanisms of Zn and SMZ on aquatic animals, which provided novel insights into the environmental risk assessments of the joint exposure between heavy metals and antibiotics in the aquatic organisms.

Effects of diclofenac, sulfamethoxazole, and wastewater from constructed wetlands on Eisenia fetida: impacts on mortality, fertility, and oxidative stress.

Soil contamination with micropollutants is an important global problem and the impact of these pollutants on living organisms cannot be underestimated. The effects of diclofenac (DCF) and sulfamethoxazole (SMX), their mixture (MIX), and wastewater containing these drugs on the mortality and reproduction of Eisenia fetida were investigated. The impact on the activities of antioxidant enzymes in earthworm cells was also assessed. Furthermore, the influence of the following parameters of the vertical flow constructed wetlands on wastewater toxicity was investigated: the dosing system, the presence of pharmaceuticals and the plants Miscanthus giganteus. The compounds and their mixture significantly affected the reproduction and mortality of earthworms. The calculated values of LC50,28 days values were 3.4 ± 0.3 mg kg-1 for DCF, 1.6 ± 0.3 mg kg-1 for SMX, and 0.9 ± 0.1 mg kg-1 for MIX. The EC50 (reproduction assay) for DCF was 1.2 ± 0.2 mg kg-1, whereas for SMX, it was 0.4 ± 0.1 mg kg-1, and for MIX, it was 0.3 ± 0.1 mg kg-1, respectively. The mixture toxicity index (MTI) was calculated to determine drug interactions. For both E. fetida mortality (MTI = 3.29) and reproduction (MTI = 3.41), the index was greater than 1, suggesting a synergistic effect of the mixture. We also observed a negative effect of wastewater (raw and treated) on mortality (32% for raw and 8% for treated wastewater) and fertility (66% and 39%, respectively) of E. fetida. It is extremely important to analyze the harmfulness of microcontaminants to organisms inhabiting natural environments, especially in the case of wastewater for irrigation of agricultural fields.

Nanoplastics enhance the intestinal damage and genotoxicity of sulfamethoxazole to medaka juveniles (Oryzias melastigma) in coastal environment.

Antibiotics and nanoplastics are widely detected in the coastal ecosystem. However, the transcriptome mechanism elucidating the effect of antibiotics and nanoplastics co-exposure on the gene expression of aquatic organisms in coastal environment is still unclear. Here, single and joint effects of sulfamethoxazole (SMX) and polystyrene nanoplastics (PS-NPs) on the intestinal health and gene expression of medaka juveniles (Oryzias melastigma), which live in coastal environment, were investigated. The SMX and PS-NPs co-exposure decreased intestinal microbiota diversity compared to the PS-NPs, and caused more adverse effect on the intestinal microbiota composition and intestinal damage compared to the SMX, indicating that PS-NPs might enhance the toxicity of SMX on the medaka intestine. The increased abundance of Proteobacteria in the intestine was observed in the co-exposure group, which might induce the intestinal epithelium damage. In addition, the differentially expressed genes (DEGs) were mainly involved in the drug metabolism-other enzymes, drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450 pathways in visceral tissue after the co-exposure. The expression of the host immune system genes (e.g., ifi30) could be associated with the increased pathogens in intestinal microbiota. This study is useful for understanding the toxicity effect of antibiotics and NPs on aquatic organisms in coastal ecosystem.

Bi(â ¢) and Ce(â £) functionalized carbon nitride photocatalyst for antibiotic degradation: Synthesis, toxicity, and mechanism investigations.

Graphite-phase carbon nitride (g-C3N4) has shown great potential for antibiotic wastewater treatment due to its unique electronic structure and corresponding to visible light. In this study, a series of Bi/Ce/g-C3N4 photocatalysts with different doping amount were developed by direct calcination method for Rhodamine B and sulfamethoxazole photocatalytic degradation. The experiment result shows that the photocatalytic performance of Bi/Ce/g-C3N4 catalysts were better than that of single component samples. Under the optimal experimental conditions, the degradation rates of RhB (20 min) and SMX (120 min) by 3Bi/Ce/g-C3N4 reached 98.3% and 70.5%, respectively. The theoretical calculation results of DFT show that after Bi and Ce doping modification, the band-gap width of g-C3N4 is reduced to 1.215 eV and carrier migration rate is greatly improved. The enhanced photocatalytic activity was mainly attributed to the capture of electrons after doping modification, which inhibition of photogenerated carriers recombination and reduced the gap width. The cyclic treatment experiment of sulfamethoxazole showed that Bi/Ce/g-C3N4 catalysts had good stability. Ecosar evaluation and leaching toxicity test showed that Bi/Ce/g-C3N4 can be safely used for wastewater treatment. This study provides a perfect strategy for modifying g-C3N4 and a new way to improve the photocatalytic performance.