ABSTRACT
Low molecular weight chitosan selenium nanoparticles (LCS-SeNPs), a biologically active compound derived from selenium polysaccharides, have demonstrated potential in addressing obesity. However, the mechanism through which LCS-SeNPs alleviate high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) remains unclear. Our results elucidated that LCS-SeNPs significantly inhibited fat accumulation and markedly improved the intestinal barrier by increasing mucus secretion from goblet cells. Moreover, LCS-SeNPs reshaped intestinal flora composition by increasing the abundance of mucus-associated microbiota (Bifidobacterium, Akkermansia, and Muribaculaceae_unclassified) and decreasing the abundance of obesity-contributed bacterium (Anaerotruncus, Lachnoclostridium, and Proteus). The modulation of intestinal microbiota by LCS-SeNPs influenced several metabolic pathways, including bile acid secretion, purine metabolites, and tryptophan derivation. Meanwhile, glycocholic acid and tauro-beta-muricholic acid were significantly reduced in the LCS-SeNP group. Our study suggests the crucial role of intestinal microbiota composition and metabolism, providing a new theoretical foundation for utilizing selenium polysaccharides in the intervention of HFD-induced NAFLD.
ABSTRACT
Recent decades have witnessed substantial interest in extracellular vesicles (EVs) due to their crucial role in intercellular communication across various biological processes. Among these, plant-derived exosome-like Nanoparticles (ELNs) have rapidly gained recognition as highly promising candidates. ELNs, characterized by diverse sources, cost-effective production, and straightforward isolation, present a viable option for preventing and treating numerous diseases. Furthermore, ELNs hold significant potential as carriers for natural or engineered drugs, enhancing their attractiveness and drawing considerable attention in science and medicine. However, translating ELNs into clinical applications poses several challenges. This study explores these challenges and offers critical insights into potential research directions. Additionally, it provides a forward-looking analysis of the industrial prospects for ELNs. With their broad applications and remarkable potential, ELNs stand at the forefront of biomedical innovation, poised to revolutionize disease management and drug delivery paradigms in the coming years.
ABSTRACT
Epoxiconazole (EPX) is a broad-spectrum fungicide extensively used in agricultural pest control. Emerging evidence suggests that EPX can adversely affect different endpoints in non-target organisms. Here, the toxicity of EPX was assessed using earlier developmental stage of zebrafish as a model to investigate its effects on metabolism and intestinal microbiota after 21 days of exposure. Our findings indicated that EPX exposure resulted in physiological alterations in juvenile zebrafish, including increase in triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and glycose (Glu). Nile red staining demonstrated enhanced lipid accumulation in juvenile, accompanied by a marked upregulation in the expression of genes associated with TG synthesis. Moreover, EPX led to alterations in amino acids and carnitines levels in 21 dpf (days post fertilization) zebrafish. We also observed that EPX disrupted intestinal barrier function in juvenile zebrafish, manifested by decreasing mucus secretion and changing in genes related to tight junctions. Moreover, for a more comprehensive analysis of the intestinal microbiota in 21 dpf zebrafish, the intestine tissues were dissected under a microscope for 16S rRNA sequencing analysis. The results revealed that EPX altered the structure and abundance of intestinal microflora in zebrafish, including decreased alpha diversity indices and shifted in bacteria at phylum and genus levels. Notably, the correlation analysis demonstrated strong associations between alterations in various pathogenic bacterial genera and levels of amino acids and carnitines. Overall, these findings confirm that the fungicide EPX promotes metabolic disorders and alterations in the intestinal micro-environment in 21 dpf zebrafish, shedding light on the toxicologic effects of chemicals to aquatic organisms during the development stage.
Subject(s)
Fungicides, Industrial , Gastrointestinal Microbiome , Homeostasis , Triazoles , Zebrafish , Animals , Gastrointestinal Microbiome/drug effects , Triazoles/toxicity , Triazoles/pharmacology , Homeostasis/drug effects , Fungicides, Industrial/toxicity , RNA, Ribosomal, 16S/genetics , Epoxy CompoundsABSTRACT
The coexistence of heavy metals and pesticides poses a critical challenge in agricultural ecosystems. Traditional toxicity assessments often focus only on the individual impacts of either pesticides or heavy metals. Here, the untargeted metabolomics and 16 S rRNA sequencing were used to assess the individual and combined effects of cadmium (Cd) and triazophos (TRI) on hook snout carps (Opsariichthys bidens). Cd caused much more serious impacts on hepatic metabolism and gut microbiota than those in TRI. Combined Cd and TRI exposure synergistically affected hepatic metabolism, causing mitochondrial dysfunction and even oxidative damage. Simultaneously, 16 S rRNA sequencing highlighted significant variations in the composition and abundance of gut microbiota. A noteworthy connection emerged between these distinct microbiota profiles and disruptions in energy metabolism, ultimately leading to disorders in metabolites. These findings enhanced the understanding of risks posed by heavy metals and pesticides, providing insights for better environmental risk assessments of aquatic organisms.
Subject(s)
Cadmium , Organothiophosphates , Triazoles , Water Pollutants, Chemical , Animals , Cadmium/toxicity , Water Pollutants, Chemical/toxicity , Triazoles/toxicity , Organothiophosphates/toxicity , Liver/drug effects , Liver/metabolism , Gastrointestinal Microbiome/drug effects , RNA, Ribosomal, 16S/genetics , Metabolomics , Pesticides/toxicity , MultiomicsABSTRACT
With the wide application of bromuconazole (BRO), a kind of triazole fungicide, the environmental problems caused by BRO have been paid more and more attention. In this study, adult male zebrafish were exposed to environmental related concentration and the maximum non-lethal concentration for zebrafish larvae (0,50 ng/L and 7.5 mg/L) for 7 days, respectively. Zebrafish exposed to BRO exhibited a significant reduction in body length and an increase in fatness index, indicating adverse physiological changes. Notably, the exposed zebrafish showed enlarged heart ventricular volumes and thinner heart walls. Transcriptome analysis of heart samples showed that BRO exposure mainly affected pathways related to cardiac energy metabolism. In addition, the amount of ATP in the heart tissue was correspondingly reduced, and the expression levels of genes related to controlling ion balance and myosin synthesis in the heart were also altered. The study extended its findings to the rat cardiomyocytes (H9C2), where similar cardiotoxic effects including changes in transcription of genes related to energy metabolism and heart function were also observed, suggesting a potential universal mechanism of BRO-induced cardiotoxicity. In a doxorubicin (DOX) induced larval zebrafish heart failure model, the expression of lymphoid enhancer-binding factor 1(LEF1), a key gene in the Wnt/ß-catenin signaling pathway, was significantly increased in larval zebrafish and adult fish heart tissues and cardiomyocytes, suggesting that LEF1 might play an important role in BRO-induced cardiotoxicity. Taken together, BRO exposure could interfere with cardiac function and metabolic capacity by abnormal activation the expression of LEF1. The study emphasized the urgent need for monitoring and regulating BRO due to its harmful effects on the hearts of aquatic organisms.
Subject(s)
Heart , Triazoles , Water Pollutants, Chemical , Zebrafish , Animals , Male , Cardiotoxicity , Fungicides, Industrial/toxicity , Heart/drug effects , Lymphoid Enhancer-Binding Factor 1/genetics , Lymphoid Enhancer-Binding Factor 1/metabolism , Triazoles/toxicity , Up-Regulation , Water Pollutants, Chemical/toxicityABSTRACT
Inflammatory bowel diseases (IBDs) refer to multifaceted disorders in the intestinal microenvironment and microbiota homeostasis. In view of the broad bioactivity and high compatibility of polyphenols, there is considerable interest in developing a polyphenol-based collaborative platform to remodel the IBD microenvironment and regulate microbiota. Here, we demonstrated the coordination assembly of nanostructured polyphenols to modify probiotics and simultaneously deliver drugs for IBD treatment. Inspired by the distinctive structure of tannic acid (TA), we fabricated nanostructured pBDT-TA by using a self-polymerizable aromatic dithiol (BDT) and TA, which exhibited excellent antioxidant and anti-inflammatory capability in vitro. We thus coated pBDT-TA and sodium alginate (SA) to the surface of Escherichia coli Nissle 1917 layer by layer to construct the collaborative platform EcN@SA-pBDT-TA. The modified probiotics showed improved resistance to oxidative and inflammatory stress, which resulted in superior colon accumulation and retention in IBD model mice. Further, EcN@SA-pBDT-TA could alleviate dextran sulfate sodium (DSS)-induced colitis by controlling the inflammatory response, repairing intestinal barriers, and modulating gut microbiota. Importantly, EcN@SA-pBDT-TA-mediated IBD drug delivery could achieve an improved therapeutic effect in DSS model mice. Given the availability and functionality of polyphenol and prebiotics, we expected that nanostructured polyphenol-modified probiotics provided a solution to develop a collaborative platform for IBD treatment.
Subject(s)
Inflammatory Bowel Diseases , Nanoparticles , Polyphenols , Probiotics , Tannins , Animals , Probiotics/pharmacology , Probiotics/chemistry , Probiotics/administration & dosage , Polyphenols/chemistry , Polyphenols/pharmacology , Mice , Nanoparticles/chemistry , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/therapy , Tannins/chemistry , Tannins/pharmacology , Mice, Inbred C57BL , Escherichia coli/drug effects , Dextran Sulfate/chemistry , Alginates/chemistry , Alginates/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , Antioxidants/pharmacologyABSTRACT
Chlorothalonil (CTL), an organochloride fungicide applied for decades worldwide, has been found to be present in various matrixes and even accumulates in humans or other mammals through the food chain. Its high residue and diffusion in the environment have severely affected food security and public health. More and more research has considered CTL as a possible toxin to environmental non-target organisms, via influencing multiple systems such as metabolic, developmental, endocrine, genetic, and reproductive pathways. Aquatic organisms and amphibians are the most vulnerable species to CTL exposure, especially during the early period of development. Under experimental conditions, CTL can also have toxic effects on rodents and other non-target organisms. As for humans, CTL exposure is most often reported to be relevant to allergic reactions to the skin and eyes. We hope that this review will improve our understanding of the hazards and risks that CTL poses to non-target organisms and find a strategy for rational use.
Subject(s)
Fungicides, Industrial , Nitriles , Animals , Humans , Aquatic Organisms/drug effects , Environmental Pollutants/toxicity , Fungicides, Industrial/toxicity , Nitriles/toxicity , Risk AssessmentABSTRACT
Doxorubicin (DOX) is a commonly used anthracycline in cancer chemotherapy. The clinical application of DOX is constrained by its cardiotoxicity. Myricetin (MYR) is a natural flavonoid widely present in many plants with antioxidant and anti-inflammatory properties. However, MYR's beneficial effects and mechanisms in alleviating DOX-induced cardiotoxicity (DIC) remain unknown. C57BL/6 mice were injected with 15â¯mg/kg of DOX to establish the DIC, and MYR solutions were administrated by gavage to investigate its cardioprotective potentials. Histopathological analysis, physiological indicators assessment, transcriptomics analysis, and RT-qPCR were used to elucidate the potential mechanism of MYR in DIC treatment. MYR reduced cardiac injury produced by DOX, decreased levels of cTnI, AST, LDH, and BNP, and improved myocardial injury and fibrosis. MYR effectively prevented DOX-induced oxidative stress, such as lowered MDA levels and elevated SOD, CAT, and GSH activities. MYR effectively suppressed NLRP3 and ASC gene expression levels to inhibit pyroptosis while regulating Caspase1 and Bax levels to reduce cardiac cell apoptosis. According to the transcriptomic analysis, glucose and fatty acid metabolism were associated with differential gene expression. KEGG pathway analysis revealed differential gene enrichment in PPAR and AMPK pathways, among others. Following validation, MYR was found to alleviate DIC by regulating glycolipid metabolism and AMPK pathway-related genes. Our findings demonstrated that MYR could mitigate DIC by regulating the processes of oxidative stress, apoptosis, and pyroptosis. MYR is critical in improving DOX-induced myocardial energy metabolism abnormalities mediated by the AMPK signaling pathway. In conclusion, MYR holds promise as a therapeutic strategy for DIC.
Subject(s)
Cardiotoxicity , Doxorubicin , Flavonoids , Gene Expression Profiling , Mice, Inbred C57BL , Oxidative Stress , Animals , Doxorubicin/toxicity , Flavonoids/pharmacology , Cardiotoxicity/prevention & control , Male , Mice , Oxidative Stress/drug effects , Gene Expression Profiling/methods , Cardiotonic Agents/pharmacology , Apoptosis/drug effects , Transcriptome/drug effectsABSTRACT
The compound 6PPD is widely acknowledged for its antioxidative properties; however, concerns regarding its impact on aquatic organisms have spurred comprehensive investigations. In our study, we advanced our comprehension by revealing that exposure to 6PPD could induce cardiac dysfunction, myocardial injury and DNA damage in adult zebrafish. Furthermore, our exploration unveiled that the exposure of cardiomyocytes to 6PPD resulted in apoptosis and mitochondrial injury, as corroborated by analyses using transmission electron microscopy and flow cytometry. Significantly, our study demonstrated the activation of the autophagy pathway in both the heart of zebrafish and cardiomyocytes, as substantiated by transmission electron microscopy and immunofluorescent techniques. Importantly, the increased the expression of P62 in the heart and cardiomyocytes suggested an inhibition of the autophagic process. The reduction in autophagy flux was also verified through in vivo experiments involving the infection of mCherry-GFP-LC3. We further identified that the fusion of autophagosomes and lysosomes was impaired in the 6PPD treatment group. In summary, our findings indicated that the impaired fusion of autophagosomes and lysosomes hampered the autophagic degradation process, leading to apoptosis and ultimately resulting in cardiac dysfunction and myocardial injury. This study discovered the crucial role of the autophagy pathway in regulating 6PPD-induced cardiotoxicity. SYNOPSIS: 6PPD exposure inhibited the autophagic degradation process and induced mitochondrial injury and apoptosis in the heart of adult zebrafish.
Subject(s)
Apoptosis , Autophagy , Mitochondria , Myocytes, Cardiac , Zebrafish , Animals , Autophagy/drug effects , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Apoptosis/drug effects , Mitochondria/drug effects , Lysosomes/drug effects , Lysosomes/metabolism , DNA Damage , Heart/drug effectsABSTRACT
Inflammatory bowel disease (IBD) is a chronic inflammatory disease characterized by intestinal barrier dysfunction, inflammatory synergistic effects and excessive tissue injury. Gallic acid (GA) is renowned for its remarkable biological activity, encompassing anti-inflammatory and antioxidant properties. However, the underlying mechanisms by which GA protects against intestinal inflammation have not been fully elucidated. The aim of this study is to investigate the effect of GA on the inflammation of a lipopolysaccharide (LPS)-stimulated human colon carcinoma cell line (Caco-2) and on the intestinal barrier dysfunction, and explore the underlying molecular mechanism involved. Our findings demonstrate that 5â µg/mL GA restores the downregulation of the mRNA and protein levels of Claudin-1, Occludin, and ZO-1 and decreases the expressions of inflammatory factors such as IL-6, IL-1ß and TNF-α induced by LPS. In addition, GA exhibits a protective effect by reducing the LPS-enhanced early and late apoptotic ratios, downregulating the mRNA levels of pro-apoptotic factors ( Bax, Bad, Caspase-3, Caspase-8, and Caspase-9), and upregulating the mRNA levels of anti-apoptotic factor Bcl-2 in Caco-2 cells. GA also reduces the levels of reactive oxygen species increased by LPS and restores the activity of antioxidant enzymes, namely, superoxide dismutase and catalase, as well as the level of glutathione. More importantly, GA exerts its anti-inflammatory effects by inhibiting the LPS-induced phosphorylation of key signaling molecules in the NF-κB/MAPK pathway, including p65, IκB-α, p38, JNK, and ERK, in Caco-2 cells. Overall, our findings show that GA increases the expressions of tight junction proteins, reduces cell apoptosis, relieves oxidative stress and suppresses the activation of the NF-κB/MAPK pathway to reduce LPS-induced intestinal inflammation in Caco-2 cells, indicating that GA has potential as a therapeutic agent for intestinal inflammation.
Subject(s)
Apoptosis , Gallic Acid , Inflammation , Lipopolysaccharides , NF-kappa B , Humans , Gallic Acid/pharmacology , Caco-2 Cells , Lipopolysaccharides/toxicity , NF-kappa B/metabolism , Inflammation/metabolism , Inflammation/chemically induced , Inflammation/drug therapy , Apoptosis/drug effects , MAP Kinase Signaling System/drug effects , Anti-Inflammatory Agents/pharmacology , Signal Transduction/drug effects , Reactive Oxygen Species/metabolism , Oxidative Stress/drug effectsABSTRACT
Epoxiconazole (EPX) is a triazole fungicide, which has been widely used in pest control of cereal crops. However, its extensive use has led to concerning levels of residue in water bodies, posing substantial risks to aquatic life. In this study, we characterized the toxicological effects of EPX on 6-month-old male and female zebrafish at 70 and 700 µg/L, respectively. The results revealed that EPX exposure markedly increased both body length and weight in zebrafish of both sexes, consequently elevating their condition factor. Besides, EPX exposure resulted in notable alterations in hepatic histopathology. These changes included loosened hepatocyte structure, ballooning degeneration, nucleolysis, and disappearance of cell line, with male zebrafish exhibiting more severe damage. High concentration of EPX also significantly increased hepatic lipid accumulation in male zebrafish, as well as increased hepatic triglyceride (TG) levels. Correspondingly, there was a notable alteration in the transcription of genes including cyp51, hmgcr, and PPAR-γ, which associated with cholesterol and lipid metabolism. Interestingly, with the hepatic transcriptomic analysis, high concentration of EPX produced 195 upregulated and 107 downregulated differential expression genes. Both KEGG and GO analyses identified significant enrichment of these genes in lipid and amino acid metabolism pathways. Notably, some key genes involved in the steroid synthesis pathway were marked upregulated. In addition, molecular docking study confirmed that EPX could bind CYP51 protein well (â³G = -7.7 kcal/mol). Taken together, these findings demonstrated the multiple toxic effects of EPX on adult zebrafish.
Subject(s)
Epoxy Compounds , Lipid Metabolism , Zebrafish , Animals , Male , Female , Zebrafish/genetics , Zebrafish/metabolism , Molecular Docking Simulation , Triazoles/toxicity , Gene Expression Profiling , LipidsABSTRACT
BACKGROUND: Plant-derived extracellular vesicles (PDEVs) are membrane vesicles characterized by a phospholipid bilayer as the basic skeleton that is wrapped by various functional components of proteins and nucleic acids. An increasing number of studies have confirmed that PDEVs can be a potential treatment of inflammatory bowel disease (IBD) and can, to some extent, compensate for the limitations of existing therapies. AIM OF REVIEW: This review summarizes the recent advances and potential mechanisms underlying PDEVs obtained from different sources to alleviate IBD. In addition, the review discusses the possible applications and challenges of PDEVs, providing a theoretical basis for exploring novel and practical therapeutic strategies for IBD. KEY SCIENTIFIC CONCEPTS OF REVIEW: In IBD, the crosstalk mechanism of PDEVs may regulate the intestinal microenvironment homeostasis, especially immune responses, the intestinal barrier, and the gut microbiota. In addition, drug loading enhances the therapeutic potential of PDEVs, particularly regarding improved tissue targeting and stability. In the future, not only immunotherapy based on PDEVs may be an effective treatment for IBD, but also the intestinal barrier and intestinal microbiota will be a new direction for the treatment of IBD.
ABSTRACT
As a fungicide with the characteristics of high effectiveness, internal absorption and broad spectrum, imazalil is widely used to prevent and treat in fruits and vegetables. Here, pregnant C57BL/6 mice were exposed to imazalil at dietary levels of 0, 0.025, and 0.25 through drinking water during pregnancy and lactation. We then analyzed the phenotype, metabolome, and expression of related genes and proteins in the livers of mice. There was a marked decrease in the body and liver weights of male offspring mice after maternal imazalil exposure, while this effect on the dam and female offspring was slight. Metabolomics analyses revealed that imazalil significantly altered the metabolite composition of liver samples from both dams and offspring. The preliminary results of the analysis indicated that glucolipid metabolism was the pathway most significantly affected by imazalil. We performed a coabundance association analysis of metabolites with significant changes in the pathway of glycolipid metabolism, and IMZ altered the networks of both dams and offspring compared with the network in control mice, especially in male offspring. The hepatic triglyceride, non-esterified fatty acid and glucose levels were increased significantly in the dams but decreased significantly in male offspring after maternal imazalil exposure. Furthermore, the expression levels of genes associated with glycolipid metabolism and m6A RNA methylation were significantly affected by maternal intake of imazalil. Imazalil-induced glucolipid metabolism disturbance was highly correlated with m6A RNA methylation. In conclusion, maternal imazalil exposure resulted in glucolipid metabolism disturbance and abnormal m6A RNA methylation in the livers of dams and offspring mice. We expected that the information acquired in this study will provide novel evidence for understanding the effect of maternal imazalil exposure on potential health risks.
Subject(s)
Imidazoles , Liver , RNA Methylation , Pregnancy , Mice , Male , Female , Animals , Mice, Inbred C57BL , Liver/metabolism , Glycolipids/metabolismABSTRACT
As an efficient triazole fungicide, prothioconazole (PTC) is widely used for the prevention and control of plant fungal pathogens. It was reported that the residues of PTC and prothioconazole-desthio (PTC-d) have been detected in the environment and crops, and the effects of PTC-d may be higher than that of PTC. Currently, PTC and PTC-d have been proven to induce hepatic metabolic disorders. However, their toxic effects on cellular bile acid (BA) and glucolipid metabolism remain unknown. In this study, HepG2 cells were exposed to 1-500 µM of PTC or PTC-d. High concentrations of PTC and PTC-d were found to induce cytotoxicity; thus, subsequent experimental exposure was conducted at concentrations of 10-50 µM. The expression levels of CYP7A1 and TG synthesis-related genes and levels of TG and total BA were observed to increase in HepG2 cells. Molecular docking analysis revealed direct interactions between PTC or PTC-d and CYP7A1 protein. To further investigate the underlying mechanisms, PTC and PTC-d were treated to HepG2 cells in which CYP7A1 expression was knocked down using siCYP7A1. It was observed that PTC and PTC-d affected the BA metabolism process and regulated the glycolipid metabolism process by promoting the expression of CYP7A1. In summary, we comprehensively analyzed the effects and mechanisms of PTC and PTC-d on cellular metabolism in HepG2 cells, providing theoretical data for evaluating the safety and potential risks associated with these substances.
Subject(s)
Triazoles , Humans , Up-Regulation , Hep G2 Cells , Molecular Docking Simulation , Triazoles/toxicity , Triazoles/chemistryABSTRACT
Microplastics (MPs) can absorb environmental pollutants from the aquatic environment to cause mixed toxicity, which has received widespread attention. However, studies on the joint effects of MPs and insecticides are limited. As one of the most widely used pyrethroids, there was a large amount of residual cypermethrin (CYP) in water due to insufficient decomposition. Here, adult female zebrafish were exposed to MPs, CYP, and their mixtures for 21 days, respectively. After exposures, the MPs and CYP caused tissue damage to the liver. Hepatic triglyceride (TG) level increased significantly after MPs + CYP exposure, and the expression of genes about glycolipids metabolism was significantly altered. Furthermore, metabolome results suggested that MPs + CYP exposure resulted in increased content of some glycerophospholipid, affecting phospholipid metabolism-related pathways. In addition, through 16 s rDNA sequencing, it was found that MPs + CYP led to significant changes in the proportion of dominant phyla. Interestingly, Cetobacterium which increased in CYP and the co-exposure group was positively correlated with most lipid metabolites. Our results suggested that co-exposure to MPs and CYP enhanced the disturbances in hepatic phospholipid metabolism by affecting the gut microbial composition, while these changes were not observed in separate treatment groups. These results emphasized the importance of studying the joint toxicity of MPs and insecticides.
Subject(s)
Gastrointestinal Microbiome , Insecticides , Perciformes , Pyrethrins , Water Pollutants, Chemical , Animals , Female , Polystyrenes/toxicity , Microplastics/toxicity , Zebrafish/metabolism , Plastics/toxicity , Insecticides/metabolism , Phospholipids/metabolism , Pyrethrins/metabolism , Liver/metabolism , Perciformes/metabolism , Water Pollutants, Chemical/toxicityABSTRACT
Sodium hypochlorite (NaClO) and cadmium (Cd) are widely co-occurring in natural aquatic environment; however, no study has been conducted on effects of their combined exposure on aquatic organisms. To assess effects of exposure to NaClO and Cd in zebrafish larvae, we designed six treatment groups, as follows: control group, NaClO group (300 µg/L), 1/100 Cd group (48 µg/L), 1/30 Cd group (160 µg/L), NaClO+1/100 Cd group, and NaClO+1/30 Cd group analyzed behavior, neurological function and cardiac function. Results revealed that exposure to 1/30 Cd and NaClO+1/30 Cd caused abnormal embryonic development in larvae by altering body morphology and physiological indicators. Combined exposure to NaClO and 1/30 Cd affected the free-swimming activity and behavior of larvae in response to light-dark transition stimuli. Moreover, exposure to 1/30 Cd or NaClO+1/30 Cd resulted in a significant increase in tyrosine hydroxylase and acetylcholinesterase activities, as well as significant changes of various neurotransmitters. Lastly, exposure to 1/30 Cd or NaClO+1/30 Cd influenced the transcription of cardiac myosin-related genes and disturbed the myocardial contractile function. Altogether, our results suggested that combined exposure to NaClO and Cd induced oxidative damage in larvae, resulting in detrimental effects on nervous system and cardiac function, thus altering their swimming behavior.
Subject(s)
Water Pollutants, Chemical , Zebrafish , Animals , Zebrafish/physiology , Cadmium/toxicity , Sodium Hypochlorite/pharmacology , Larva , Acetylcholinesterase , Neurotransmitter Agents , Water Pollutants, Chemical/toxicityABSTRACT
Ochratoxin A (OTA) is a mycotoxin, and triadimefon (TDF) is a triazole fungicide. These compounds are prevalent in the environment, and their residues have been detected in crops. However, the precise health risks associated with mycotoxins and fungicides are not fully elucidated. In this work, five-week-old mice were gavage with OTA (0.3 and 1.5 mg/kg/day), TDF (10 and 50 mg/kg/day), and OTA + TDF (0.3 + 10 and 1.5 + 50 mg/kg/day) for 28 days. Exposure to OTA, TDF, and OTA + TDF led to significant alterations in liver total cholesterol (TC), triglyceride (TG), and glucose (GLU) levels, as well as in genes associated with glycolipid metabolism in mice. Reduced acylcarnitine levels in serum indicated that OTA, TDF, and co-exposure inhibited fatty acid (FA) ß-oxidation. Furthermore, OTA and TDF disrupted the integrality of the gut barrier function and altered the structure of the intestinal microbiota. These findings suggested that OTA, TDF, and their co-exposure might disrupt the intestinal barrier, alter the structure of the microbiota, and subsequently inhibit FA ß-oxidation, indicating the interference of OTA and TDF with glycolipid-related intestinal barrier dysfunction. Moreover, our data revealed a toxic additive effect between OTA and TDF, providing a foundation for assessing the combined toxicity risk of mycotoxins and fungicides.
Subject(s)
Fungicides, Industrial , Mycotoxins , Ochratoxins , Animals , Mice , Fungicides, Industrial/toxicity , Triazoles/toxicity , GlycolipidsABSTRACT
Antibiotic residues and antibiotic resistance genes (ARGs) in fruits and vegetables pose public health risks via the food chain, attracting increased attention. Antibiotics such as streptomycin, used directly on seedless grapes or introduced into vineyard soil through organic fertilizers. However, extensive data supporting the risk assessment of antibiotic residues and resistance in these produce remains lacking. Utilizing metagenomic sequencing, we characterized Shine Muscat grape antibiotic resistome and mobile genetic elements (MGEs). Abundant MGEs and ARGs were found in grapes, with 174 ARGs on the grape surface and 32 in the fruit. Furthermore, our data indicated that soil is not the primary source of these MGEs and ARGs. Escherichia was identified as an essential carrier and potential transmitter of ARGs. In our previous study, streptomycin residue was identified in grapes. Further short-term exposure experiments in mice revealed no severe physiological or histological damage at several environment-related concentrations. However, with increased exposure, some ARGs levels in mouse gut microbes increased, indicating a potential threat to animal health. Overall, this study provides comprehensive insights into the resistance genome and potential hosts in grapes, supporting the risk assessment of antibiotic resistance in fruits and vegetables.
Subject(s)
Anti-Bacterial Agents , Vitis , Animals , Mice , Anti-Bacterial Agents/pharmacology , Genes, Bacterial , Streptomycin , Drug Resistance, Microbial/genetics , Soil/chemistry , Risk AssessmentABSTRACT
Carbendazim (CBZ) and prochloraz (PCZ) are broad-spectrum fungicides used in agricultural peat control. Both fungicides leave large amounts of residues in fruits and are toxic to non-target organisms. However, the combined toxicity of the fungicides to non-target organisms is still unknown. Therefore, we characterized the toxic effects of dietary supplementation with CBZ, PCZ, and their combination for 90 days in 6-week-old male Institute of Cancer Research (ICR) mice. CBZ-H (100 mg/kg day), PCZ-H (10 mg/kg day), and their combination treatments increased the relative liver weights and caused liver injury. The serum total cholesterol (TC), triglyceride (TG), glucose (Glu), pyruvate (PYR), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were reduced, and synergistic toxicity was observed. Hepatic transcriptome revealed that 326 differentially expressed genes (DEGs) of liver were observed in the CBZ treatment group, 149 DEGs in the PCZ treatment group, and 272 DEGs in the combination treatment group. According to KEGG enrichment analysis, the fungicides and their combination affected lipid metabolism, amino acid metabolism, and ferroptosis. In addition, the relative mRNA levels of key genes involved in lipid metabolism were also examined. Compared with individual exposure, combined exposure to CBZ and PCZ caused a more obvious decrease in the expression of some genes related to glycolipid metabolism. Furthermore, the relative mRNA levels of some key genes in the combination treatment group were lower than those in the CBZ and PCZ treated groups. In summary, CBZ, PCZ, and their combination generally caused hepatotoxicity and glycolipid metabolism disorders, which could provide new insights for investigating the combined toxicity of multiple fungicides to animals.
Subject(s)
Benzimidazoles , Carbamates , Fungicides, Industrial , Imidazoles , Mice , Male , Animals , Fungicides, Industrial/pharmacology , Liver , Gene Expression Profiling , Cholesterol, LDL/metabolism , Glycolipids/metabolism , RNA, Messenger/metabolismABSTRACT
BACKGROUND: The dissemination of antibiotic resistance genes (ARGs) poses a substantial threat to environmental safety and human health. Herein, we present a longitudinal paired study across the swine lifetime from birth to market, coupled with metagenomic sequencing to explore the dynamics of ARGs and their health risk in the swine fecal microbiome. RESULTS: We systematically characterized the composition and distribution of ARGs among the different growth stages. In total, 829 ARG subtypes belonging to 21 different ARG types were detected, in which tetracycline, aminoglycoside, and MLS were the most abundant types. Indeed, 134 core ARG subtypes were shared in all stages and displayed a growth stage-associated pattern. Furthermore, the correlation between ARGs, gut microbiota and mobile genetic elements (MGEs) revealed Escherichia coli represented the main carrier of ARGs. We also found that in most cases, the dominant ARGs could be transmitted to progeny piglets, suggesting the potential ARGs generation transmission. Finally, the evaluation of the antibiotic resistance threats provides us some early warning of those high health risk ARGs. CONCLUSIONS: Collectively, this relatively more comprehensive study provides a primary overview of ARG profile in swine microbiome across the lifetime and highlights the health risk and the intergenerational spread of ARGs in pig farm.