Multi-omics profiling and biochemical assays reveal the acute toxicity of environmental related concentrations of Di-(2-ethylhexyl) phthalate (DEHP) on the gill of crucian carp (Carassius auratus)

Liu, Yingjie; Chen, Zhongxiang; Li, Shanwei; Ding, Lu; Wei, Xiaofeng; Han, Shicheng; Wang, Peng; Sun, Yanchun

doi:10.1016/j.chemosphere.2022.135814

Cited by 23 publications

(7 citation statements)

References 65 publications

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“…Thus, alterations in purine metabolism may be due to physiological requirements for DNA repair and RNA synthesis. In addition, increased purine metabolic activity causes ROS overproduction and oxidative stress, which could further explain the occurrence of oxidative damage …”

Section: Resultsmentioning

confidence: 99%

Environmentally Relevant Concentrations of Propofol-Induced Metabolic Dysfunction in Zebrafish: Mechanistic Insights into Integrated Hepatic Transcriptomic and Metabolomic Analyses

Jiang,

Li,

Zhang

et al. 2024

ACS EST Water

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Propofol is increasingly perceived as an emerging threat to aquatic ecosystems, although the ecotoxicity and underlying mechanisms of propofol on aquatic life have not yet been clearly established. In this study, zebrafish (Danio rerio) was exposed to different concentrations of propofol (0.008, 0.04, and 0.2 mg•L −1 ) to probe the effect of propofol on functional metabolism and the ecological response mechanism in aquatic organisms. Propofol induced severe hepatic damage, including increased interstitial spaces and nuclear malformations at the tissue level. Reactive oxygen species (ROS) production and lipid peroxidation in zebrafish were induced after 28 days of exposure, while the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were substantially increased, suggesting that propofol may influence hepatic tissue injury through exacerbating oxidative damage. Exacerbated levels of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) were indicative of dysregulated lipid metabolism. Comprehensive transcriptomics and metabolomics analyses showed that propofol mainly changed the glycerophospholipid metabolism, citric acid cycle, and purine metabolism, and the disorders of these pathways can aggravate lipid accumulation and oxidative damage. Overall, this study revealed the mechanisms of hepatotoxicity and metabolic dysfunction of propofol on zebrafish, providing constructive insights for a comprehensive assessment of the toxicity risk posed by propofol to aquatic environmental health.

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Section: Resultsmentioning

confidence: 99%

Environmentally Relevant Concentrations of Propofol-Induced Metabolic Dysfunction in Zebrafish: Mechanistic Insights into Integrated Hepatic Transcriptomic and Metabolomic Analyses

Jiang,

Li,

Zhang

et al. 2024

ACS EST Water

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“…40−44 Fish exposure studies have showed that DEHP interferes with the metabolism of lipids, with the most-affected metabolites including PLs (PCs and PEs), LPLs (LPEs and lysophosphatidates), GLs (DGs and triacylglycerols), sphingolipids (Sphs; sphingosines and sphingomyelins), and FAs. 41,45 Similarly, in liver tissues of mice or rats exposed to DEHP, the most-affected pathways have been found to be those involved in the metabolism of lipids such as PLs, LPLs, GLs, Sphs, cholesterol esters (CEs), and FAs. 42,46 Thus, PLs, LPLs, GLs, Sphs, CEs, and FAs are the lipid metabolites that are primarily affected by exposure to DEHP via a peroxisome proliferator-activated receptormediated pathway.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…DEHP, being a metabolic disruptor, can disrupt the metabolic homeostasis of lipid molecules typically by activation of the nuclear peroxisome proliferator-activated receptors, leading to a series of adverse effects on health (e.g., nonalcoholic fatty liver disease). − Fish exposure studies have showed that DEHP interferes with the metabolism of lipids, with the most-affected metabolites including PLs (PCs and PEs), LPLs (LPEs and lysophosphatidates), GLs (DGs and triacylglycerols), sphingolipids (Sphs; sphingosines and sphingomyelins), and FAs. , Similarly, in liver tissues of mice or rats exposed to DEHP, the most-affected pathways have been found to be those involved in the metabolism of lipids such as PLs, LPLs, GLs, Sphs, cholesterol esters (CEs), and FAs. , Thus, PLs, LPLs, GLs, Sphs, CEs, and FAs are the lipid metabolites that are primarily affected by exposure to DEHP via a peroxisome proliferator-activated receptor-mediated pathway. In the current study, H–D exchange experiments revealed that DEHP competes with D-labeled lipids for binding to the pocket of enzymes involved in lipid biotransformation, and in vitro and in vivo exposure experiments showed that this process may affect the concentrations of endogenous PLs, LPLs, CLs, and MLCLs (as shown in Figure a) through interference with the catabolism or anabolism of these endogenous metabolites.…”

Section: Resultsmentioning

confidence: 99%

Enzyme-Catalyzed Hydrogen–Deuterium Exchange between Environmental Pollutants and Enzyme-Regulated Endogenous Metabolites

Liu

Cui

Huang

et al. 2023

Environ. Sci. Technol.

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Environmental pollutants can disrupt the homeostasis of endogenous metabolites in organisms, leading to metabolic disorders and syndromes. However, it remains highly challenging to efficiently screen for critical biological molecules affected by environmental pollutants. Herein, we found that enzyme could catalyze hydrogen−deuterium (H−D) exchange between a deuterium-labeled environmental pollutant [D 38 -bis(2ethylhexyl) phthalate (D 38 -DEHP)] and several groups of enzymeregulated metabolites [cardiolipins (CLs), monolysocardiolipins (MLCLs), phospholipids (PLs), and lysophospholipids (LPLs)]. A high-throughput scanning identified the D-labeled endogenous metabolites in a simple enzyme [phospholipase A 2 (PLA 2 )], enzyme mixtures (liver microsomes), and living organisms (zebrafish embryos) exposed to D 38 -DEHP. Mass fragmentation and structural analyses showed that similar positions were D-labeled in the CLs, MLCLs, PLs, and LPLs, and this labeling was not attributable to natural metabolic transformations of D 38 -DEHP or incorporation of its D-labeled side chains. Molecular docking and competitive binding analyses revealed that DEHP competed with D-labeled lipids for binding to the active site of PLA 2 , and this process mediated H−D exchange. Moreover, competitive binding of DEHP against biotransformation enzymes could interfere with catabolic or anabolic lipid metabolism and thereby affect the concentrations of endogenous metabolites. Our findings provide a tool for discovering more molecular targets that complement the known toxic endpoints of metabolic disruptors.

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“…17 With the continuous development of molecular biotechnology, omics research can effectively uncover the underlying molecular mechanism of action and the targets of environmental toxicants in the aquatic animal model. 18,19 The integrated omics analysis has been adopted by researchers to elucidate the unique pathways and multifaceted mechanisms. For example, combined transcriptomics and metabolomics clarified the toxic effects in grass carp under anesthetic stress.…”

Section: Introductionmentioning

confidence: 99%

Effect of chronic deltamethrin exposure on brain transcriptome and metabolome of juvenile crucian carp

Wu,

Gao,

Xie

et al. 2023

Environmental Toxicology

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Deltamethrin (Del), a widely administered pyrethroid insecticide, has been established as a common contaminant of the freshwater environment and detected in many freshwater ecosystems. In this study, we investigated the changes in brain transcriptome and metabolome of crucian carp after exposure to 0.6 μg/L Del for 28 days. Elevated MDA levels and inhibition of SOD activity indicate damage to the antioxidant system. Moreover, a total of 70 differential metabolites (DMs) were identified using the liquid chromatography‐mass spectrometry, including 32 upregulated and 38 downregulated DMs in the Del‐exposed group. The DMs associated with chronic Del exposure were enriched in steroid hormone biosynthesis, fatty acid metabolism, and glycerophospholipid metabolism for prostaglandin G2, 5‐oxoeicosatetraenoic acid, progesterone, androsterone, etiocholanolone, and hydrocortisone. Transcriptomics analysis revealed that chronic Del exposure caused lipid metabolism disorder, endocrine disruption, and proinflammatory immune response by upregulating the pla2g4, cox2, log5, ptgis, lcn, and cbr expression. Importantly, the integrative analysis of transcriptomics and metabolomics indicated that the arachidonic acid metabolism pathway and steroid hormone biosynthesis were decisive processes in the brain tissue of crucian carp after Del exposure. Furthermore, Del exposure perturbed the tight junction, HIF‐1 signaling pathway, and thyroid hormone signaling pathway. Overall, transcriptome and metabolome data of our study offer a new insight to assess the risk of chronic Del exposure in fish brains.

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Multi-omics profiling and biochemical assays reveal the acute toxicity of environmental related concentrations of Di-(2-ethylhexyl) phthalate (DEHP) on the gill of crucian carp (Carassius auratus)

Cited by 23 publications

References 65 publications

Environmentally Relevant Concentrations of Propofol-Induced Metabolic Dysfunction in Zebrafish: Mechanistic Insights into Integrated Hepatic Transcriptomic and Metabolomic Analyses

Environmentally Relevant Concentrations of Propofol-Induced Metabolic Dysfunction in Zebrafish: Mechanistic Insights into Integrated Hepatic Transcriptomic and Metabolomic Analyses

Enzyme-Catalyzed Hydrogen–Deuterium Exchange between Environmental Pollutants and Enzyme-Regulated Endogenous Metabolites

Effect of chronic deltamethrin exposure on brain transcriptome and metabolome of juvenile crucian carp

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