SCIENCE OF THE TOTAL ENVIRONMENT
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2023
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IF 9.8
Qian Liu,Cheng Xu,Jing Jin,Wenxiang Li,Jingjia Liang,Shijie Zhou,Zhenkun Weng,Yong Zhou,Xudong Liao,Aihua Gu
Lead (Pb) is widely used in industrial and daily-use consumer products. Early-life exposure may increase the risk of lead-related heart problems in childhood. However, the effects of early-life lead exposure on fetal heart development and long-term cardiac outcomes are unknown. In this study, pregnant ICR mice were exposed to lead acetate trihydrate (50 mg/kg/d) via oral gavage from gestation day 1.5 until offspring weaning. Thereafter, the second hit model was established, two groups of offspring (4 weeks old) were either administered sterile saline or Angiotensin II (Ang II) for 4 weeks until euthanasia. We investigated lead-induced offspring heart damage from embryonic period to adulthood by echocardiographic analysis, pathological H&E staining, and ultrastructural examination, as well as mitochondrial function detection. The results showed early-life lead exposure predisposed offspring mice to decreased ejection fraction, increased left ventricular volume, accompanied by hypertrophy and dilation, cardiomyocyte sarcomere dysplasia, abnormal mitochondrial structure, mitochondrial dysfunction, and decreased expression of key sarcomeric and mitochondrial genes, rendering them more susceptible to cardiac hypertrophy, vascular wall thickening, cardiac fibrosis, apoptosis, and heart failure induced by Ang II infusion. This study elucidates early-life low dose lead exposure compromises cardiac development and exacerbates second hit-induced cardiac pathological responses in adulthood, which furnishes crucial scientific evidence pertaining to the cardiac toxicity and risk evaluation associated with early-life exposure to lead.
研究领域:
毒理学
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心血管医学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Yuanzhao Wu,Ye'anlun Zhu,An Cheng,Weixuan Yao,Binjie Wang,Ruonan Zheng,Jiye Wang
Tefluthrin, a pyrethroid insecticide commonly used in soil, has raised concerns due to its widespread use and residual presence in aquatic environments. Nevertheless, studies on the toxicological mechanisms of tefluthrin at relevant concentrations during the early life stages of aquatic species remain limited. In this study, we assessed the developmental effects of tefluthrin exposure at concentrations of 1, 10, and 100 μg/L over 8 days on zebrafish embryos/larvae. Exposure to 100 μg/L of tefluthrin significantly reduced hatchability and survival rates, leading to cardiac edema and skeletal deformities. Alizarin Red and Alcian Blue staining showed reduced skeletal mineralization and disrupted craniofacial morphology. Importantly, tefluthrin exposure resulted in the dysregulation of important genes involved in heart and skeletal development, including nppa , vmhc , sox9b , gata4 , runx2a , shha , sp7 , and bmp2b . Mechanistically, tefluthrin exposure increased reactive oxygen species (ROS), decreased antioxidant enzyme activities (SOD, CAT), and elevated malondialdehyde (MDA). Furthermore, exposure to tefluthrin caused significant cell apoptosis in larvae, accompanied by dysregulation in the transcriptional expression of apoptotic genes ( bcl2 , bax , p53 , and caspase-3 ). Treatment with the antioxidant astaxanthin alleviated tefluthrin-induced oxidative stress and provided protection against heart and skeletal toxicity. In conclusion, this study demonstrated that tefluthrin's developmental toxicity affected heart and skeletal development, with mechanisms involving changes in gene expression, oxidative stress, and apoptosis, providing valuable insights for assessing environmental and food contamination risks.
研究领域:
毒理学
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环境科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
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2025
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IF 5.1
Wenwen Zha,Ziang Wang,Weitao Hu,Chenkai Ge,Wenbin Yuan,Qinyuan Shen,Weirong Li,Wanqing Chen,Jingrong Tang,Zhonghao Xiao,Yunlong Meng,Lirong Huang,Zilin Zhong,Tao-Sheng Li,Jianjun Chen,Zigang Cao
Bexarotene (Bex) is a selective retinoid X receptor (RXR) agonist and is commonly used as an anti-tumor drug in the clinic to treat patients with cutaneous T-cell lymphoma (CTCL). With the widespread use of this drug, people are increasingly concerned about its side effects and safety of use. At present, the effects of bexarotene drugs on the health of organisms remain uncertain, but retinoid drugs are generally biologically active and may pose potential risks to them. Therefore, in this study, we used a zebrafish model to evaluate the effects of Bex on embryonic development. Six hours after fertilization, we exposed zebrafish embryos to 3 μg/L, 6 μg/L, and 9 μg/L bexarotene. At 96 hpf, compared with the control group, zebrafish embryos exposed to bexarotene showed obvious heart and liver development defects, including reduced hatching rate, pericardial enlargement, heart rate disorder, yolk sac edema, small liver area and abnormal photo-optical motor responses. Transcriptome and qPCR results showed abnormal expression of genes related to heart and liver development was induced by Bexarotene. Mechanistically, bexarotene induced a significant upregulation of the transcriptional expression levels of genes related to the Wnt signaling pathway, and IWR-1 was able to effectively rescue the heart and liver developmental defects of zebrafish caused by bexarotene. Therefore, our study showed that bexarotene may cause zebrafish embryonic developmental defects by upregulating the Wnt signaling pathway, revealing the side effects and associated novel mechanisms of bexarotene, and providing a theoretical basis for its safe and effective use in the treatment of clinically related diseases.
研究领域:
发育生物学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2025
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IF 4.3
Xinhao Ye,Mijia Li,YunLong Meng,Shiyi Duan,Sijie Zhang,Keyuan Zhong
Cardiac looping is a crucial process during embryonic development. Abnormalities or failures in cardiac looping can lead to congenital heart defects, thereby affecting normal physiological function. Environmental pollutant exposure is one of the major causes of cardiac looping failure. D-tetramethrin is a hygienic insecticide widely used in households and public places, that can enter the human body through contact, insect transmission, and the food chain, thereby impacting human health. In this study, zebrafish embryos were exposed to different concentrations of D-tetramethrin to analyze its effects on heart development, and oxidative stress levels within the embryos. Additionally, qPCR was employed to analyze the transcription and the expression levels of genes related to heart development and function. The results showed that (1) D-tetramethrin exposure significantly reduced heart rate and increased the distance between the sinus venosus and the bulbus arteriosus (SV-BA), which suggested that D-tetramethrin induced cardiac looping failure and led to abnormal heart function. (2) D-tetramethrin exposure elevated the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in zebrafish embryos while decreasing the enzyme activities of key antioxidant stress enzymes, such as catalase (CAT) and superoxide dismutase (SOD). (3) D-tetramethrin exposure resulted in a significant downregulation of the transcription of cardiac looping-related genes ( Myh6 , Nkx2.5 , Tbx2b , Tbx5a, Tnnt2c and Hand2 ) and heart function-related genes ( Gata4, Vmhc and Nppa ). Our findings indicate that D-tetramethrin causes the accumulation of ROS, which in turn alters the transcription levels of genes related to cardiac looping, ultimately resulting in cardiac looping failure.
研究领域:
发育生物学
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毒理学
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环境科学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
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2023
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IF 8.8
Yuhua Zuo,Chao Chen,Fasheng Liu,Hongmei Hu,Chao Wen,Si Dong,Xinjun Liao,Zigang Cao,Xiaoyun Shi,Zilin Zhong,Jianjun Chen,Huiqiang Lu
Benzophenone (BP) is found in many popular consumer products, such as cosmetics. BP potential toxicity to humans and aquatic organisms has emerged as an increased concern. In current study, we utilized a zebrafish model to assess BP-induced developmental cardiotoxicity. Following BP exposure, zebrafish embryos exhibited developmental toxicity, including increased mortality, reduced hatchability, delayed yolk sac absorption, and shortened body length. Besides, BP exposure induced cardiac defects in zebrafish embryos, comprising pericardial edema, reduced myocardial contractility and rhythm disturbances, and altered expression levels of cardiac developmental marker genes. Mechanistically, BP exposure disturbed the redox state and increased the level of apoptosis in zebrafish cardiomyocytes. Transcriptional expression levels of Wnt signaling genes, involving lef1, axin2, and β-catenin , were upregulated after BP treatment. Inhibition of Wnt signaling with IWR-1 could rescue the BP-induced cardiotoxicity in zebrafish. In summary, BP exposure causes cardiotoxicity via upregulation of the Wnt signaling pathway in zebrafish embryos.
研究领域:
毒理学
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发育生物学
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环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2023
·
IF 9.8
Yang Yang,Yue Tao,Xiaodong Yi,Guanyu Zhong,Yanyan Gu,Yunhe Cui,Ying Zhang
Typical plasticizer di (2-ethylhexyl) phthalate (DEHP) has been demonstrated to induce cardiotoxicity in zebrafish, but the potential molecular mechanisms involved have not been fully elucidated. Aryl hydrocarbon receptor (AhR), an essential protein for inducing developmental abnormalities, has been demonstrated to be activated by DEHP in other species, but whether the AhR signaling pathway also contributes to DEHP-mediated cardiac developmental toxicity in zebrafish remains unclear. Firstly, molecular docking simulations initially confirmed the possibility that DEHP has AhR agonistic activity. To further confirm this conjecture, this work analyzed the changes of cardiac-related indexes in zebrafish stressed by DEHP at individual, protein, and gene levels. The results showed that DEHP mediated cardiac phenotypic developmental defects, increased CYP1A1 activity, and oxidative stress as well as significant changes in the expression levels of key proteins and genes of AhR, Wnt/β-catenin, and Nrf2-Keap1 signaling pathways. Notably, the addition of AhR inhibitors effectively alleviated the above negative effects, indicating that the AhR signaling pathway and its crosstalk with the Wnt/β-catenin signaling pathway is an essential pathway for DEHP-mediated cardiac developmental toxicity. Overall, this work enriches the molecular mechanism of DEHP-mediated cardiac developmental defects in zebrafish and provides a reliable biomarker for future environmental risk assessment of DEHP.
研究领域:
环境科学
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毒理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2024
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IF 8.2
Hao Sun,Zhazheng He,Yao Gao,Yanhan Yang,Yachang Wang,Aihua Gu,Jin Xu,Yingyi Quan,Yang Yang
The early stage of heart development is highly susceptible to various environmental factors. While the use of animal models has aided in identifying numerous environmental risk factors, the variability between species and the low throughput limit their translational potential. Recently, a type of self-assembling cardiac structures, known as human heart organoids (hHOs), exhibits a remarkable biological consistency with human heart. However, the feasibility of hHOs for assessing cardiac developmental risk factors remains unexplored. Here, we focused on the cardiac developmental effects of core components of Glyphosate-based herbicides (GBHs), the most widely used herbicides, to evaluate the reliability of hHOs for the prediction of possible cardiogenesis toxicity. GBHs have been proven toxic to cardiac development based on multiple animal models, with the mechanism remaining unknown. We found that polyoxyethylene tallow amine (POEA), the most common surfactant in GBHs formulations, played a dominant role in GBHs' heart developmental toxicity. Though there were a few differences in transcriptive features, hHOs exposed to sole POEA and combined POEA and Glyphosate would suffer from both disruption of heart contraction and disturbance of commitment in cardiomyocyte isoforms. By contrast, Glyphosate only caused mild epicardial hyperplasia. This study not only sheds light on the toxic mechanism of GBHs, but also serves as a methodological demonstration, showcasing its effectiveness in recognizing and evaluating environmental risk factors, and deciphering toxic mechanisms.
研究领域:
毒理学
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干细胞生物学
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心脏病学
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环境科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2022
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IF 14.224
Hongdan Wang,Yunqing Wang,Qiaoning Wang,Min Lv,Xizhen Zhao,Yunxia Ji,Xiaoyue Han,Xiaoyan Wang,Lingxin Chen
Microplastics (MPs) have the characteristics of large specific surface area, high hydrophobicity and surface charge, so they are easy to combine with other pollutants and cause toxic effects on aquatic organisms. Here, we prepared a polyvinyl chloride-microplastics (PVC-MPs) fragmentation model to simulate the real microplastic state, and characterized its composition, morphology, particle size and zeta potential . On this basis, we used single and compound exposure of PVC and di(2-ethylhexyl) phthalate (DEHP) to explore their effects on hatchability and mortality of zebrafish ( Danio rerio ) embryos and toxicity to oxidative stress and cardiac development in zebrafish larvae. Herein, PVC-MPs slowed down the hatching rate of zebrafish embryos and induced the death of zebrafish, while DEHP could slow down the induced of death, it had no effect on hatching rate. The PVC-MPs/DEHP single pollution could induce the reactive oxygen species (ROS) and activated the antioxidant defense signaling pathway, while the compound group showed the level of feedback autoregulation of NF-E2-related factor 2 (Nrf2) signaling pathway. The single pollution also could inhibit the expression of genes related to cardiac development, while the combined pollution showed an antagonistic effect. This study provided a theoretical basis for the ecotoxicology and biomonitoring of MPs in the natural state.
研究领域:
环境科学
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毒理学
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水生生物学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2024
·
IF 7.6
Yingying Liu,Xudong Jin,Yanan Ye,Zeqiong Xu,Zhongkun Du,Huachang Hong,Haiying Yu,Hongjun Lin,Xianfeng Huang,Hongjie Sun
3-bromine carbazole (3-BCZ) represents a group of emerging aromatic disinfection byproducts (DBP) detected in drinking water; however, limited information is available regarding its potential cardiotoxicity. To assess its impacts, zebrafish embryos were exposed to 0, 0.06, 0.14, 0.29, 0.58, 1.44 or 2.88 mg/L of 3-BCZ for 120 h post fertilization (hpf). Our results revealed that ≥1.44 mg/L 3-BCZ exposure induced a higher incidence of heart malformation and an elevated pericardial area in zebrafish larvae; it also decreased the number of cardiac muscle cells and thins the walls of the ventricle and atrium while increasing cardiac output and impeding cardiac looping. Furthermore, 3-BCZ exposure also exhibited significant effects on the transcriptional levels of genes related to both cardiac development ( nkx2.5 , vmhc , gata4 , tbx5 , tbx2b , bmp4 , bmp10 , and bmp2b ) and cardiac function ( cacna1ab , cacna1da , atp2a1l , atp1b2b , atp1a3b , and tnnc1a ). Notably, N-acetyl-L-cysteine, a reactive oxygen species scavenger, may alleviate the failure of cardiac looping induced by 3-BCZ but not the associated cardiac dysfunction or malformation; conversely, the aryl hydrocarbon receptor agonist CH131229 can completely eliminate the cardiotoxicity caused by 3-BCZ. This study provides new evidence for potential risks associated with ingesting 3-BCZ as well as revealing underlying mechanisms responsible for its cardiotoxic effects on zebrafish embryos.
研究领域:
环境科学
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毒理学
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发育生物学
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水生毒理学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
·
IF 6.1
Yang Zhang,Mingcong Chen,Krishna Baral,Cheng Chen,Yang Meng,Manling Zhang,Marady Hun,Hanyong Zhang,Mengchang Xu,Mingyi Zhao
With the extensive use of microplastics (MPs) and its plasticizer, more and more research focus on their combined effects on health risk. In this study, polystyrene (PS) and di(2-ethylhexyl) phthalate (DEHP) were selected as target contaminants, and zebrafish embryos were employed as a biological model to investigate the potential toxicity of co-exposure to microplastics and plastic additives on embryonic and cardiac development. These findings indicated that the simultaneous exposure to PS and DEHP markedly diminished the heart rate, survival rate, and impeded the hatching process. The combined exposure group exhibited elevated levels of oxidative stress and an increased number of apoptotic cells. Fluorescence photography of zebrafish embryos revealed an increase in the distance of SV-BA in combined exposure. Transcriptomics analysis revealed a reduction in the expression of yeats4 , a gene involved in regulating DNA damage response and cell death. Metabolomics analysis revealed that amino acid metabolism plays a critical role in the toxic effects of combined PS and DEHP exposure on zebrafish larvae, while the Apelin signaling pathway, vascular smooth muscle contraction, and calcium ion signaling pathway may be key pathways involved in the cardiac toxic effects of PS and DEHP co-exposure in zebrafish larvae.
研究领域:
环境毒理学
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发育生物学
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海洋污染研究
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生态毒理学
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转录组学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2022
·
IF 14.224
Guoliang Chen,Mingxing Wang,Panpan Zhu,Guixue Wang,Tingzhang Hu
As a newly-invented and highly-efficiency strobilurin fungicide , pyraoxystrobin (SYP-3343) has been recognized as a highly poisonous toxin for a variety of aquatic organisms. Nevertheless, the developmental toxicity and potential mechanism of SYP-3343 have not been well-documented. The results showed that SYP-3343 was relatively stable and maintained within the range of 20 % in 24 h, and the LC 50 value to embryos at 72 hpf was 17.13 μg/L. The zebrafish embryotoxicity induced by 1, 2, 4, and 8 μg/L SYP-3343 is demonstrated by repressive embryo incubation, enhancive mortality rate, abnormal heart rate, malformed morphological characteristic, and impaired spontaneous coiling, indicating SYP-3343 mostly exerted its toxicity in a dose- and time-dependent manner. Besides SYP-3343 was critically involved in regulating cell cycle, mitochondrial membrane potential, and reactive oxygen species production as well as zebrafish primary cells apoptosis, which can be mitigated using antioxidant N-acetyl- L -cysteine. A significant change occurred in total protein content, the biochemical indices, and antioxidant capacities owing to SYP-3343 exposure. Additionally, SYP-3343 altered the mRNA levels of heart development-, mitochondrial function-, and apoptosis-related genes in zebrafish embryos. These results indicated that SYP-3343 induced apoptosis accompanying reactive oxygen species-initiated mitochondrial dysfunction in zebrafish embryos.
研究领域:
毒理学
·
水生毒理学
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发育生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Sujing Wang,Na Zheng,Qirui An,Xiaoqian Li,Yining Ji,Yunyang Li,Changcheng Chen,Zhifei Xiu
The flame retardant tri (1, 3-dichloro-2-propyl) phosphate (TDCIPP) is widely present in environmental media and organisms. People have paid much attention to the growth and developmental toxicity of TDCIPP, but there is little information about its cardiotoxicity and potential mechanisms. In this study, marine medaka ( Oryzias melastigma ) embryos were exposed to TDCIPP solutions (0, 0.05, 0.5, 5, and 50 μg/L) for 21 days to investigate the adverse effects of TDCIPP on cardiac development. The results showed that TDCIPP exposure altered the heart rate at different stages of embryonic development. In addition, 50 μg/L TDCIPP resulted in increased sinus venosus (SV)–bulbus arteriosus (BA) distance, pericardial cysts, and cardiac linearization in newly hatched fish. During embryonic development, the expression level of key genes regulating cardiac development is disturbed. The early stage of cardiac development is the sensitive window period for the toxic effects of TDCIPP. Oxidative stress was observed in newly hatched juveniles, but no significant lipid peroxidation damage was observed. In addition, vitellogenin (VTG) levels in juvenile fish were significantly reduced. Our results show that TDCIPP exposure induces cardiotoxicity in marine medaka embryos, which is induced in the early stages and promotes heart defects by amplifying inflammatory responses at a later stage.
研究领域:
环境毒理学
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发育生物学
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心血管毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）