ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Xiuyan He,Wenji Hu,Yao Zu
The widespread presence of antihistamines such as loratadine in aquatic environments poses emerging ecotoxicological concerns, yet their developmental impacts remain poorly characterized. In this study, zebrafish embryos were exposed to loratadine (35–350 μg/L) to evaluate its developmental effects. By 2–3 days post-fertilization (dpf), exposed larvae exhibited marked cardiac defects, including pericardial edema, reduced heart rate and cardiac output, and fractional area change ( p < 0.05). By 4–6 dpf, a complete failure of swim bladder inflation was observed in the exposed group, confirmed by histological analysis showing significantly reduced bladder area ( p < 0.0001). Behavioral assays revealed impaired locomotion, with decreased total distance and swimming speed ( p < 0.001). Molecular analyses showed that loratadine significantly altered the expression of cardiac genes ( acta1b , atp2a2a , gata4 , hand2 , tbx5a ) and suppressed key regulators of swim bladder development ( fgf10a , smo , gli2a , fzd2 , fzd5 , wnt2bb ) ( p < 0.05), ultimately resulting in abnormal cardiac and swim bladder development. These findings highlight the pronounced ecotoxicological impact of loratadine on aquatic vertebrates and reinforce the urgent need for improved environmental surveillance and wastewater remediation strategies to curb pharmaceutical contamination in freshwater ecosystems.
研究领域:
发育生物学
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生态毒理学
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药理学
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环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
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2019
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IF 5.108
Yan Ma,Luxiu Zang,Danting Wang,Jiahui Jiang,Caihong Wang,Xuedong Wang,Fang Fang,Huili Wang
Triclosan (TCS), one of the important bactericides , is widely used in personal care products, and its chronic exposure leads to severe toxic effects on the growth and development of blood vessels in zebrafish ( Danio rerio ). Herein, we screened out three differentially expressed miRNAs (miR-181a-5p, miR-132-3p and miR-128-3p) by sequencing and qRT-PCR analyses of 4–96-hpf TCS-exposed zebrafish, among which miR-181a-5p was found to regulate many signaling pathways involved in fatty acid biosynthesis and phosphatidylimositol signaling systems. By O-dianisidine staining, TCS-exposure resulted in decreased distribution of red blood cells and induced blood hypercoagulable state and thrombotic effects. Defective subintestinal veins (SIVs), and decreased branching and curvature of blood vessels were observed with increasing TCS-exposure concentrations. After microinjection of miR-181a-5p mimic and inhibitor, zebrafish malformation type and percentage were prominently increased such as distorted SIV vessels along with reduced venation and abnormal branches by ALP staining. Overexpressed miR-181a-5p had a greater effect on development and branching patterns of arteries and veins than its knockdown. By laser confocal microscopy observation, the 72-hpf Tg (flk1: mCherry) zebrafish obviously displayed vascular proliferation and ablation in the miR-181a-5p mimic group. Microinjection of miR-181a-5p mimics and inhibitors led to abnormal expressions (20–50%) of two key target genes ( pax2a and vash2 ) by WISH, and increased malformation percentages (18–45%) by IOD analysis. Overexpression of vash2 led to the inhibitory or promoting effects on the expression of PI3K signaling pathway-related genes, proving that the effect of vash2 on development of blood vessels could be realized by inhibiting PI3K signaling pathway. These observations lay theoretical foundation for deep insight into the molecular mechanisms on TCS-induced cardiovascular diseases.
研究领域:
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
ENVIRONMENTAL POLLUTION
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2025
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IF 7.3
Yiyun Liu,Yan-Ling Liao,Jin-Xia Wang,Bao-Fu Zhang,Qi-Ping Tang,Yuan Ding,Si-Jia Zuo,Qin-Hong Zhou,De-Sheng Pei
The widespread application of nano-cerium dioxide (Nano-CeO 2 ) in agriculture, industry, and other fields has led to an increasing amount of it being released into the environment and becoming a pollutant with potential biological hazards. However, studies on the effects of ceria on cardiovascular development were limited. This study aims to detect the cardiovascular toxicity of Nano-CeO 2 , focusing on its impact on zebrafish hematopoietic function and cardiac development, and to explore its potential molecular mechanisms. We found that exposing zebrafish embryos to different concentrations of Nano-CeO 2 after 6 hpf of fertilization does not hinder the growth and development of zebrafish embryos during their early life stages. However, RNA-Seq analysis indicates that the hematopoietic system of zebrafish is suppressed, the ECM-receptor interaction pathway is disrupted, and the expression of related genes is significantly downregulated. The results of o-dianisidine staining, neutral red staining, and Sudan black staining showed that the hemoglobin, macrophages, and neutrophils of zebrafish were reduced, and the vascular dysplasia of zebrafish was observed. Meanwhile, Reactive oxygen species (ROS) accumulated in the heart of zebrafish larvae treated with Nano-CeO 2 , and heart development-related genes ( nppa , hand2 , nppb , nkx2.5 , and myh7 ) were significantly down-regulated, while gata4 was up-regulated. The addition of the integrin agonist manganese ions restored the expression of genes related to ECM-receptor interaction pathways, alleviating cardiovascular abnormalities caused by Nano-CeO 2 . Besides, significant changes in cardiac histopathology were observed with long-term exposure (120 d post-fertilization), indicating that Nano-CeO 2 exposure affected the development of the cardiovascular system in zebrafish. In summary, acute and chronic exposure to Nano-CeO 2 exhibits cardiovascular toxicity in zebrafish, affecting hematopoietic function and cardiac development, and the mechanism may be related to the ECM-receptor interaction pathway. This study provides useful information for a comprehensive understanding of the toxicity mechanisms and environmental risks of Nano-CeO 2 .
研究领域:
环境毒理学
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分子生物学
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发育生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL RESEARCH
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2024
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IF 7.7
Jianjun Chen,Yinyin Wei,Jiameng Zhou,Xianglin Cao,Rongjie Yuan,Yaoyajie Lu,Yi Guo,Xue Shao,Weidi Sun,Mengtao Jia,Xiuli Chen
Tributyltin (TBT) can be used as an antifouling agent with anticorrosive, antiseptic and antifungal properties and is widely used in wood preservation and ship painting. However, it has recently been found that TBT can be harmful to aquatic organisms. In this study, to gain insight into the effects of TBT with respect to the development of the cardiovascular system in zebrafish embryos, zebrafish embryos were exposed to different concentrations of TBT solutions (0.2 μg/L, 1 μg/L, and 2 μg/L) at 2 h post-fertilization (hpf) TBT exposure resulted in decreased hatchability and heart rate, deformed features such as pericardial edema, yolk sac edema, and spinal curvature in zebrafish embryos, and impaired heart development. Expression of cardiac development-related genes ( vmhc , myh6 , nkx2.5 , tbx5a , gata4 , tbx2b , nppa ) is dysregulated. Transgenic zebrafish Tg ( fli1 : EGFP) were used to explore the effects of TBT exposure on vascular development. It was found that TBT exposure could lead to impaired development of intersegmental vessels (ISVs), common cardinal vein (CCV), subintestinal vessels (SIVs) and cerebrovascular. The expression of vascular endothelial growth factor (VEGF) signaling pathway-related genes ( flt1 , flt4 , kdr , vegfa ) was downregulated. Biochemical indices showed that ROS and MDA levels were significantly elevated and that SOD and CAT activities were significantly reduced. The expression of key genes for prostacyclin synthesis ( pla2 , ptgs2a , ptgs2b , ptgis , ptgs1 ) is abnormal. Therefore, it is possible that oxidative stress induced by TBT exposure leads to the blockage of arachidonic acid (AA) production in zebrafish embryos, which affects prostacyclin synthesis and consequently the normal development of the heart and blood vessels in zebrafish embryos.
研究领域:
环境毒理学
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发育生物学
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水生毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2025
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IF 8
Chuan Liang,Yang Chen,Yunzhe Ling,Peirun Li,Jiahao Liu,Xuantian Li,Yanhua Xu,Zhiying Liu
Non-steroidal anti-inflammatory drugs (NSAIDs), though designed to target specific molecular pathways, pose significant environmental risks to non-target organisms, particularly marine fish. This study investigated the toxicity mechanisms and adaptive responses to diclofenac (DCF) and meloxicam (MEX) during the early life stages (ELS) of Oryzias melastigma at environmentally relevant concentrations over a 31-day period. Mechanistic investigations of sub-lethal effects were conducted using Enzyme-Linked Immunosorbent Assay (ELISA), RNA sequencing (RNA-Seq) and quantitative PCR (qPCR). The results revealed that cyclooxygenase (COX) inhibition disrupted the renin-angiotensin system, leading to an accumulation of angiotensin II and cardiovascular developmental defects. Additionally, downregulation of the pla2 gene reduced substrates essential for COX enzyme activity, exacerbating the effects. Although NSAIDs are known to affect the digestive system, no significant effects on developmental factors were observed. RNA-Seq and qPCR analyses revealed an adaptive upregulation of key genes, including ace2 and cyp7a1 , involved in cardiovascular and metabolic regulation. Furthermore, 16S rRNA sequencing identified shifts in the microbial community, particularly in g_Rubritalea and g_Sphingomonas genera. Both the upregulated genes and the altered microbial taxa likely played a role in mitigating toxic effects and promoting homeostasis. Moreover, molecular docking suggested that MEX exhibited stronger sub-lethal effects than DCF, likely due to its higher binding affinity to COX. These findings provide valuable insights into NSAID toxicity mechanisms in marine fish, highlighting the importance of adaptive responses in countering environmental stress and underscoring the long-term ecological risks of chronic NSAID exposure.
研究领域:
海洋毒理学
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环境科学
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药理学
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分子生物学
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发育生物学
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生态毒理学
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微生物学
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生物信息学
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药物发现
✓ 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）