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Water · 2022 ·Vol. 14 ·期 23 ·3857 · IF 3.53

Toxic Effects and Mechanism of Pefloxacin on the Early Life Stage of Zebrafish (Danio rerio)

Rong Shen,Yichang Yu,Qinfang Liu,Ruili Wang,Rong Lan,Hui Feng,Ran Yu,Lihua Jin,Ye Li

Pefloxacin (PFLX) is a type of fluoroquinolone (FQ) that has been widely used in aquaculture and animal husbandry. It is also a new kind of pseudo-persistent pollutant, which has some toxic effects. In this study, zebrafish (Danio rerio) embryos were used as exposure models to analyze the toxicity of PFLX. The results showed that PFLX was absorbed on the outer membrane surface at the beginning, and then a few PFLX slowly entered the cytoplasm. The adsorption complied with the Langmuir isotherm adsorption model. The surface morphology of the embryonic membrane was changed. PFLX exposure had no effect on fetal autonomous movement, but it significantly inhibited the embryo hatching rate. After PFLX exposure, the embryo and larval survival rates showed a clear dose–effect relationship. Though PFLX exposure did not cause teratogenic toxicity, it still affected cardiovascular function. The potential toxicity mechanism and developmental toxicity of PFLX to zebrafish were revealed. These results could be important for studies concerning FQ toxicology.Keywords:pefloxacin;zebrafish;embryonic membrane;developmental toxicity

研究领域: 毒理学 · 环境科学
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MOLECULES · 2023 ·Vol. 28 ·期 17 ·6344 · IF 4.6

Epigallocatechin-3-Gallate Reduces Cd-Induced Developmental Toxicity of Bodysize in Caenorhabditis elegans via the PEK-1/eIF-2α/ATF-4 Pathway

Shuanghui Wang,Chuhong Chen,Yan Lu

Cadmium (Cd), a harmful heavy metal that has no biological purpose, can harm healthy fetal and child development. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in tea, has been shown to increase cell viability under Cd exposure and ameliorate Cd-induced kidney injury in adult male rats. Using theCaenorhabditis elegans(C. elegans) model, we demonstrated that EGCG mitigated Cd-induced body size developmental toxicity through a mechanism that did not involve chelation with EGCG and was not associated with Cd accumulation and efflux. Our research indicated that the beneficial effects of EGCG on Cd-induced body size developmental toxicity were associated with the mitigation of endoplasmic reticulum stress. Furthermore, our observations indicate that EGCG reduced Cd-induced developmental toxicity inC. elegansvia the PEK-1/eIF-2α/ATF-4 pathway. Our results provide important evidence for the potential benefits of consuming tea as a detoxification agent.Keywords:tea;EGCG;cadmium;Caenorhabditis elegans;developmental toxicity;endoplasmic reticulum stress

研究领域: 毒理学 · 分子生物学
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2025 · IF 6.1

The developmental toxicity of bisphenol F exposure on the zebrafish larvae

Biyu Wu,Zirui Cheng,Xiang Li,Minxing Liang,Xue Wang,Duan Pi,Jiayi Liu,Huiling Li,Jun Zhao,Junjie Wang,Fang Liang,Xuegeng Wang

As a major substitute for the bisphenol A (BPA), the use of the bisphenol F (BPF) has increased dramatically in recent years. Growing evidence suggest that BPF shares numerous toxicological properties with BPA, raising the concerns about its potential impact on the health of organisms. However, the developmental toxicity of BPF remains poorly understood. In this study, we conducted a 5-day BPF exposure experiment on zebrafish ( Danio rerio ) from blastula stage at concentrations of 2, 20, 200, and 2000 µg/L. Our results demonstrated a significant increase in hatching rates across all treatment groups at 2 days post-fertilization (dpf). The esr1 was significantly upregulated at 2000 µg/L by 5 dpf, while no significant change was observed in ar . The frequency of operculum loss significantly increased at exposure concentrations of 20, 200, and 2000 µg/L, and a notable increase in notochord loss was observed at 2000 µg/L. To explore the underlying mechanisms, transcriptomic analysis was performed to identify differentially expressed genes (DEGs). GO and KEGG pathway enrichment analysis revealed that the toxic effects of BPF were closely associated with osteoclast differentiation, the FoxO signaling pathway, and the MAPK signaling pathway. These pathways influenced critical biological processes, including response to stimuli, animal organ morphogenesis, detoxification, and biomineralization. This study provides evidence that BPF exposure at environmentally relevant concentrations (2 µg/L) is harmful to hatching, concentrations above 20 µg/L exhibit estrogenic-disrupting activity and exert toxicological effects on the development of the head skeleton in zebrafish. These effects are particularly linked to disruptions in osteoclast differentiation.

CAS / MDL: 620-92-8
研究领域: 环境毒理学 · 分子生物学
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TOXICOLOGY LETTERS · 2023 · IF 3.5

Genetic and prenatal developmental evaluation of anthraquinone

Jingjing Qu,Yinjing Zhang,Chunxia Liu,Qianqian Xie,Tong Ou,Bolin Fan,Yan Song

Anthraquinone is a recently identified contaminant present in teas globally, and its potential teratogenic and genotoxic impacts have yet to be fully comprehended. Hence, this study's objective was to determine anthraquinone's genotoxicity using various studies such as the Ames test , Mammalian erythrocyte micronucleus test, and in-vitro mammalian chromosome aberration study. Additionally, the study assessed its effects on maternal gestational toxicity and the fetus's teratogenicity through prenatal developmental toxicity research in rats. Results indicated that anthraquinone did not manifest mutagenic effects on Salmonella typhimurium histidine-deficient, did not cause chromosomal aberrations in Chinese hamster ovary cell subclone CHO-K1, and did not exhibit a genotoxic effect on mouse bone marrow erythrocytes. However, in the prenatal developmental toxicity study, administering anthraquinone orally to pregnant rats from day 5 to day 19 of gestation resulted in decreased body weight and food consumption of pregnant rats, along with a higher number of visceral malformations in the fetuses in the highest dose group (217.6 mg/kg BW). Additionally, two pregnant rats died in this group. The study has established the no observed adverse effect level (NOAEL) as 21.76 mg/kg BW, while the lowest observed adverse effect level (LOAEL) was 217.6 mg/kg BW.

CAS / MDL: 90-45-9
研究领域: 毒理学 · 遗传学 · 生殖医学
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PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY · 2024 · IF 4.2

Developmental effects of fenpropathrin on zebrafish (Danio rerio) embryo-larvae: Toxic endpoints and potential mechanism

Junguo Ma,Chunyu Diao,Yidan Zhang,Huan Kang,Yiyi Feng,Yuanyuan Li,Xiaoyu Li

Fenpropathrin (FEN), a highly efficient and broad-spectrum synthetic pyrethroid insecticide. Although sufficient concern has been given to the negative impacts of FEN on non-target organisms, limited knowledge exists regarding the developmental effects of FEN. In this study, effects of FEN (0.45, 1.35, 4.05, and 12.15 μg/L) on various early life-stage endpoints of zebrafish were investigated from 3 to 144 h post-fertilization (hpf) in order to disclose the developmental effects and underlying mechanisms caused by FEN. The results indicate that exposure to FEN induced developmental toxicity in zebrafish, including decreased heart rate, reduced blood flow, shorter body length, smaller eye size, non-inflated swim bladder, and disrupted craniofacial chondrogenesis, which were possibly due to a significant decrease in the levels of thyroxine (T4), triiodothyronine (T3), insulin-like growth factor-1 (IGF-1), and growth hormone (GH), increase in lipid accumulation, and alteration in the contents of total cholesterol (T-CHO) and triglyceride (TG) in larvae exposed to FEN. Besides, FEN exposure also resulted in the inhibition of spontaneous movement of embryo at 24 hpf, a decline in touch evoke response (TER) at 72 hpf, and a reduction in free-swimming activity at 144 hpf, as well as the larval activity at 144 hpf during the dark-light transition stimulus. Mechanistic examinations have shown that FEN treatment inhibits the activities of AChE and elevates the ACh levels. In addition, FEN exposure increased ROS levels and altered the levels of malondialdehyde (MDA), and induced apoptosis as determined by acridine orange staining and elevated caspase-3 levels, suggesting that the involvement of oxidative stress and apoptosis in FEN-induced developmental toxicity of embryos. Transcriptome sequencing of larvae showed that FEN altered the expressions of multiple metabolic and nervous system pathways, including PPAR signaling pathway, lipid metabolism pathway, carbohydrate metabolism pathway, retinol metabolism pathway, and neuroactive ligand-receptor interaction pathway, demonstrating that FEN alters the normal development of zebrafish embryos, and multiple pathways mediating the FEN-induced developmental toxicity. Overall, these findings enhance our understanding of the developmental toxic effects of FEN and provide fundamental data for assessing the risk of FEN on non-target organisms.

CAS / MDL: 886-86-2
研究领域: 环境科学 · 毒理学 · 分子生物学
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ENVIRONMENTAL POLLUTION · 2024 · IF 7.6

Mechanistic insight into the neurodevelopmental toxicity of the novel pesticide pyrifluquinazon (PFQ) and its major metabolite in early-life stage zebrafish

Rui Huang,Zijun Liu,Yunrui Pan,Zheng Ma,Huili Wang,Bin Wan,Jianzhong Li,Jing Chang

Pyrifluquinazon (PFQ), a novel insecticide containing a heptafluoroisopropyl moiety, has seen increasing use. However, limited research has been conducted on the toxicological effects and mechanisms of PFQ in aquatic organisms. To investigate the toxicity and underlying mechanisms of PFQ and its primary metabolite dPFQ in aquatic organisms, morphological, behavioral, hormonal, multi-omics analyses, and molecular docking studies were conducted on zebrafish larvae after exposure. The results showed that both PFQ and dPFQ induced developmental abnormalities, behavioral impairment, hormonal disruptions, and alterations in neurologically related metabolites and gene expression in early-stage zebrafish. Notably, delayed retinal vascular development was observed, which is also likely linked to the neurodevelopmental toxicity. Subsequently, identification and relative quantification of PFQ metabolites suggested that its toxicity might be primarily attributed to dPFQ. Finally, an Adverse Outcome Pathway (AOP) was proposed, initiating with the binding of dPFQ to the TRPV4 protein and ultimately leading to neurodevelopmental toxicity. This study delineated the neurodevelopmental toxicity of PFQ and its toxicological mechanisms in zebrafish, emphasizing the hazards posed by pesticide metabolites to non-target organisms and highlighting inherent limitations of extrapolating in vitro toxicity experiments.

CAS / MDL: 67-68-5
研究领域: 毒理学 · 环境科学 · 分子生物学
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ENVIRONMENTAL RESEARCH · 2025 · IF 7.7

ADB-FUBINACA-induced developmental toxicity, neurotoxicity, and cardiotoxicity in embryonic zebrafish (Danio rerio)

Yuanzhao Wu,Fengjun Fan,Lu Zhou,Yihang Shen,Anli Wang,Yazhou Qin,Jiye Wang,Weixuan Yao

As an emerging pollutant, the synthetic cannabinoid N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (ADB-FUBINACA) is widely abused and frequently detected in metropolitan wastewater. However, its effect on aquatic organisms remains unexplored. In this study, embryonic and larval zebrafish were exposed to sublethal concentrations of ADB-FUBINACA to assess its toxic effects via behavioral, biochemical, and metabolomic analyses. The observed morphological defects included reduced heartbeat, shorter body length, spinal deformation, and pericardial edema. Transgenic zebrafish exhibited cardiac developmental defects and apoptosis, indicating that cardiotoxicity is associated with dysregulated gene expression. Impaired motor activity and disrupted neuronal development suggested neurotoxicity. Elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels indicate oxidative stress, whereas transcriptional changes in immune-related genes reflect a dysregulated inflammatory response. Metabolomic analyses revealed disruptions in pathways related to alanine, purine, and pyrimidine metabolism, and arginine biosynthesis, which correlated with oxidative damage, cardiotoxicity, and neurodevelopmental effects. In conclusion, ADB-FUBINACA induces developmental toxicity in zebrafish embryos via oxidative stress and metabolic disruption, highlighting the potential environmental risks posed by this emerging pollutant.

CAS / MDL: 886-86-2
研究领域: 环境科学 · 毒理学 · 分子生物学
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CHEMOSPHERE · 2020 · IF 5.778

Exposure to prothioconazole induces developmental toxicity and cardiovascular effects on zebrafish embryo

Yongqi Sun,Yi Cao,Lili Tong,Fangyi Tao,Xiaonan Wang,Huiming Wu,Mengcen Wang

Prothioconazole is a fungicide that has been widely used in general agriculture and livestock husbandry. This study evaluated the acute toxicity of prothioconazole to zebrafish embryos by assessing their hatching rate and malformation when exposed to different concentrations of prothioconazole. The 96 h-LC 50 value of zebrafish embryos was 1.70 mg/L. Upon exposure to 0.85 mg/L, the mortality rate of the embryos significantly increased while their hatching rate decreased significantly. At prothioconazole concentrations higher than 0.43 mg/L, developmental morphologic abnormalities such as heart and yolk-sac edema, spine curvature, tail deformity, shortened body length and decreased eye area were observed. The heart rate of embryos decreased in a dose-dependent fashion during the exposure time. Prothioconazole exposure also resulted in increased rates of cardiac malformation detected by significant increase in the distance between the sinus venosus and bulbus arteriosus and the pericardium area. Moreover, the expression levels of genes related to cardiac development ( amhc, vmhc, fli1, hand2, gata4, nkx2.5, tbx5 and atp2a2a ) were significantly altered after exposure to prothioconazole. Indeed, this study revealed the adverse effects on the developmental and cardiovascular system of zebrafish embryo caused by prothioconazole. It further elucidated the risk of prothioconazole exposure to vertebrate cardiovascular toxicity. As such, it provides a theoretical foundation for pesticide risk management measures.

研究领域: 毒理学 · 环境科学 · 分子生物学
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2023 · IF 6.8

Developmental neurotoxic effects of bisphenol A and its derivatives in Drosophila melanogaster

Jie Wang,Chunyan Wu,Xing Zhang,Yuanyuan Song,Binquan Wang,Ke Zhang,Mingkuan Sun

As a result of the ban on bisphenol A (BPA), a hormone disruptor with developmental neurotoxicity, several BPA derivatives (BPs) have been widely used in industrial production. However, there are no effective methods for assessing the neurodevelopmental toxic effects of BPs. To address this, a Drosophila exposure model was established, and W 1118 was reared in food containing these BPs. Results showed that each BPs displayed different semi-lethal doses ranging from 1.76 to 19.43 mM. Exposure to BPs delayed larval development and affected axonal growth, resulting in the abnormal crossing of the midline of axons in the β lobules of mushroom bodies, but the damage caused by BPE and BPF was relatively minor. BPC, BPAF, and BPAP have the most significant effects on locomotor behavior, whereas BPC exhibited the most affected social interactions. Furthermore, exposure to high-dose BPA, BPC, BPS, BPAF, and BPAP also significantly increased the expression of Drosophila estrogen-related receptors. These demonstrated that different kinds of BPs had different levels of neurodevelopmental toxicity, and the severity was BPZ > BPC and BPAF > BPB > BPS > BPAP ≈ BPAl ≈ BPF > BPE. Therefore, BPZ, BPC, BPS, BPAF, and BPAP should be evaluated as potential alternatives to BPA.

研究领域: 毒理学 · 神经生物学
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2025 · IF 6.1

Acute exposure of perchlorate on zebrafish larvae: Neurotoxicity during development

Xiaoran Xue,Zaiqiu Zhang,Yang Yang,Lin Hu,Mingyi Zhao,Qingnan He

Objective This study aimed to assess the acute developmental toxicity of perchlorate exposure and identify its manifestation of neurotoxicity in zebrafish (Danio rerio) model. Methods Zebrafish larvae were exposed to sodium perchlorate at early developmental stages and the phenotypes of various developmental abnormalities were observed and recorded. Neurodevelopmental toxicity has been studied in particular in terms of central nervous system apoptosis, peripheral motor abnormalities, and abnormal autonomic motor behavior. Samples were processed for pathological, transcriptomic, and PCR analyses. Results Acute exposure of zebrafish larvae to perchlorate resulted in developmental toxicity in a concentration-dependent manner. Heart rate abnormality (33 %), slow blood flow (37 %), abnormal size of liver (23 %), delayed yolk absorption (70 %), and abnormal body pigmentation (100 %) were observed in the 3.83 mg/mL group. Heart edema (10 %), heart rate abnormality (60 %), slow blood flow (67 %), abnormal size of liver (77 %), delayed yolk absorption (100 %), abnormalities in intestinal morphology (30 %), abnormal body pigmentation (100 %), and shorter body length (47 %) were observed in the 4.03 mg/mL group. Developmental neurotoxicity was characterized by brain apoptosis, damage to the central nervous system ( P  < 0.01) and peripheral motor neurons ( P  < 0.0001), and reduced autonomous motor distance ( P  < 0.01). Transcriptomic analysis revealed that c3a.1, c5, fga, fgb, and fgg were upregulated in the complement and coagulation cascades, and the mRNA levels of c3a.1, dusp1, slc2a6, purba, and klf9 were found upregulated in PCR. Conclusion Acute perchlorate exposure on zebrafish larvae caused various developmental toxicity in a concentration-dependent manner, notably neurotoxicity. We believed the immunological and inflammatory responses were involved.

CAS / MDL: 7601-89-0 9002-93-1
研究领域: 毒理学 · 发育生物学 · 神经科学
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Journal of Xenobiotics · 2024 ·Vol. 14 ·期 2 ·452-466 · IF 6.8

Effects of Acute and Developmental Exposure to Bisphenol S on Chinese Medaka (Oryzias sinensis)

Bingying Li,Yongsi Huang,Duan Pi,Xiang Li,Yafen Guo,Zhiying Liang,Xiaohong Song,Junjie Wang,Xuegeng Wang

Bisphenol S (BPS), one of the substitutes for bisphenol A (BPA), is widely used in various commodities. The BPS concentrations in surface water have gradually increased in recent years, making it a predominant bisphenol analogue in the aquatic environment and raising concerns about its health and ecological effects on aquatic organisms. For this study, we conducted a 96 h acute toxicity test and a 15-day developmental exposure test to assess the adverse effects of BPS exposure in Chinese medaka (Oryzias sinensis), a new local aquatic animal model. The results indicate that the acute exposure of Chinese medaka embryos to BPS led to relatively low toxicity. However, developmental exposure to BPS was found to cause developmental abnormalities, such as decreased hatching rate and body length, at 15 dpf. A transcriptome analysis showed that exposure to different concentrations of bisphenol S often induced different reactions. In summary, environmental concentrations of BPS can have adverse effects on the hatching and physical development of Chinese medaka, and further attention needs to be paid to the potential toxicity of environmental BPS.

CAS / MDL: 80-09-1
研究领域: 环境科学 · 毒理学 · 生态学
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Water · 2025 ·Vol. 17 ·期 16 ·2450 · IF 3

Sodium p-Perfluorous Nonenoxybenzene Sulfonate (OBS) Induces Developmental Toxicity Through Apoptosis in Developing Zebrafish Embryos: A Comparison with Perfluorooctane Sulfonate

Yilong Zou,Xueping Huang,Xianglian Wang,Manqing Xu,Yong Sun

Perfluorooctane sulfonate (PFOS) is a representative persistent organic pollutant that exerts toxic effects on aquatic organisms. As an alternative to PFOS, sodiump-perfluorous nonenoxybenzene sulfonate (OBS) has been frequently detected in aquatic environments and human tissues in recent years. However, its toxic effects on aquatic organisms and potential health risks to humans remain unclear. Zebrafish embryos are transparent and amenable to in vivo manipulation and observation. Therefore, in the present study, we investigated its developmental toxicity in zebrafish embryos, with PFOS as the positive control. We exposed zebrafish embryos to different concentrations of OBS (15, 20, and 25 mg/L) and PFOS (15 mg/L) for 2–168 h post fertilization (hpf) and then examined physiological and gene expression changes. At 24 hpf, spontaneous twitches in the 25 mg/L OBS group decreased to (5 ± 0.34)/min. By 48 hpf, the 20 mg/L OBS group’s hatching rate was (47.78 ± 2.22)%, significantly lower than the control. At 72 hpf, heart rates in both the PFOS and OBS groups were elevated, at 82 ± 0.6, 84.5 ± 0.5, 89.4 ± 0.3, and 93.7 ± 0.4, respectively. Similarly to PFOS, OBS induced developmental toxicity in zebrafish embryos. In addition, both OBS and PFOS exposure downregulated the expression level of anti-apoptotic Bcl-2 in zebrafish embryos, with a notable 0.53-fold decrease observed in the 25 mg/L OBS group. Conversely, they upregulated the expression levels of pro-apoptotic Bax, Caspase-3, and Caspase-9, with Caspase-3 expression increasing 1.14-, 1.5-, and 1.7-fold in the 15 mg/L PFOS, 20 mg/L OBS, and 25 mg/L OBS groups, respectively. These OBS- and PFOS-induced changes in gene expression increased apoptosis, suggesting that OBS can induce developmental toxicity in zebrafish embryos, and that its effect is comparable to that of PFOS. Therefore, considering its aquatic toxicity, measures aimed at limiting or remediating OBS pollution in the environment are necessary.

CAS / MDL: 1763-23-1
研究领域: 环境毒理学 · 发育生物学 · 分子毒理学 · 水生生态毒理学 · 环境污染与健康
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