Isavuconazole Induces Neurodevelopment Defects and Motor Behaviour Impairment in Zebrafish Larvae.

Isavuconazole is a broad-spectrum antifungal drug used for the treatment of serious infections caused by invasive aspergillosis and mucormycosis in adults. With the continuous use of this drug, its safety and environmental impact have received increasing attention. However, information on the adverse effects of the drug is very limited. Fish is a particularly important model for assessing environmental risks. In this study, the aquatic vertebrate zebrafish was used as a model to study the toxic effects and mechanisms of isavuconazole. We exposed zebrafish embryos to 0.25, 0.5, and 1 mg/L of isavuconazole 6 h after fertilization. The results showed that at 72 hpf, isavuconazole exposure reduced heart rate, body length, and survival of zebrafish embryos compared to controls. Secondly, when isavuconazole reached a certain dose level (0.25 mg/L), it caused morphological changes in the Tg(elavl3:eGFP) transgenic fish line, with the head shrunk, the body bent, the fluorescence intensity becoming weaker, the abnormal motor behaviour, etc. At the same time, exposure of zebrafish embryos to isavuconazole downregulated acetylcholinesterase (AchE) and adenosine triphosphate (ATPase) activities but upregulated oxidative stress, thereby disrupting neural development and gene expression of neurotransmitter pathways. In addition, astaxanthin partially rescued the neurodevelopmental defects of zebrafish embryos by downregulating oxidative stress. Thus, our study suggests that isavuconazole exposure may induce neurodevelopment defects and behavioural disturbances in larval zebrafish.

Case report: One case of acute myeloid leukemia M3 with atypical morphology.

Acute promyelocytic leukemia (APL) is a type of acute myeloid leukemia. About 2% of APL is characterized by atypical rearrangements. Here we reported one APL case with atypical manifestations and morphology. A 35-year-old woman patient, mainly due to fatigue, poor appetite for over 10 days and intermittent fever for 3 days. combined with the results of flow cytometry, fusion gene and chromosome, the patient was diagnosed as AML-M3 with atypical morphology. Double induction therapy with retinoic acid and arsenous acid was immediately administrated. Idarubicin was administrated on the 18th day. A re-examination was performed in the 5th week, both the blood routine test and myelogram showed normal results, and the fusion gene turned negative, indicating complete remission. When atypical morphology occurs, peripheral blood POX staining may be performed to check the abnormal cells. Flow cytometry, chromosome analysis, and fusion gene analysis are also required for further diagnosis.

Pinoresinol diglucoside mitigates dexamethasone-induced osteoporosis and chondrodysplasia in zebrafish.

BACKGROUND: The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly. OBJECTIVE: This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of Eucommia ulmoides, against dexamethasone-induced osteoporosis and chondrodysplasia. METHODS: A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone. The impact of PDG on bone mineralization was assessed through alizarin red and calcein staining. Alkaline phosphatase activity was quantified to evaluate osteoblast function. The influence of PDG on chondrogenesis was estimated using alcian blue staining. Fluorescence imaging and motor behavior analysis were employed to assess the protective effect of PDG on the structure and function of dexamethasone-induced skeletal teratogenesis. qPCR determined the expression of osteogenesis and Wnt signaling-related genes. Molecular docking was used to assess the potential interactions between PDG and Wnt receptors. RESULTS: PDG significantly increased bone mineralization and corrected spinal curvature and cartilage malformations in the zebrafish model. Furthermore, PDG enhanced swimming abilities compared to the model group. PDG mitigated dexamethasone-induced skeletal abnormalities in zebrafish by upregulating Wnt signaling, showing potential interaction with Wnt receptors FZD2 and FZD5. CONCLUSION: PDG mitigates dexamethasone-induced osteoporosis and chondrodysplasia by promoting bone formation and activating Wnt signaling.

Comparison of cardiotoxicity induced by alectinib, apatinib, lenvatinib and anlotinib in zebrafish embryos.

Four tyrosine kinase inhibitors, alectinib, apatinib, lenvatinib and anlotinib, have been shown to be effective in the treatment of clinical tumors, but their cardiac risks have also raised concerns. In this study, zebrafish embryos at 6 h post fertilization (hpf) were exposed to the four drugs at concentrations of 0.05-0.2 mg/L until 72 hpf, and then the development of these embryos was quantified, including heart rate, body length, yolk sac area, pericardial area, distance between venous sinus and balloon arteriosus (SV-BA), separation of cardiac myocytes and endocardium, gene expression, vascular development and oxidative stress. At the same exposure concentrations, alectinib and apatinib had little effect on the cardiac development of zebrafish embryos, while lenvatinib and anlotinib could induce significant cardiotoxicity and developmental toxicity, including shortened of body length, delayed absorption of yolk sac, pericardial edema, prolonged SV-BA distance, separation of cardiomyocytes and endocardial cells, and downregulation of key genes for heart development. Heart rate decreased in all four drug treatment groups. In terms of vascular development, alectinib and apatinib did not inhibit the growth of embryonic intersegmental vessels (ISVs) and retinal vessels, while lenvatinib and anlotinib caused serious vascular toxicity, and the inhibition of anlotinib in vascular development was more obvious. Besides, the level of reactive oxygen species (ROS) in the lenvatinib and anlotinib treatment groups was significantly increased. Our results provide reference for comparing the cardiotoxicity of the four drugs.

Dimethyl fumarate induces cardiac developmental toxicity in zebrafish via down-regulation of oxidative stress.

Dimethyl fumarate (DMF) is an immunosuppressant commonly used to treat multiple sclerosis and other autoimmune diseases. Despite known side effects such as lymphopenia, the effect of DMF on cardiac development remains unclear. To assess this, we used zebrafish to evaluate the cardiac developmental toxicity of DMF. Our study showed that DMF reduced the survival rate of zebrafish embryos, with those exposed to 1, 1.3, and 1.6 mg/L exhibiting heart rate reduction, shortened body length, delayed yolk sac absorption, pericardial edema, increased distance from sinus venous to bulbus arteriosus, and separation of cardiomyocytes and endocardial cells at 72 hpf. Heart development-related genes showed disorder, apoptosis-related genes were up-regulated, and the oxidative stress response was down-regulated. Treatment with cysteamine ameliorated the heart development defects. Our study demonstrates that DMF induces cardiac developmental toxicity in zebrafish, possibly by down-regulating oxidative stress responses. This study provides a certain research basis for further study of DMF-induced cardiac developmental toxicity, and provides some experimental evidence for future clinical application and study of DMF.

Iprodione induces hepatotoxicity in zebrafish by mediating ROS generation and upregulating p53 signalling pathway.

Iprodione is an effective and broad-spectrum fungicide commonly used for early disease control in fruit trees and vegetables. Due to rainfall, iprodione often finds its way into water bodies, posing toxicity risks to non-target organisms and potentially entering the human food chain. However, there is limited information available regarding the developmental toxicity of iprodione specifically on the liver in existing literature. In this study, we employed larval and adult zebrafish as models to investigate the toxicity of iprodione. Our findings revealed that iprodione exposure led to yolk sac edema and increased mortality in zebrafish. Notably, iprodione exhibited specific effects on zebrafish liver development. Additionally, zebrafish exposed to iprodione experienced an overload of reactive oxygen species, resulting in the upregulation of p53 gene expression. This, in turn, triggered hepatocyte apoptosis and disrupted carbohydrate/lipid metabolism as well as energy demand systems. These results demonstrated the substantial impact of iprodione on zebrafish liver development and function. Furthermore, the application of astaxanthin (an antioxidant) and p53 morpholino partially mitigated the liver toxicity caused by iprodione. To summarize, iprodione induces apoptosis through the upregulation of p53 mediated by oxidative stress signals, leading to liver toxicity in zebrafish. Our study highlights that exposure to iprodione can result in hepatotoxicity in zebrafish, and it may potentially pose toxicity risks to other aquatic organisms and even humans.

BPA induces hepatotoxicity in zebrafish through oxidative stress and apoptosis pathways.

BPA is so ubiquitous that 27 million tons of BPA-containing plastic, including mineral water bottles and baby bottles, is produced worldwide each year. The potential toxicity of BPA to humans and aquatic organisms has been the subject of intense research. In this study, a zebrafish model system was used to assess BPA-mediated hepatotoxicity. Zebrafish larvae at 72-144 hpf were exposed to BPA at different concentrations (0,1, 3 and 5mg/L). For example, BPA-treated zebrafish larvae showed increased mortality, delayed uptake of nutrients in yolk sac, shortened body length, smaller liver area, abnormal expression of genes related to liver development, and pathological changes in the liver tissue. Mechanistically, BPA exposure induced excessive oxidative stress in the liver of zebrafish and increased the level of hepatocyte apoptosis in zebrafish larvae, and the antioxidant astaxanthin could rescue the BPA-mediated liver toxicity.

Benzophenone induces cardiac developmental toxicity in zebrafish embryos by upregulating Wnt signaling.

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 ß-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.

Apatinib induces zebrafish hepatotoxicity by inhibiting Wnt signaling and accumulation of oxidative stress.

Apatinib, a small-molecule VEGFR2-tyrosine kinase inhibitor, has shown potent anticancer activity in various clinical cancer treatments, but also different adverse reactions. Therefore, it is necessary to study its potential toxicity and working mechanism. We used zebrafish to investigate the effects of apatinib on the development of embryos. Zebrafish exposed to 2.5, 5, and 10 µM apatinib showed adverse effects such as decreased liver area, pericardial oedema, slow yolk absorption, bladder atrophy, and body length shortening. At the same time, it leads to abnormal liver tissue structure, liver function and related gene expression. Furthermore, after exposure to apatinib, oxidative stress levels were significantly elevated but liver developmental toxicity was effectively ameliorated with oxidative stress inhibitor treatment. Apatinib induces down-regulation of key target genes of Wnt signaling pathway in zebrafish, and it is found that Wnt activator can significantly rescue liver developmental defects. These results suggest that apatinib may induce zebrafish hepatotoxicity by inhibiting the Wnt signaling pathway and up-regulating oxidative stress, helping to strengthen our understanding of rational clinical application of apatinib.

Cysteamine hydrochloride affects ocular development and triggers associated inflammation in zebrafish.

The increasing use of cosmetics has raised widespread concerns regarding their ingredients. Cysteamine hydrochloride (CSH) is a newly identified allergenic component in cosmetics, and therefore its potential toxicity needs further elucidation. Here, we investigated the in vivo toxicity of CSH during ocular development utilizing a zebrafish model. CSH exposure was linked to smaller eyes, increased vasculature of the fundus and decreased vessel diameter in zebrafish larvae. Moreover, CSH exposure accelerated the process of vascular sprouting and enhanced the proliferation of ocular vascular endothelial cells. Diminished behavior in response to visual stimuli and ocular structural damage in zebrafish larvae after CSH treatment were confirmed by analysis of the photo-visual motor response and pathological examination, respectively. Through transcriptional assays, transgenic fluorescence photography and molecular docking analysis, we determined that CSH inhibited Notch receptor transcription, leading to an aberrant proliferation of ocular vascular endothelial cells mediated by Vegf signaling activation. This process disrupted ocular homeostasis, and induced an inflammatory response with neutrophil accumulation, in addition to the generation of high levels of reactive oxygen species, which in turn promoted the occurrence of apoptotic cells in the eye and ultimately impaired ocular structure and visual function during zebrafish development.

Pexidartinib hydrochloride exposure induces developmental toxicity and immunotoxicity in zebrafish embryos via activation of Wnt signaling.

Pexidartinib, a macrophage colony-stimulating factor receptor (CSF-1R) inhibitor, is indicated for the treatment of tendon sheath giant cell tumor (TGCT). However, few studies on the toxicity mechanisms of pexidartinib for embryonic development. In this study, the effects of pexidartinib on embryonic development and immunotoxicity in zebrafish were investigated. Zebrafish embryos at 6 h post fertilization (6 hpf) were exposed to 0, 0.5, 1.0, and 1.5 µM concentrations of pexidartinib, respectively. The results showed that different concentrations of pexidartinib induced the shorter body, decreased heart rate, reduced number of immune cells and increase of apoptotic cells. In addition, we also detected the expression of Wnt signaling pathway and inflammation-related genes, and found that these genes expression were significantly upregulated after pexidartinib treatment. To test the effects of embryonic development and immunotoxicity due to hyperactivation of Wnt signaling after pexidartinib treatment, we used IWR-1, Wnt inhibitor, for rescue. Results show that IWR-1 could not only rescue developmental defects and immune cell number, but also downregulate the high expression of Wnt signaling pathway and inflammation-related caused by pexidartinib. Collectively, our results suggest that pexidartinib induces the developmental toxicity and immunotoxicity in zebrafish embryos through hyperactivation of Wnt signaling, providing a certain reference for the new mechanisms of pexidartinib function.

Sanguinarine exposure induces immunotoxicity and abnormal locomotor behavior in zebrafish.

Sanguinarine (C20H14NO4+), a plant alkaloid and pesticide, works well a fungicidal and insecticidal applications. The prospect that sanguinarine may have potentially toxic effects on aquatic organisms has been brought to light by its use in agriculture. The first evaluation of the immunotoxic and behavioral effects of sanguinarine exposure on larval zebrafish was done in this work. Firstly, zebrafish embryos exposed to sanguinarine had shorter body length, larger yolk sacs, and slower heart rates. Secondly, the number of innate immune cells was significantly reduced. Thirdly, alterations in locomotor behavior were observed as exposure concentrations increased. Total distance travelled, travel time, and mean speed were all reduced. We also found significant changes in oxidative stress-related indicators and a significant increase in apoptosis in the embryos. Further studies revealed aberrant expression of some key genes in the TLR immune signaling pathway including CXCL-c1c, IL8, MYD88, and TLR4. At the same time, the expression of the pro-inflammatory cytokine IFN-γ was upregulated. To sum up, our results suggest that sanguinarine exposure may cause immunotoxicity and aberrant behavior in larval zebrafish.

Hepatic lipid metabolism disorders and immunotoxicity induced by cysteamine in early developmental stages of zebrafish.

Cysteamine, a sulfhydryl compound, is an intermediate in the metabolism of coenzyme A to taurine in living organisms. However, the potential side effects of cysteamine such as hepatotoxicity in pediatric patients have been reported in some studies. To evaluate the impact of cysteamine on infants and children, larval zebrafish (a vertebrate model) were exposed to 0.18, 0.36 and 0.54 mM cysteamine from 72 hpf to 144 hpf. Alterations in general and pathological evaluation, biochemical parameters, cell proliferation, lipid metabolism factors, inflammatory factors and Wnt signaling pathway levels were examined. Increased liver area and lipid accumulation were observed in liver morphology, staining and histopathology in a dose-dependent manner with cysteamine exposure. In addition, the experimental cysteamine group exhibited higher alanine aminotransferase, aspartate aminotransferase, total triglyceride and total cholesterol levels than the control group. Meanwhile, the levels of lipogenesis-related factors ascended whereas lipid transport-related factors descended. Oxidative stress indicators such as reactive oxygen species, MDA and SOD were upregulated after cysteamine exposure. Afterwards, transcription assays revealed that biotinidase and Wnt pathway-related genes were upregulated in the exposed group, and inhibition of Wnt signaling partially rescued the abnormal liver development. The current study found that cysteamine-induced hepatotoxicity in larval zebrafish is due to inflammation and abnormal lipid metabolism, which is mediated by biotinidase (a potential pantetheinase isoenzyme) and Wnt signaling. This provides a perspective on the safety of cysteamine administration in children and identifies potential targets for protection against adverse reactions.

Roxadustat induces hepatotoxicity in zebrafish embryos via inhibiting Notch signaling.

Roxadustat is a novel and effective small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PHI). However, little research has been done on its toxicity to vertebrate embryonic development. In this study, we used zebrafish to assess the effects of roxadustat on early embryonic development. Exposure to 14, 28, and 56 µM roxadustat resulted in abnormal embryonic development in zebrafish embryos, such as shortened body length and early liver developmental deficiency. Roxadustat exposure resulted in liver metabolic imbalance and abnormal liver tissue structure in adult zebrafish. In addition, roxadustat could up-regulate oxidative stress, and astaxanthin (AS) could partially rescue liver developmental defects by down-regulation of oxidative stress. After exposure to roxadustat, the Notch signaling is down-regulated, and the use of an activator of Notch signaling can partially rescue hepatotoxicity. Therefore, our research indicates that roxadustat may induce zebrafish hepatotoxicity by down-regulating Notch signaling. This study provides a reference for the clinical use of roxadustat.

Cyclosporine A induces hepatotoxicity in zebrafish larvae via upregulating oxidative stress.

As a powerful immunosuppressant, cyclosporine A (CsA) is widely used clinically. However, it has been found to have many side effects including nephrotoxicity and neurotoxicity. Despite this, some patients cannot avoid using CsA during pregnancy and this can be detrimental to both the patient and the foetus. This study used zebrafish as a model animal to evaluate the hepatotoxic effects of CsA in zebrafish embryos. Zebrafish embryos cultured at 72 post-fertilization (hpf) were exposed to three concentrations of CsA at 2.5 mg/L, 5 mg/L, and 10 mg/L for 72 h. Liver developmental defects, smaller or missing swim bladder, slower heart rate, reduced body length, and delayed yolk sac absorption were observed. The level of oxidative stress (ROS) increased with the increase of CsA concentration. The indicators of related oxidative stress kinase activities including malondialdehyde (MDA), catalase (CAT) and SOD, all appeared to significantly increased. The use of astaxanthin (ATX) to inhibit oxidative stress was found to be useful for rescuing zebrafish hepatic development defects. Therefore, our results suggest that CsA induces zebrafish embryonic hepatic development defects by activating the oxidative stress. The study of CsA-induced hepatic development defects of zebrafish embryos is helpful for clinical evaluation of the safety of CsA and enables the search for new use without side effects.

Hexafluoropropylene oxide trimer acid (HFPO-TA) disturbs embryonic liver and biliary system development in zebrafish.

Hexafluoropropylene oxide trimer acid (HFPO-TA), a novel alternative to perfluorooctanoic acid (PFOA), has emerged as a potential environmental pollutant. Here, to investigate the toxic effects of HFPO-TA on liver and biliary system development, zebrafish embryos were exposed to 0, 50, 100, or 200 mg/L HFPO-TA from 6 to 120 h post-fertilization (hpf). Results showed that the 50 % lethal concentration (LC50) of HFPO-TA was 231 mg/L at 120 hpf, lower than that of PFOA. HFPO-TA exposure decreased embryonic hatching, survival, and body length. Furthermore, HFPO-TA exerted higher toxicity at the specification stage than during the differentiation and maturation stages, leading to small-sized livers in Tg(fabp10a: DsRed) transgenic larvae and histopathological changes. Significant decreases in the mRNA expression of genes related to liver formation were observed. Alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) levels were significantly increased. HFPO-TA decreased total cholesterol (TCHO) and triglyceride (TG) activities, disturbed lipid metabolism through the peroxisome proliferator-activated receptor (PPAR) pathway, and induced an inflammatory response. Furthermore, HFPO-TA inhibited intrahepatic biliary development in Tg(Tp1:eGFP) transgenic larvae and interfered with transcription of genes associated with biliary duct development. HFPO-TA reduced bile acid synthesis but increased bile acid transport, resulting in disruption of bile acid metabolism. Therefore, HFPO-TA influenced embryonic liver and biliary system morphogenesis, caused liver injury, and may be an unsafe alternative for PFOA.

Propranolol hydrochloride induces neurodevelopmental toxicity and locomotor disorders in zebrafish larvae.

Propranolol hydrochloride is the first-line drug for the clinical treatment of hypertension, arrhythmia, and other diseases. However, with the increasing use of this drug, its safety and environmental health have received more and more attention. In this study, aquatic vertebrate zebrafish were used as a model to study the toxic effects and mechanisms of propranolol hydrochloride. It was revealed that zebrafish larvae exposed to propranolol hydrochloride showed aberrant head nerve development and locomotor disorders. Additionally, exposure to propranolol hydrochloride could induce oxidative stress, alter the activities of AChE and ATPase, and disrupt the expression of genes involved in neurodevelopment and neurotransmitter pathways. More interestingly, the expression of Parkinson's disease-related genes was altered in zebrafish treated with propranolol hydrochloride. We detected the expression of genes related to the Wnt signaling pathway and found that their expression appeared to be down-regulated. The phenotype of nerve developmental defects and locomotor disorders can be effectively rescued by astaxanthin and Wnt activators. Collectively, the results suggest that propranolol hydrochloride may induce neurotoxicity and abnormal movement behavior with PD-like symptoms in zebrafish larvae.

Exposure to pyrazosulfuron-ethyl induces immunotoxicity and behavioral abnormalities in zebrafish embryos.

Pyrazosulfuron-ethyl is one of the most widely used herbicides in agriculture and can be widely detected in aquatic ecosystems. However, its biosafety, including its potential toxic effects on aquatic organisms and its mechanism, is still poorly understood. As an ideal vertebrate model, zebrafish, the effect of pyrazosulfuron-ethyl on early embryonic development and immunotoxicity of zebrafish can be well evaluated. From 10 to 72 h post fertilization (hpf), zebrafish embryos were exposed to 1, 5, and 9 mg/L pyrazosulfuron-ethyl which led in a substantial reduction in survival, total length, and heart rate, as well as a range of behavioral impairments. In zebrafish larvae, the number of neutrophils and macrophages was considerably decreased and oxidative stress levels increased in a dose-dependent way after pyrazosulfuron-ethyl exposure. And the expression of immune-related genes, such as TLR-4, MyD88 and IL-1ß, were downregulated by pyrazosulfuron-ethyl exposure. Moreover, pyrazosulfuron-ethyl exposure also inhibited motor behavior. Notch signaling was upregulated after exposure to pyrazosulfuron-ethyl, while inhibition of Notch signaling pathway could rescue immunotoxicity. Therefore, our findings suggest that pyrazosulfuron-ethyl has the potential to induce immunotoxicity and neurobehavioral changes in zebrafish larvae.

Cysteamine affects skeletal development and impairs motor behavior in zebrafish.

Cysteamine is a kind of feed additive commonly used in agricultural production. It is also the only targeted agent for the treatment of cystinosis, and there are some side effects in clinical applications. However, the potential skeletal toxicity remains to be further elucidated. In this study, a zebrafish model was for the first time utilized to synthetically appraise the skeletal developmental defects induced by cysteamine. The embryos were treated with 0.35, 0.70, and 1.05 mM cysteamine from 6 h post fertilization (hpf) to 72 hpf. Substantial skeletal alterations were manifested as shortened body length, chondropenia, and abnormal somite development. The results of spontaneous tail coiling at 24 hpf and locomotion at 120 hpf revealed that cysteamine decreased behavioral abilities. Moreover, the level of oxidative stress in the skeleton ascended after cysteamine exposure. Transcriptional examination showed that cysteamine upregulated the expression of osteoclast-related genes but did not affect osteoblast-related genes expression. Additionally, cysteamine exposure caused the downregulation of the Notch signaling and activating of Notch signaling partially attenuated skeletal defects. Collectively, our study suggests that cysteamine leads to skeletal developmental defects and reduces locomotion activity. This hazard may be associated with cysteamine-mediated inhibition of the Notch signaling and disorganization of notochordal cells due to oxidative stress and apoptosis.

Pamiparib Induces Neurodevelopmental Defects and Cerebral Haemorrhage in Zebrafish Embryos via Inhibiting Notch Signalling.

Pamiparib is a poly ADP-ribose polymerase (PARP) inhibitor used in clinical studies, which can penetrate the blood-brain barrier efficiently. At present, there are few studies on its effect on vertebrate neurodevelopment. In this study, we exposed zebrafish embryos to 1, 2 and 3 µM of Pamiparib from 6 to 72 h post-fertilisation (hpf). Results showed that pamiparib can specifically induce cerebral haemorrhage, brain atrophy and movement disorders in fish larvae. In addition, pamiparib exposure leads to downregulation of acetylcholinesterase (AChE) and adenosine triphosphate (ATPase) activities, and upregulation of oxidative stress which then leads to apoptosis and disrupts the gene expression involved in the neurodevelopment, neurotransmitter pathways and Parkinson's disease (PD) like symptoms. Meanwhile, astaxanthin can partially rescue neurodevelopmental defects by downregulating oxidative stress. After exposure to pamiparib, the Notch signalling is downregulated, and the use of an activator of Notch signalling can partially rescue neurodevelopmental toxicity. Therefore, our research indicates that pamiparib may induce zebrafish neurotoxicity by downregulating Notch signalling and provides a reference for the potential neurotoxicity of pamiparib during embryonic development.