Lurasidone Induces Developmental Toxicity and Behavioral Impairments in Zebrafish Embryos
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1277809 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Lurasidone, a second-generation antipsychotic, is widely used for treating schizophrenia and bipolar disorder due to its favorable metabolic profile. However, its potential developmental neurotoxicity remains poorly understood. This study investigated the effects of lurasidone on zebrafish embryos, combining morphological, behavioral, transcriptomic, and neurotransmitter analyses. Zebrafish embryos were exposed to lurasidone at 0, 0.4, 4, and 8 mg/L concentrations from 5 to 120 hours post-fertilization (hpf). Results revealed dose-dependent developmental toxicity, including reduced survival and hatching rates, shorter body length, and increased pericardial and yolk sac edema. Behavioral assessments showed significant impairments in locomotion and touch response, particularly at higher concentrations. Transcriptomic analysis identified 1,907 differentially expressed genes, with upregulation of circadian regulation pathways and downregulation of cell cycle and oxidative phosphorylation pathways. Neurotransmitter profiling indicated significant reductions in glutamate, dopamine, and GABA levels, suggesting disruptions in excitatory/inhibitory balance. These findings highlight lurasidone's potential neurodevelopmental risks, particularly during critical developmental periods. The study underscores the importance of further research to assess the safety of lurasidone in vulnerable populations, such as pregnant women and young patients.
2025-06-27 | GSE299985 | GEO
Project description:Succinate Dehydrogenase Inhibitors (SDHIs) have been used for decades, with new formulations cropping up as fungi evolve. Boscalid was introduced to United States agriculture in 2003 and was determined to be effective for fungal management and safe for aquatic discharge and human consumption. Recent studies have found Boscalid’s primary metabolite, M510F01, on crops and in irrigation runoff as well. However, limited information is available about the aquatic and developmental toxicity of M510F01. The goal of our study was to compare and contrast the developmental toxicity of Boscalid with its metabolite, M510F01. Zebrafish (AB, wild-type strain) embryos were exposed to Boscalid or M510F01 from 3-96 hours post fertilization (hpf) at concentrations of 0.03, 0.3, or 3 µg/L. Embryos were examined for aberrant morphologies at 96 hpf using microscopy. Boscalid exposures at concentrations of 3 µg/L increased incidence of blue sac disease by 72%, craniofacial malformation by 97%, pericardial edema by 69%, delayed swim bladder inflation by 35%, and yolk edema by 83% (p<0.001 for all morphologies). 3 µg/L M510F01 increased the incidence of blue sac disease by 25% and yolk edema by 17% (p=0.005). Additionally, Boscalid exposures at 3 µg/L indicated a significant effect on fish length at 96 hpf (p<0.05).To assess whether Boscalid and M510F01 impact Cytochrome P450 1a (Cyp1a) activity, embryos were exposed to Boscalid or M510F01 (0.03 µg/L) from 96-100 hpf concurrently to 7-ethoxyresorufin (EROD)—a fluorometric indicator of Cyp1a activity. There is no significant change in acute EROD activity for Boscalid or M510F01; however, chronic exposure of Boscalid and M510F01 at 0.03 µg/L indicated a significant decrease in Cyp1a activity in the gut and M510F01 additionally reflected a significant decrease in Cyp1a activity in the liver at 0.03 µg/L. RNA sequencing and pathway analysis were performed to assess the mechanisms of xenobiotic response to Boscalid and M510F01 exposures (0.03 µg/L). Boscalid significantly upregulated pathways involved in ATP production including oxidative phosphorylation, glycolysis, and TCA cycle. Overall, this research suggests that M510F01 exhibits reduced aquatic and developmental toxicity when compared to Boscalid.
2025-08-20 | GSE232317 | GEO
Project description:Toxicogenomic signatures associated with methylmercury induced developmental toxicity in the zebrafish embryos.
| PRJNA851283 | ENA
Project description:Dextromethorphan is widely used in over-the-counter cough and cold medications. Its efficacy and safety for infants and young children remains to be clarified. The present study was designed to use zebrafish as a model to investigate the potential toxicity of dextromethorphan during embryonic and larval development. Three sets of zebrafish embryos/larvae were exposed to dextromethorphan at 24, 48 and 72 h post fertilization (hpf), respectively, during the embryonic/larval development. Compared with the 48 and 72 hpf exposure sets, the embryos/larvae in the 24 hpf exposure set showed much higher mortality rates which increased in a dose-dependent manner. Bradycardia and reduced blood flow were observed for the embryos/larvae treated with increasing concentrations of dextromethorphan. Morphological effects of dextromethorphan exposure, including yolk sac and cardiac edema, craniofacial malformation, lordosis, non-inflated swim bladder and missing gill, were also more frequent and severe among zebrafish embryos/larvae exposed to dextromethorphan at 24 hpf. Whether the more frequent and severe developmental toxicity of dextromethorphan observed among the embryos/larvae in the 24 hpf exposure set, as compared with the 48 and 72 hpf exposure sets, is due to the developmental expression of the phase I and phase II enzymes involved in the metabolism of dextromethorphan remains to be clarified. A reverse transcription-polymerase chain reaction analysis, nevertheless, revealed developmental stage-dependent expression of mRNAs encoding SULT3 ST1 and SULT3 ST3, two enzymes previously shown to be capable of sulfating dextrorphan, an active metabolite of dextromethorphan.
| S-EPMC3515875 | biostudies-literature
Project description:Tanshinone IIA (Tan-IIA) is derived from the dried roots of Salvia miltiorrhiza Bunge, a traditional Chinese medicine. Although Salvia miltiorrhiza has been applied for many years, the toxicity of the mono-constituent of Salvia miltiorrhiza, tanshinone IIA, is still understudied. This study evaluated the cardiotoxicity and developmental malformations of Tan-IIA by using zebrafish normal embryos and dechorionated embryos. After treatment with Tan-IIA in different concentrations for four-day periods, obvious pericardial edema, spinal curvature, and even missing tails were observed in zebrafish embryos. The LC50 values in the dechorionated embryo group at 72 h post-fertilization (hpf) and 96 hpf were 18.5 μM and 12.8 μM, respectively, and the teratogenicity was manifested at a concentration of about 1 µM. The main endpoints of teratogenicity were scoliosis, malformation of tail, and pericardium edema. Our findings displayed the potential cardiotoxicity and severe impact on the abnormal development of Tan-IIA in zebrafish embryo at high concentrations, which may help avoid the risk of its clinical application.
| S-EPMC6154573 | biostudies-literature
Project description:Developmental toxicity of the fungicide Boscalid and primary metabolite M510F01 in zebrafish embryos
| PRJNA971601 | ENA
Project description:General anesthetics can cause neurological damage and long-term behavioral/cognitive impairment during fetal and early postnatal life. However, the adverse influence on embryo development induced by propofol is unclear. We used embryonic zebrafish to explore the effects of propofol on embryonic and larval growth and development, and the related apoptotic mechanism. Zebrafish embryos were immersed in propofol (1, 2, 3, 4, and 5 μg/ml) dissolved in E3 medium from 6 to 48 hours post fertilization (hpf). The survival rate, locomotion, heart rate, hatchability, deformity rate, and body length were analyzed at defined stages. Terminal deoxynucleotidyl transferase nick-end-labeling was used to detect zebrafish embryo apoptosis, and the expression levels of apoptosis-related genes were determined using quantitative real-time reverse transcription PCR and whole-mount in situ hybridization. Larvae at 48 hpf were anesthetized by immersion in E3 culture medium containing 2 μg/ml propofol, the reasonable anesthetic concentration for zebrafish embryos, which caused significant caudal fin dysplasia, light pigmentation, edema, hemorrhage, and spinal deformity, and decreased the hatchability, body length, and heart rate. The numbers of apoptotic cells in propofol-treated 12, 48 and 72 hpf embryos increased significantly, and the mRNA expression levels of intrinsic apoptosis pathway-related casp3a, casp3b, casp9, and baxb genes were upregulated, mainly in the head and tail. Propofol decreased apoptosis in the head and back of 24 hpf zebrafish, which was consistent with the mRNA expression analysis. Our findings demonstrated that zebrafish embryos and larvae exposed to propofol experienced developmental toxicity, which correlated with the intrinsic apoptosis pathway with casp3a, casp3b, casp9, and baxb as the key genes.
| S-EPMC10228783 | biostudies-literature
Project description:Increased availability of cannabis and cannabinoid-containing products necessitates the need for understanding how exposure to these compounds can affect development. Using cannabinoid receptor-null zebrafish (cnr1-/- and cnr2-/-), we conducted experiments to assess the roles of these receptors in ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD) developmental and behavioral toxicity. THC increased mortality and deformities (pericardial and yolk sac edemas, a reduction in size) in cnr1-/- and cnr2-/- fish. Conversely, CBD-induced malformations and mortality were significantly reduced in the cnr1-/- and cnr2-/- larvae. THC and CBD exposure caused significantly decreased larval behavior (96 hpf), however, decreased distance travelled was protected in the cnr1-/- and cnr2-/- fish, suggesting these receptors are responsible for mediating behavioral toxicity. Transcriptomic profiling in cnr+/+ embryos developmentally exposed to 4 μM THC or 0.5 μM CBD revealed that a significant portion of differentially expressed genes were targets of PPARγ, a predicted upstream regulator. In Cnr-positive embryos, co-exposure to the PPARγ inhibitor GW9662 and THC or CBD, there was increased toxicity compared to exposure with THC or CBD alone. Co-treatment in the cnr2-/- fish with GW9662 did not alter the CBD-induced decrease in activity. However, co-treatment with GW9662 did remove the protective effect observed in cnr1-/- fish treated to CBD alone. Collectively, these results indicate that PPARγ, Cnr1, and Cnr2 all play crucial roles in the developmental toxicity of THC and CBD.
2021-01-01 | GSE164128 | GEO
Project description:Carpesii Fructus, the dried fruit of Carpesium abrotanoides L., has been used as a traditional Chinese medicine for centuries to kill intestinal parasites in children. It has been recorded as a mildly toxic medicine in the Chinese pharmacopoeia. However, little proof of its toxicology has been reported in modern pharmacology. This study investigated for the first time its developmental toxicity on zebrafish embryos/larvae from 6 to 96 h post-fertilization (hpf). In addition, the enzymes and genes associated with oxidative stress and apoptosis were tested to investigate the potential toxicologic mechanism preliminarily. The observation of toxicologic endpoints showed the developmental toxicity of Carpesii Fructus. Pericardial edema, yolk sac edema, bleeding tendency, and enlarged yolk were the most commonly occurring morphological changes observed in our study. According to the results of acridine orange staining and morphological observation, the developing heart was speculated to be the target organ of toxicity. Furthermore, Carpesii Fructus exposure changed the activities of defense enzymes, increased malondialdehyde (MDA) content, decreased caspase-3 activity, and altered mRNA levels of related genes (ogg1, p53, Cu/Zn-Sod, Mn-Sod, and Cat↓; Gpx↑) in zebrafish larvae, indicating that oxidative stress and additional apoptosis should have roles in the developmental toxicity of Carpesii Fructus. This is the first study that provides proof of modern pharmacology on the teratogenicity and possible toxicologic mechanism of Carpesii Fructus.
| S-EPMC6062322 | biostudies-literature
Project description:Carbendazim (CAR) and enrofloxacin (ENF) are frequently detected in fruits and meat products, respectively. Since most people consume fruits, vegetables, and meat products, combined exposure is possible, necessitating further evaluation of toxic interactions. In this study, the developmental toxicity of separate and combined exposure was examined in zebrafish embryos. Carbendazim exposure at 0.79 mg/L and above significantly affected developmental parameters, while enrofloxacin alone had no substantial effects on these developmental parameters within the selected concentration range (0.10-0.40 mg/L). Surprisingly, ENF antagonized the CAR-evoked reduction in the 48 hpf (hours post-fertilization) hatching rate and the increases in the 96 hpf malformation and lethality rates. The results revealed that the antagonism might be associated with reciprocal effects of these compounds on metabolism-related genes, such as cyp7a1 and apoa1a. These results reveal a complex interaction between ENF and CAR on metabolic regulation during development and highlight the importance of combined assessment for agents with the potential for simultaneous exposure.
| S-EPMC8704853 | biostudies-literature