Pericardial Edema Research Articles

The Acute Toxicity and Cardiotoxic Effects of Levofloxacin on Zebrafish (Danio rerio)

Emerging contaminants refer to chemical substances that have not been widely regulated but possess the potential to cause adverse effects on both the environment and human health. Antibiotics, as emerging contaminants, pose significant threats to ecosystems and human health due to their widespread use and persistence in the environment. Levofloxacin, a broad-spectrum fluoroquinolone antibiotic, is commonly employed in the treatment of bacterial infections, and has been frequently detected in environmental matrices and freshwater systems. In this study, we assessed the effects of levofloxacin on hatchability, mortality rates, malformations, behavioral changes, and cardiac development in zebrafish embryos by exposing them to varying concentrations of levofloxacin (0, 0.5, 1, 2, 4, and 8 mM). Our results demonstrate that levofloxacin exposure significantly impaired the growth and development of zebrafish larvae, particularly at higher concentrations. Notable effects included reduced body length, abnormal yolk sac and swim bladder development, pericardial edema, prolonged distances between the sinus venosus and arteriolar bulb (SV-BA), and disruptions in heart rate. Quantitative PCR analysis further revealed that levofloxacin exposure significantly upregulated the expression of key cardiac development genes in zebrafish larvae, including nppa, myh6, cacna1ab, myl7, gata4, nkx2.5, tbx2b, and tbx5b. These findings indicate that levofloxacin exposure exerts significant toxic effects on both embryonic and larval growth as well as heart development and gene expression in zebrafish. This study provides critical insights into the potential ecological risks posed by levofloxacin along with other antibiotics while laying a foundation for further investigation into their toxicological mechanisms.

Exposure to the Polychlorinated biphenyl mixture Aroclor 1254 elicits neurological and cardiac developmental effects in early life stage zebrafish (Danio rerio).

The goal of this study was to compare the bioaccumulation of the PCB mixture Aroclor 1254 in zebrafish to cardiac and neurologic outcomes. The establishment of effect concentrations (ECs) for cardiac and neurotoxic effects of PCBs in early life stage fish is challenging due to a lack of measured PCB concentrations in test media (e.g., fish tissue), the lack of standard exposure methods, and the propensity of PCBs to adsorb to test glassware and materials resulting in discrepancies in ECs from different studies with similar endpoints. Reporting tissue concentrations in test organisms will allow for standardization across different tests and thus may improve estimations of effect thresholds. Early life stage zebrafish (Danio rerio) are a common environmental toxicological model well represented within the literature, making them ideal for comparisons across multiple studies. Embryos were exposed at 6h post fertilization (hpf) to aqueous Aroclor 1254 for 96h with or without renewal in addition to a PCB 126 positive control for cardiotoxicity. PCB concentrations were measured in both exposure solutions and tissue samples. Measured concentrations of Aroclor 1254 in test solutions ranged from 8.7% to 870% of nominal concentrations. Heart rate, pericardial edema, and neurological endpoints (eye tremors) were measured in 102 hpf larvae. Pericardial edema was not present in Aroclor 1254-treated zebrafish but was observed in those exposed to PCB-126. Concentration-dependent bradycardia was observed in zebrafish exposed to Aroclor 1254 and PCB-126. Similarly, a concentration-dependent increase in eye tremor behavior was observed in embryos exposed to Aroclor 1254. Data produced by this study demonstrate novel toxicological effects of Aroclor 1254 and highlight the importance of measuring PCBs in both exposure and receptor media.

Fluconazole induces cardiovascular toxicity in zebrafish by promoting oxidative stress, apoptosis, and disruption of key developmental genes.

This study systematically evaluated the toxic effects of fluconazole on the cardiovascular development of zebrafish. Zebrafish embryos were treated with different concentrations of fluconazole (200, 400, and 800μg/ml) to observe its impact on heart development, reactive oxygen species (ROS) generation, apoptosis, and hemoglobin production. The results showed that as the concentration of fluconazole increased, significant changes in zebrafish heart structure were observed, along with a notable reduction in heart rate. Pericardial edema and cardiac morphological abnormalities were particularly prominent in the high-dose group. In addition, fluconazole treatment significantly increased ROS levels and induced apoptosis in cardiac cells. Enzyme-linked immunosorbent assay (ELISA) results showed that fluconazole treatment significantly increased the malondialdehyde (MDA) content and reduced superoxide dismutase (SOD) and catalase (CAT) activity, suggesting that oxidative stress and cell death may play a key role in its cardiotoxicity. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that fluconazole treatment significantly affected the expression of several key genes related to heart development and function, particularly cardiac myosin light chain 2 (cmlc2), ventricular myosin heavy chain (vmhc), and myosin heavy chain 6 (myh6), whose expression changes were closely associated with alterations in heart morphology and function. Transcriptomic analysis showed that several signaling pathways related to cardiac development, apoptosis, and metabolism were affected. In summary, this study reveals the multifaceted cardiotoxic mechanisms of fluconazole in zebrafish and provides new insights into drug safety assessment.

Tetrachlorantraniliprole induces neurodevelopmental toxicity through oxidative stress-mediated apoptosis and dysregulation of Wnt signaling pathway.

Tetrachlorantraniliprole (TCTP) is a novel bisamide insecticide and widely used to protect against lepidopteran insect species. However, the application of TCTP in rice fields often leads to water pollution, posing threats to aquatic organisms and potentially to human health. Few studies have assessed the toxic effects of TCTP on aquatic animals. In this study, we used zebrafish as a model organism to evaluate the toxicity of TCTP. Our findings indicated that TCTP adversely affected the development of zebrafish larvae, impacting parameters such as heart rate, body length, and pericardial edema. Exposure to TCTP resulted in the increased embryo mortality along with higher concentrations of the compound. The expression of neurodevelopment-related genes was inhibited in embryos exposed to TCTP. Hematoxylin and eosin (HE) staining revealed that TCTP caused damage to the brain cells of the embryos. Behavioral analysis showed a reduction in activity of the larvaes, which aligned with a decrease in acetylcholinesterase (AChE) activity. Additionally, RNA sequencing (RNA-seq) was employed to elucidate the mechanisms of toxicity. GO and KEGG analysis identified that the pathways were related to oxidative stress, apoptosis and Wnt signaling. We observed an increase of reactive oxygen species (ROS) and Ca²/Mg²-ATPase activity, while antioxidant enzyme activities (SOD, MDA, CAT, Na/K-ATPase and T-ATPase) were significantly decreased in TCTP-exposed groups. Furthermore, TCTP induced brain cells apoptosis, as evidenced by the upregulation of pro-apoptotic genes (bax, p53, TNFα, caspase3 and caspase9) and the downregulation of anti-apoptotic gene (bcl2). Moreover, TCTP increased the expression of genes involved in Wnt signaling pathway. Notably, oxidative stress and neuronal damage induced by TCTP could be mitigated by astaxanthin, an antioxidant. Additionally, IWR-1, an inhibitor of Wnt signaling pathway, effectively alleviated the upregulation of genes associated with TCTP treatment and inhibited oxidative stress-induced apoptosis. In conclusion, this study demonstrated TCTP-induced defects of neurodevelopment and the brain cells in zebrafish larvae which were primarily driven by oxidative stress-induced apoptosis and dysregulation of Wnt signaling pathway. Importantly, these toxic phenotypes can be rescued by treatment with astaxanthin or IWR-1.

Metabolomics approach to evaluate diclazuril-induced developmental toxicity in zebrafish embryo.

Anticoccidials, commonly used in veterinary medicine to treat coccidiosis in food-producing animals, particularly in poultry farming, are associated with potential environmental risks due to their excretion in manure and subsequent land-spreading. Diclazuril, a widely used anticoccidial, has been detected in groundwater, raising concerns about its impact on non-target species. This study investigates the developmental toxicity of diclazuril in zebrafish embryos over a 96-hour exposure period, utilizing biomarkers such as oxidative stress indicators and metabolomic profiles. The acute toxicity assessment determined an LC50 of 255 µg/L for diclazuril. Observed sublethal effects included pericardial edema, curved spine, and yolk sac edema, which worsened with increasing concentrations from 106 µg/L to 515 µg/L. Based on the Lowest Observed Adverse Effect Level (LOAEL), further experiments were conducted at concentrations of 50 µg/L, 100 µg/L, and 200 µg/L. Significant increases in reactive oxygen species (ROS) were noted at 100 µg/L and 200 µg/L, alongside notable reduction in superoxide dismutase (SOD) and glutathione S-transferase (GST) activities at concentrations ≥100 µg/L, while no significant changes observed in catalase (CAT) activity. Metabolomic analysis using GC-MS/MS revealed significant disturbances in pathways such as pyruvate metabolism, the citric acid cycle, and amino acid metabolism, indicating potential mitochondrial dysfunction in groups exposed to concentrations ≥100 µg/L. Furthermore, alterations in histological lesions in brain region and altered neurotransmitter activity suggests possible neurobehavioral disorders. Increased oxidative stress, along with decreased ATP and NADH levels, points to mitochondrial dysfunction, which is further supported by ultrastructural analysis and locomotor behavior confirming mitochondrial disruption. The disruption of cellular energetics is likely a key factor contributing to the neurotoxic effects observed in zebrafish embryos exposed to ≥100 µg/L of diclazuril.

In vivo toxicological evaluation of 3-benzylideneindolin-2-one: antifungal activity against clinical isolates of dermatophytes

BackgroundDermatophytes, the primary causative agents of superficial cutaneous fungal infections in humans, present a significant therapeutic challenge owing to the increasing prevalence of recurrent infections and the emergence of antifungal resistance. To address this critical gap, this study was designed to investigate the antifungal potential of 3-benzylideneindolin-2-one against dermatophytes and assess its in vivo toxicological profile using brine shrimp and zebrafish embryo models.MethodsThe antifungal activity of 3-benzylideneindolin-2-one was evaluated against 30 clinical isolates of dermatophyte species, including Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum gypseum, Microsporum canis, and Epidermophyton floccosum, by determining the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) using the broth microdilution method. The fungicidal activity was evaluated using time-kill assays. Toxicological effects were investigated using the brine shrimp lethality assay to determine Artemia salina nauplii mortality after 48 h of exposure, and the fish embryo acute toxicity test, which assessed lethality and developmental abnormalities in zebrafish (Danio rerio) embryos over a 96 h post-fertilization period.Results3-Benzylideneindolin-2-one exhibited consistent fungicidal activity across all dermatophyte species, with MICs ranging from 0.25 to 8 mg/L and MFCs ranging from 1 to 32 mg/L. Time-kill assays revealed a concentration-dependent fungicidal effect on the microconidia. The compound exhibited moderate toxicity to A. salina nauplii, with LC50 values of 69.94 mg/L and 52.70 mg/L at 24 and 48 h, respectively, while showing no significant lethality within the MIC range. In zebrafish embryos, concentrations below 7.5 mg/L did not significantly affect lethality, hatchability, or induce morphological abnormalities. However, at a concentration of 10 mg/L, the compound induced mild toxicity in embryos, evidenced by a significant increase in mortality and the presence of morphological anomalies such as yolk-sac and pericardial edema compared to the control group.ConclusionsThe consistent antifungal activity of 3-benzylideneindolin-2-one against clinically significant dermatophyte species, combined with its low toxicity within the therapeutic window, underscores its potential as a promising lead compound for the development of effective therapeutics for dermatophytosis.

Fish early-life stage toxicity and environmental relevance: What does high-dose toxicity testing tell us?

Abstract The early-life stage (ELS) toxicity syndrome for fish is well described and has been reported in hundreds of toxicity studies. It is generally characterized by a reduced heart rate, yolk sac and pericardial edemas, and various morphological abnormalities, the most common being spinal curvature. For many of those studies it appears that the ELS toxicity syndrome is the result of non-specific (baseline) toxicity that occurs at aqueous and whole-body concentrations that are just below lethal concentrations. Baseline toxicity is essentially a non-specific response that results from chemicals accumulating in and disturbing the function of biological membranes that leads to lethality and sublethal effects at relatively high doses. The commonality of this acute ELS toxicity syndrome among highly diverse organic and inorganic chemicals is remarkable. It is important to identify baseline toxicity because it is considered minimal toxicity that acts in all tissues and cells, and it has the potential to impair all cellular functions. This means if an effect is observed around baseline-toxic concentrations, it is likely that other cellular functions are also affected, ie, the effect is not specific. The fish ELS toxicity syndrome can also be the result of specific effects involving receptor interactions; therefore, we emphasize the importance of distinguishing between specific and non-specific toxicity responses to provide the most relevant data for environmental risk assessment.

Study on the developmental, behavioral toxicity, and toxicological mechanism of the antidepressant drug venlafaxine and its active metabolites in zebrafish.

As a representative agent of bicyclic antidepressants, venlafaxine (VEN) has become widely used worldwide and is frequently detected in surface waters with concentrations ranging from ng/L to µg/L. To evaluate the toxicological effects of such medications on aquatic species, studies on environmentally relevant concentrations are essential. Zebrafish were used as a model organism to assess growth and development in larvae and examine tissue accumulation, oxidative stress, and DNA methylation in adults. The results showed adverse effects, including an 18.5% decrease in embryo hatching rate and an increase in mortality by 18.5%. There was also a reduction in body length (4.5%) and eye area (12.2%) in the larvae, along with abnormal developmental issues, such as pericardial edema, yolk sac edema, and spinal curvature. Venlafaxine and its metabolites induced oxidative stress, leading to observable toxic effects. In adult zebrafish, VEN and O-desmethylvenlafaxine (ODV) accumulated primarily in the liver, followed by the brain and intestines, and caused a reduction in DNA methyltransferase activity, leading to DNA hypomethylation. VEN had the most significant impact on DNA methyltransferase 1 and altered its conformation more than ODV. Overall, venlafaxine was found to be more toxic than its metabolites, providing a scientific basis for evaluating the toxic effects and ecological risks of antidepressant residues on aquatic organisms.

Developmental and neurotoxic effects of dimethyl phthalate on zebrafish embryos and larvae.

Dimethyl phthalate (DMP) has been extensively utilized as a plasticizer on a global scale for many years. Its presence in the environment and its harmful effects on living organisms have raised concerns. This study aimed to examine its potential developmental neurotoxicity by utilizing zebrafish as a model. Zebrafish embryos were exposed to different concentrations of DMP (5-100 mg/L) from 4 to 120 h post-fertilization (hpf). The survival, hatching, and malformation rates were recorded for each group. Behavioral analysis was conducted on zebrafish larvae, and transgenic zebrafish Tg(elavl3:EGFP) were used to assess the impact of DMP on neuronal cells. The mRNA levels of key neurological marker genes were evaluated at 96 hpf of DMP exposure. The study revealed that exposure to DMP resulted in decreased survival and hatching rates in zebrafish. Embryos treated with 50 mg/L of DMP exhibited lower average survival rates (72.78-78.33%) between 24-96 hpf, while treatment with 25-50 mg/L of DMP resulted in reduced hatching rates (39.44% and 2.22%, respectively) at 48 hpf compared to the control group. Moreover, exposure to 25-50 mg/L of DMP caused an increase in malformations, such as tail curvature, spinal curvature, yolk sac edema and pericardial edema. Interestingly, at 24 hpf, DMP also resulted in an increase in spontaneous tail coiling in zebrafish embryos, as well as a decrease in their swimming distance at 120 hpf. Furthermore, treatment with 50 mg/L of DMP led to a decrease in the fluorescence intensity of transgenic zebrafish Tg(elavl3: EGFP). RT-qPCR analysis showed a significant down-regulation of marker genes (gap43, mbp, α1-tubulin, syn2a) associated with nervous system function in DMP-treated zebrafish. Overall, these findings offer a thorough understanding of the mechanisms underlying the neurotoxicity caused by DMP, highlighting the risk of DMP on developmental and neurotoxic effects in zebrafish. Therefore, strict supervision of DMP use and release is essential to safeguard ecological and aquatic organisms.

High-Throughput Zebrafish Screening Reveals Cardiotoxic Effects of Organophosphate Flame Retardants.

The toxicity of organophosphorus flame retardants (OPFRs) remains poorly understood, despite their widespread environmental presence and potential risks to human and ecological health. This study aimed to characterize the cardiovascular developmental toxicity of OPFRs using a high-throughput zebrafish screening model. Over thirty representative OPFRs, classified into three major groups-alkyl, aryl, and halogenated-were evaluated. Our results demonstrated that aryl-substituted OPFRs, such as triphenyl phosphate (TPHP) and tris(3,5-dimethylphenyl) phosphate (TXP), exhibit significantly more potent cardiotoxic effects compared to alkyl- and halogenated-substituted OPFRs. Specifically, heart rate of zebrafish increased by 8.3% and 11.9%, and cardiac output increased by 30.8% and 39.9% for TPHP and TXP, respectively, at a concentration of 160 μg/L. Additionally, exposure to aryl-substituted compounds like TPHP resulted in notable developmental abnormalities, including pericardial edema and skeletal bending. Molecular descriptor analysis further identified a series of essential structural features, including estrogen receptor agonist activity and bioconversion rates, which are closely linked to the observed cardiotoxicity, thus providing a mechanistic explanation for these effects. These findings offer valuable insights into the molecular mechanisms underlying OPFRs toxicity, which could inform the development of safer flame retardant alternatives. Moreover, addressing the research gaps in translating zebrafish findings to other species and real-world ecological scenarios should be further concerned.

Initial Assessment the Effects of Polyethylene Microplastics on the Growth of Zebrafish Embryos Danio rerio

The aim of this study to evaluate the effect of polyethylene (PE) microplastics to mortality rates and morphological changes of zebrafish (Danio rerio) embryos by determining the mortality ratio of embryos and changes in embryo morphological structure after 24, 48, 72 and 96 h of exposure. Zebrafish were obtained from the Faculty of Biology - Hanoi University of Science. 24-hour-old fish embryos were exposed to PE microplastic concentrations of 5; 10; 20; 50 and 100 µg/mL. The results showed that when exposed to microplastics at concentrations of 10 µg/mL or higher, only about 5-10% of mortality embryos and the ratio did not increase with increasing concentration. These embryos died in the first 24 h and the number of dead embryos did not increase throughout the experiment. A similar trend was also observed when evaluating the ratio of morphologically abnormal embryos, embryos with abnormal pericardial edema were observed throughout the experiment at the highest concentration of 100 µg/mL. The results showed the potential risk in the using plastic products for the ecological environment.

A Nanotoxicological Approach to the Effects of Metformin and Sodium Metavanadate Co-encapsulated in Polycaprolactone Nanoparticles under the Biological Parameters of Zebrafish (Danio rerio)

The present study evaluated the sublethal and lethal effects, and heart rate of Danio rerio when exposed to antidiabetic drugs, metformin (M-10), and sodium metavanadate (V-10), their association (MV-10) and the polycaprolactone nanoparticles containing poloxamer 188 with (PPMV-1, PPMV-5, and PPMV-10) or without these antidiabetics (PP-10). Acute toxicity tests were carried out to evaluate these effects. Groups V-10, MV-10, PPMV-5, PPMV-10, and PP-10 had lethal and sublethal, such as effects as pericardial edema. Concerning the heart rate, the PPMV-1, PPMV-5, PPMV-10, and PP-10 groups had a reduction compared to the other groups, indicating toxicity of the constituents of the nanoparticles. PPMV-5, PPMV-10, and PP-10 groups had sublethal and lethal effects depending on the concentration. Antidiabetics were eliminated as a possible cause and the poloxamer 188 is non-toxic at the concentrations used. In the PP-10 group, there was a dynamic of sublethal and lethal effects like the PPMV-10 group. We conclude that the presence of PCL in the formulation of nanoparticles was harmful at the cardiovascular level in embryos and eleuthero-embryos of D. rerio, affecting their development and heart rate, regardless of their concentration. Because of the results obtained, we can conclude that the toxicological evaluation of a nanomaterial is important to anticipate problems in its veterinary application since such results show possible toxicity problems.

Stranded heavy fuel oil exposure causes deformities, cardiac dysfunction, and oxidative stress in marine medaka Oryzias melastigma using an oiled-gravel-column system.

Heavy fuel oil (HFO) stranded on the coastline poses a potential threat to the health of marine fish after an oil spill. In this study, an oiled-gravel-column (OGC) system was established to investigate the toxic effects of stranded HFO on marine medaka Oryzias melastigma. HFO 380# (sulfur content 2.9%) was chosen as one type of high sulfur fuel oil for acute toxicity tests. The marine medaka larvae were exposed to the OGC system effluents with oil loading rates of 0 (control), 400, 800, 1600, and 3200µg HFO/g gravel for 144h, respectively. Results showed that a prevalence of blue sac disease signs presented teratogenic effects, including decreased circulation, ventricular stretch, cardiac hemorrhage, and pericardial edema. Moreover, the treatments (800, 1600, and 3200µg oil/g gravel) induced severe cardiotoxicity, characterized by significant bradycardia and reduced stroke volume with an overt decrease in cardiac output. Additionally, the antioxidant enzyme activities, including catalase (CAT), peroxidase (POD), and glutathione S-transferase (GST) were significantly upregulated at 800-3200µg oil/g gravel except for a marked inhibition of CAT activity at 3200µg oil/g gravel. Furthermore, significantly elevated protein carbonyl (PCO) levels were detected, suggesting that the organisms suffered severe protein oxidative damage subjected to the exposure. Overall, stranded HFO 380# exposure activated the antioxidant defense system (up-regulated POD and GST activities) of marine medaka and disrupted CAT activity, which could result in an oxidative stress state (elevated PCO levels) and might further contribute to cardiac dysfunction, deformities, and mortality.

Liquid mosquito repellent induces toxic effects in zebrafish.

Mosquitoes serve as vectors for life-threatening parasitic diseases, presenting a continuous threat throughout human history. This has resulted in the extensive utilization of various mosquito repellents, including liquid mosquito repellents (LMRs), roll-ons, and topical creams. While these products demonstrate significant efficacy, the toxicological implications associated with their use are not yet fully understood and continue to be a subject of debate. The analysis conducted using gas chromatography-mass spectrometry (GC-MS) on LMR revealed the presence of 158 distinct compounds, among which were Piperazine 2,5-dimethyl propyl and a range of hydrocarbons. The analysis of network toxicology indicated that 78 of the examined compounds contravened Lipinski's rule of five and exhibited considerable overlap with target genes associated with lung cancer pathways, thereby highlighting potential concerns regarding their carcinogenic properties. The exposure of zebrafish embryos to LMR concentrations between 0.1 and 14 µg/mL resulted in developmental toxicity assays that demonstrated a dose-dependent escalation in mortality rates and the occurrence of morphological abnormalities, such as pericardial edema and skeletal deformities. Behavioral assays demonstrated a marked decrease in locomotor activity at elevated LMR concentrations, indicating potential neurotoxic effects. Biochemical analyses revealed elevated levels of reactive oxygen species (ROS), enhanced lipid peroxidation, and diminished glutathione, which are indicative of oxidative stress. Enzyme activity assays indicated a reduction in superoxide dismutase (SOD) and catalase (CAT) activities, alongside an increase in lactate dehydrogenase (LDH) activity, which suggests the occurrence of cellular damage. Analysis of gene expression demonstrated significant dysregulation in genes associated with oxidative stress (SOD1, CAT), inflammatory markers (TNF-α, IL-1β), apoptotic regulators (p53, bcl2), and neurobiological genes (brain-derived neurotrophic factor, bdnf). The results highlight the possible health hazards linked to LMR exposure, which manifest as developmental, biochemical, and genetic alterations in zebrafish embryos.

Effects of Flurochloridone on the Developmental Toxicity in Zebrafish (Danio rerio) Embryo.

Flurochloridone (FLC) is a selective herbicide that can cause reproductive toxicity in male rats. However, limited information is available regarding the toxicity of FLC in the developmental stages of aquatic organisms. This study aimed to investigate the effects of FLC exposure during embryonic development and elucidate its potential mechanism of action. Zebrafish embryos were exposed to 6.25, 12.5, 25, and 50 μg/mL FLC for 4-144 hpf. The developmental status of embryos was recorded; the indicators of oxidative stress and embryonic apoptosis were determined. We found that FLC exposure caused severe embryonic malformations, such as pericardial edema, spinal curvature, and growth retardation, accompanied by a decreased hatching and survival rate. After exposure until 144 h postfertilization, the median lethal concentration (LC50) of FLC in zebrafish embryos was 36.9 μg/mL. Subsequently, FLC induced the accumulation of reactive oxygen species and malondialdehyde, enhanced the activity of superoxide dismutase, and activated the Keap1-Nrf2 signaling pathway. Further studies confirmed that FLC can induce apoptosis in zebrafish embryos through the activation of caspase. These results suggest that FLC induced developmental toxicity in zebrafish embryos, which provides new evidence regarding FLC toxicity in aquatic organisms and to assess human health risks.

3-Chloro-1,2-Propanediol Exposure Induces Cardiotoxicity and Behavioural Abnormalities in Zebrafish Embryos.

Numerous contemporary diseases are linked to food contamination. Pathogenic agents might stem from certain food ingredients or result from pollution stemming from food processing or packaging. One such contaminant is 3-Chloro-1,2-propanediol (3-MCPD), it has been previously reported to be produced during the preparation of chemical sauces, as well as during the heating of baked goods. Yet, uncertainty surrounds its potential to induce embryonic developmental toxicity. In this study, zebrafish were employed as the focal point to assess the impact of 3-MCPD on initial embryonic development, heart functionality, and behavior. The research unveiled that exposure of zebrafish embryos to 18, 36, and 54 mM 3-MCPD led to cardiac anomalies, including pericardial edema, reduced heart rate, and elongated SV-BA distance. Additionally, 3-MCPD exposure triggered aberrations in cardiac-related gene expression and an elevation in oxidative stress. Notably, behavioral changes were observed in 3-MCPD-exposed zebrafish embryos, while vascular development appeared unaffected. This study introduces a novel basis for comprehensive exploration of 3-MCPD toxicity.

Developmental toxicity and biochemical and biomarker in the zebrafish (Danio rerio) embryo exposed to biosynthesized cadmium oxide nanoparticles

Cadmium oxide nanoparticles (CdO-NPs) play an important role in health applications due to their antibacterial properties. However, ecotoxicological investigations of these NPs and their adverse effects on aquatic organisms are necessary to protect the environment. Zebrafish is widely used as a model organism to explore toxic effects at multiple levels of integration. Hence, the objective of this work was to pursue possible harmful impacts of CdO -NPs that have been produced through biosynthesis, utilizing extract from the lily plant Gloriosa superba leaves, on the growth and biochemical changes in zebrafish (Danio rerio) embryos and larvae. UV, SEM, TEM, FTIR, EDAX, DLS, and ZETA-potential techniques were employed to examine the structure and morphology of the biosynthesized CdO-NPs. The identification of bioactive chemicals from the leaf extract of G. superba was conducted using GC-MS. To study the in vivo toxicity of CdO-NPs, zebrafish embryos and larvae were treated with two different concentrations of G. superba leave extract (0.5 and 1.0mg/mL) at 96h after fertilization (hpf). Bended tail, pericardial edema, shortened yolk sac extension, scoliosis, and damaged eyes were observed in the CdO-NPs treated groups. In addition, there was a considerable decrease in the levels of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferases (GST), and lipid peroxidation (LPO). The CdO-NPs treated groups showed significant alterations in biochemical markers, including protein levels, glucose levels, and acetylcholinesterase (AChE) activity. Overall, our findings indicated that CdO-NPs induced a dose-dependent toxicity in zebrafish embryos. The investigated parameters serve as reliable biomarkers for the surveillance of CdO-NPs in aquatic ecosystems and their impact on living animals.

Zearalenone delays tissue regeneration by dysregulating neutrophil balance in zebrafish (Danio rerio) larvae.

Zearalenone (ZEA), a common mycotoxin, poses significant environmental and health risks. While its toxicological effects are well-studied, its impact on regeneration remains unclear. This study explored ZEA's effects on zebrafish (Danio rerio) larvae, focusing on developmental toxicity, immunotoxicity, and tissue regeneration. Embryos were exposed to 0, 0.5, 1, and 1.5μM ZEA from 6 to 72 h post-fertilization (hpf). Although hatching and survival rates remained unaffected, malformations, including body axis bending and pericardial edema, increased dose-dependently, with 4.44% abnormalities observed at 1.5μM (p=0.01). Heart rates also declined significantly at 1.5μM (75.40 vs. 72.53 beats/30s, p=0.0054). Immunotoxicity was assessed using Tg(mpx: eGFP) zebrafish to monitor neutrophil responses post-injury. ZEA exposure led to increased neutrophil counts (229.87 vs. 330.80, p<0.0001) and chemotaxis (21.15% vs. 34.57%, p<0.0001). RNA sequencing of 0 and 1.5μM groups revealed disrupted redox balance and oxygen transport, with down-regulation of hbae1, hbbe2, and hbae3 and up-regulation of hif1a, indicating hypoxia involvement. Elevated reactive oxygen species (ROS), reduced antioxidant enzyme activity, and increased apoptosis were also observed. Tail fin regeneration assays showed delayed regeneration at 1 and 1.5μM ZEA, linked to impaired immune function and oxidative stress. These findings highlight ZEA's adverse effects on developmental and regenerative processes, underscoring its environmental and health implications and the need for further research.

Assessment of the relative cardiotoxicity and behavioral effects of butylated hydroxytoluene and its metabolites in developing zebrafish (Danio rerio)

Butylated hydroxytoluene (BHT) and its transformation products are ubiquitously detected in aquatic environments. Despite studies reporting on the adverse effects of BHT exposure in early-staged zebrafish, the comparative toxicity of its metabolites is not known. To address this, zebrafish embryos were exposed continuously to 0.01–1 μM BHTs (BHT, BHT-Q, BHT-OH, BHT-CHO, and BHT-COOH) for up to 6 days. Each chemical altered the heart rates of developing zebrafish at 72 hpf. When assessing cardiac morphology at 48 and 72 hpf, BHT-COOH showed stronger effects compared to BHT in inducing pericardial edema and myocardial hypertrophy. This effect is hypothesized to be attributed to differences in transcriptional regulation of key genes during cardiac development. BHT predominantly affected transcript expression in the early (15 hpf) or late stages (48–72 hpf) of heart development, but did not impact the transcription during the middle stage (24–36 hpf). Conversely, BHT-COOH altered the expression of early transcription factors (i.e. tbx5, nkx2.5, gata4, hand2) and functional genes (i.e. myh6, nppa, cacna1ab, and atp2a2) at all stages of cardiac development. The effects on the heart may also be related to behavioral changes observed in larval fish. Behavior was most sensitive with low chemical exposures (0.01 μM), while at higher concentrations, heart rate was a more sensitive indicator of BHT-induced toxicity. Taken together, our results indicate that BHTs induce adverse effects on cardiovascular function and BHT metabolites may pose higher risk than the parent compound.

Effects of effluents from the Villa Victoria Reservoir (Mexico) on the development of Danio rerio at early life stages through apoptotic response and oxidative-induced state

As one of Mexico's most crucial water storage facilities, the Villa Victoria Reservoir (VVR) supplies water to over six million people residing in the Mexico City Metropolitan Area. In recent years, this water resource has been subjected to significant risks due to several factors, including human population growth, alterations in global climate patterns, excessive resource utilization, and insufficient protective regulations, thereby endangering not only the biocenosis itself, but also the water supply for numerous inhabitants. This study aimed to evaluate the current state of the reservoir through the determination of conventional and emerging pollutants present in the sampling points, as well as embryotoxicity and oxidative damage in Danio rerio embryos exposed to effluents from the VVR. Embryotoxicity was quantified using the General Morphology Score (GMS) and teratogenic index, whereas oxidative damage was assessed based on lipid peroxidation, hydroperoxide content, oxidized proteins, antioxidant enzyme activity, and gene expression. These results revealed the presence of heavy metals, diverse pharmaceutical compounds, and pesticides. In addition, elevated lipid, hydroperoxide, and protein oxidation accompanied by alterations in superoxide dismutase (SOD) and catalase (CAT) enzymatic activity were observed during exposure. GMS resulted in impaired embryo development and teratogenic effects, including pericardial, axial, and skeletal edema. Furthermore, the upregulation of genes associated with apoptotic processes and antioxidant defense reflects a comprehensive response to oxidative stress. The study concluded that pollutants in VVR water induced oxidative damage, modified antioxidant activity, elicited embryotoxicity, and upregulated oxidative damage-related genes. The findings underscore the necessity of undertaking restoration efforts for water sources, as pollution can potentially endanger aquatic organisms and human well-being.