Zirconia oxide nanoparticles (ZrO
2
NPs) are known to be one of the neutral bioceramic metal compounds that has been widely used for their beneficial applications in many biomedical areas, in dental ...implants, bone joint replacements, drug delivery vehicles, and in various industrial applications. To study the effects of ZrO
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NPs on zebrafish model, we used early life stages of the zebrafish (Danio rerio) to examine such effects on embryonic development in this species. ZrO
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NPs were synthesized by the sol-gel method, size about 15-20 nm and characterized by SEM, EDX, XRD, FTIR, UV-Vis Spectra. In this study, zebrafish embryos were treated with ZrO
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NPs 0.5, 1, 2, 3, 4, or 5 μg of nanoparticles/ml during 24-96 hour post fertilization (hpf). The results showed that ≥0.5-1 μg/ml of ZrO
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NPs instigated developmental acute toxicity in these embryos, causing mortality, hatching delay, and malformation. ZrO
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NPs exposure induced axis bent, tail bent, spinal cord curvature, yolk-sac, and pericardial edema. A typical phenotype was observed as an unhatched dead embryo at ≥1 μg/ml of ZrO
2
NPs exposure. This study is one of the first reports on developmental toxicity of zebrafish embryos caused by zirconium oxide nanoparticles in aquatic environments. Our results show that exposure of zirconium oxide nanoparticles is more toxic to embryonic zebrafish at lower concentrations. The results will contribute to the current understanding of the potential biomedical toxicological effects of nanoparticles and support the safety evaluation and synthesis of Zirconia oxide nanoparticles.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Isoliquiritigenin (ISL) is an emerging natural flavonoid found in the roots of licorice, exhibits antioxidant, anti-cancer, anti-inflammatory, anti-allergic, cardioprotective, hepatoprotective and ...neuroprotective properties. However, the effect of ISL in embryonic development is yet to be elucidated, and the mechanisms underlying its target-organ toxicity and harmful side effects are still unclear. In the present study, we employed zebrafish embryos to study the developmental toxicity effect of ISL and its underlying mechanisms. Zebrafish embryos upon treatment with either vehicle control (0.1% DMSO) or ISL solutions for 4–96 h post fertilization (hpf) showed that ISL exposure instigated severe developmental toxicity in heart, liver, and nervous system. Mortality and morphological abnormalities were also observed. High concentrations of ISL exposure resulted in abnormal phenotypes and embryonic malformations including pericardial edema, swim bladder defects, yolk retention, curved body shape and shortening of body length. Moreover, ISL exposure led to significant loss of dopaminergic neurons accompanied by reduced locomotor behaviour. Apoptotic cells were predominantly located in the heart area of 96 hpf embryo. Additionally, ISL significantly increased the levels of reactive oxygen species, lipid peroxidation content and decreased antioxidant enzyme activities. The expressions pattern of apoptosis-related genes Bad, Cyto c, Caspase-9, Caspase-3 and Bax/Bcl-2 indicated that the oxidative stress–induced apoptosis triggered by ISL suggest involvement of Nrf2-HO1/JNK-ERK/mitochondrion pathways. In conclusion, here we provide first evidence that demonstrate ISL-induced dose-dependent developmental toxicity in zebrafish embryos. Furthermore, gene expression patterns in the embryos correlate the above and reveal potential genetic mechanisms of developmental toxicity.
•ISL triggered developmental toxicity in zebrafish, caused death and malformations.•ISL exposure instigated developmental toxicity in heart, liver, and nervous system.•ISL triggered apoptosis in zebrafish via Nrf2-HO1/JNK-ERK/mitochondrion pathway.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•PM10 induced neurodevelopmental toxicity in zebrafish embryos and larvae.•PM10 exposure inhibited the locomotor behavior and growth of dopaminergic neurons.•PM10 exposure induced the ...neurovasculature defects and cerebral haemorrhage.•PM10 altered the expression of genes associated with embryonic brain development including those of dopaminergic pathway.
Particulate matter with 10 μm or less in diameter (PM10) exposure is a major threat to health and environment around the world. Even though a number of clinical and experimental studies have focused on the cardiopulmonary effects of PM10, its impact on neurovascular development and the underlying toxicity is relatively less studied. The present study is therefore undertaken to evaluate the potential toxic effects of PM10 on neurodevelopment and the associated gene expression profiles in the zebrafish embryo/larvae. During 2017–2018, PM10 samples (24 h sampling, 180 sampling days) were collected in an urban downtown site of Jinan, Shandong province, China. To delineate the potential toxic effects of PM10 during neurodevelopment, zebrafish embryos/larvae were exposed to different concentrations viz., 25, 50, 100, 200, and 400 μg/mL of PM10 solution for 24–120 h post-fertilization (hpf) and the effects on the mortality, morphology, swimming behavior, electroencephalogram discharges, growth of dopaminergic neurons, neurovasculature development and gene expression profiles of dopaminergic and neurodevelopment-related genes using qRT-PCR were studied.
A significant increase in the mortality rate and morphological abnormalities were observed in 200 μg/mL of the PM10 treated group at 120 hpf. High concentrations (≥100 μg/mL) of PM10 exposure reduced locomotor behavior, caused abnormal electroencephalogram discharges, degeneration of dopaminergic neurons, inhibition of neurovascular development, cerebral hemorrhage, and significant changes in the expression pattern of genes involved in dopaminergic pathway and neurodevelopment such as (th1, dat, drd1, drd2a, drd3, drd4b, syn2a, gap43, α1-tubulin, gfap, map2, elavl3, eno2, neurog1, sox2, shha, and mbp). Taken together, all these parameters collectively imply developmental neurotoxicity and dysfunction of the dopaminergic neurons which provides the first evidence of PM10-induced neurodevelopmental toxicity in the zebrafish embryo/larvae.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Traditional Chinese medicine (TCM) is used in the treatment of Parkinson’s disease (PD) worldwide. Tongtian Oral Liquid (TTKFY) is one such patented TCM, and a poly-herbal formulation, composed of 11 ...herbal constituents, which possess neuroprotective, antioxidant, pain-relieving properties. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP), a neurotoxicant is used to induce PD in animal models. The present study was aimed to evaluate the neuroprotective effects of TTKFY, on dopaminergic neuron development, antioxidant activities, and gene expression involved in the dopaminergic pathway in the MPTP-treated zebrafish model. Zebrafish larvae were treated with MPTP (70 μM) to induce PD and then by different concentrations (0.5, 1, 2, 4 ml/L) of TTKFY. Transgenic zebrafish Vmat: GFP at 5 dpf were used to observe the development of dopaminergic neurons. The activities of T-Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malonaldehyde (MDA) and mRNA gene expression of dopamine pathway were quantified. MPTP-treated zebrafish larvae showed degeneration of dopaminergic neurons, locomotion dysfunction, diminished activities of antioxidant enzymes, MDA accumulation, and altered gene expression of dopamine pathway. In contrast, TTKFY protected dopaminergic neurons, ameliorated behavioral impairments, antioxidant activities and mRNA gene expression of dopamine pathway in a dose-dependent manner. Thus, TTKFY confers protective effects against MPTP-induced neurotoxicity and the mechanisms of protection may be related to the recovery of dopaminergic neurons by reducing oxidative stress via restoring cellular defense mechanisms and thereby highlighting its therapeutic potential to prevent the progression of PD. Further studies are necessary to elucidate the mechanism of action of TTKFY on neuroprotection in the MPTP-induced PD model.
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•MPTP is a neurotoxicant used to induce Parkinson disease (PD) in animal models.•Tongtian oral liquid (TTKFY), a Chinese herbal medicine is composed of 11 herbal constituents.•TTKFY restored the dopaminergic loss, and locomotory defects caused by MPTP.•TTKFY restored the antioxidant activities and the mRNA expression of genes related to dopaminergic pathway.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Obesity is a complex, multifactorial disorder influenced by the interaction of genetic, epigenetic, and environmental factors. Obesity increases the risk of contracting many chronic diseases or ...metabolic syndrome. Researchers have established several mammalian models of obesity to study its underlying mechanism. However, a lower vertebrate model for conveniently performing drug screening against obesity remains elusive. The specific aim of this study was to create a zebrafish obesity model by over expressing the insulin signaling hub of the Akt1 gene.
Skin oncogenic transformation screening shows that a stable zebrafish transgenic of Tg(krt4Hsa.myrAkt1)(cy18) displays severely obese phenotypes at the adult stage. In Tg(krt4:Hsa.myrAkt1)(cy18), the expression of exogenous human constitutively active Akt1 (myrAkt1) can activate endogenous downstream targets of mTOR, GSK-3α/β, and 70S6K. During the embryonic to larval transitory phase, the specific over expression of myrAkt1 in skin can promote hypertrophic and hyperplastic growth. From 21 hour post-fertilization (hpf) onwards, myrAkt1 transgene was ectopically expressed in several mesenchymal derived tissues. This may be the result of the integration position effect. Tg(krt4:Hsa.myrAkt1)(cy18) caused a rapid increase of body weight, hyperplastic growth of adipocytes, abnormal accumulation of fat tissues, and blood glucose intolerance at the adult stage. Real-time RT-PCR analysis showed the majority of key genes on regulating adipogenesis, adipocytokine, and inflammation are highly upregulated in Tg(krt4:Hsa.myrAkt1)(cy18). In contrast, the myogenesis- and skeletogenesis-related gene transcripts are significantly downregulated in Tg(krt4:Hsa.myrAkt1)(cy18), suggesting that excess adipocyte differentiation occurs at the expense of other mesenchymal derived tissues.
Collectively, the findings of this study provide direct evidence that Akt1 signaling plays an important role in balancing normal levels of fat tissue in vivo. The obese zebrafish examined in this study could be a new powerful model to screen novel drugs for the treatment of human obesity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Airborne total suspended particles (TSP) and particulate matter (PM2.5) threaten global health and their potential impact on cardiovascular and respiratory diseases are extensively studied. Recent ...studies attest premature deaths, low birth weight, and congenital anomalies in the fetus of pregnant women exposed to air pollution. In this regard, only few studies have explored the effects of TSP and PM2.5 on cardiovascular and cerebrovascular development. As both TSP and PM2.5 differ in size and composition, this study is attempted to assess the variability in toxicity effects between TSP and PM2.5 on the development of cardiovascular and cerebrovascular systems and the underlying mechanisms in a zebrafish model. To explore the potential toxic effects of TSP and PM2.5, zebrafish embryos/larvae were exposed to 25, 50, 100, 200, and 400 μg/ml of TSP and PM2.5 from 24 to 120 hpf (hours post‐fertilization). Both TSP and PM2.5 exposure increased the rate of mortality, malformations, and oxidative stress, whereas locomotor behavior, heart rate, blood flow velocity, development of cardiovasculature and neurovasculature, and dopaminergic neurons were reduced. The expression of genes involved in endoplasmic reticulum stress (ERS), Wnt signaling, and central nervous system (CNS) development were altered in a dose‐ and time‐dependent manner. This study provides evidence for acute exposure to TSP and PM2.5‐induced cardiovascular and neurodevelopmental toxicity, attributed to enhanced oxidative stress and aberrant gene expression. Comparatively, the effects of PM2.5 were more pronounced than TSP.
Airborne TSP and PM2.5 pollution are considered as a major global threat to public health as they contribute a combination of toxic compounds. In the present study, in a zebra fish model, TSP and PM2.5 exposure increased mortality, malformations, delayed hatchability, ROS production, impaired the growth of blood vessels, heart rate, blood flow velocity, development of DA (dopamine) neurons, and locomotor behavior. PM2.5 exposure alone affected neurovasculature‐induced cerebral hemorrhage. Both altered the gene expression profiles associated with cardiovascular and brain development.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The aim of this investigation is to optimize the process parameters to obtain minimum corrosion rate and weight loss of Al/SiCp metal matrix composites. A Taguchi based grey relation analysis was ...carried out. The process parameters such as number of hours dipped in 3% NaCl solution, vol.% of SiCp and aging at 170°C for hours were considered. The working range of each process parameters were fixed based on minimum weight loss and low corrosion rate. The test was carried out using Taguchi based grey relationship analysis. Three factor three level L9 orthogonal array was used and output responses such as weight loss and corrosion rate were calculated. Based on the grey relationship analysis, the rank of each process parameters was calculated. Based on the F value, the vol. % of SiCp (38.42%) on the metal matrix composite followed by number of hours samples immersed in 3% NaCl solution (35.3%) and aging at 170°C for hours (25.78%) were found as influencing parameters on corrosion rate and weight loss. The surface of corroded samples was investigated and reported.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Rapid excited-state quenching in the solid state is a widespread limitation for organic chromophores. Even when molecules are dispersed in neutral host matrices, photoluminescence quantum yields ...decrease sharply with increased concentration, pointing to efficient intermolecular non-radiative decay pathways that remain poorly understood. Here we study the nature of the intermolecular states formed in dispersions of the prototypical BODIPY dyes. Using temperature-dependent and time-resolved photoluminescence measurements, we describe the processes of energy transfer into excimer states and, in materials with suitable chemical structure, excitonically coupled dimers. These dimer states exhibit remarkable near-unity quantum yield.
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