An approach to evaluating the potential teratogenic and neurotoxic mechanism of BHA based on apoptosis induced by oxidative stress in zebrafish embryo (Danio rerio)

2020 ◽  
pp. 096032712095214
Author(s):  
A Baran ◽  
S Yildirim ◽  
A Ghosigharehaghaji ◽  
İ Bolat ◽  
E Sulukan ◽  
...  
Keyword(s):  
Oxidative Dna Damage ◽  
Cellular Level ◽  
Whole Body ◽  
Hatching Rate ◽  
Hydroxyl Groups ◽  
Zebrafish Embryos ◽  
Dependent Manner ◽  
Zebrafish Larvae ◽  
Induced Apoptosis ◽  
The Brain

Butylated hydroxyanisole (BHA) has been widely used in the cosmetics, pharmaceutical, and food industries due to its antioxidant activity. Despite the antioxidant effects, reported adverse effects of BHA at the cellular level have made its use controversial. In this regard, this study was performed to elucidate the potential toxicity mechanism caused by BHA at the molecular level in zebrafish embryos. For this purpose, zebrafish embryos were exposed to BHA at levels of 0.5, 1, 5, 7.5 and 10 ppm and monitored at 24, 48, 72 and 96 hours. Survival rate, hatching rate and malformations were evaluated. We examined the potential for reactive oxygen species (ROS) production and apoptosis signalling accumulation in the whole body. Moreover, we evaluated histopathological and immunohistochemical (8-OHDG) characterization of the brain in zebrafish embryos at the 96th hour. We also examined apoptosis, histopathological and immunohistochemical (8-OHDG) characteristics in 96 hpf zebrafish larvae exposed to tertiary butylhydroquinone (TBHQ), one of the major metabolites of BHA, at doses of 0.5, 2.5, 3.75 and 5 ppm. Consequently, it has been considered that increased embryonic and larval malformations in this study may have been caused by ROS-induced apoptosis. After 96 h of exposure, positive 8-OHdG immunofluorescence, degenerative changes, and necrosis were observed in the brain of BHA and TBHQ-treated zebrafish larvae in a dose-dependent manner. BHA and TBHQ exposure could lead to an increase in 8-OHdG activities by resulting oxidative DNA damage. In particular, the obtained data indicate that the induction of ROS formation, occurring during exposure to BHA and/or multiple hydroxyl groups, could be responsible for apoptosis.

scholarly journals Study of the Potential Hepatoprotective Effect of Myo-Inositol and Its Influence on Zebrafish Development

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3346
Author(s):  
Tomasz Antonowski ◽  
Karol Wiśniewski ◽  
Piotr Podlasz ◽  
Adam Osowski ◽  
Joanna Wojtkiewicz
Keyword(s):  
Hepatoprotective Effect ◽  
Control Group ◽  
Hatching Rate ◽  
Zebrafish Embryos ◽  
Low Doses ◽  
Zebrafish Development ◽  
Natural Substance ◽  
Zebrafish Larvae ◽  
Negative Effect ◽  
High Doses

Inositol is a natural substance found widely in plants. It is used in therapies for many medical cases. The aim of this study was to determine the toxicity of myo-inositol (MI) and to investigate its potential hepatoprotective character. In the first part of the study, zebrafish embryos were incubated with 5, 10, 20, 40, 60, 80, and 100 mg/mL MI. Endpoints such as survivability, hatching rate, malformation, and mobility were evaluated. Our results demonstrated that the high doses of MI lead to increased mortality and malformations and reduce the hatching rate in comparison to the control group. Moreover, low doses of this compound do not produce a negative effect on zebrafish and even have the ability to increase the hatchingrate and mobility. In the second part of the study, the hepatoprotective effect of MI was tested. Zebrafish larvae from the line Tg(fabp10a:DsRed) were incubated for 24 h with 1% and 2% ethanol (EtOH),5 mg/mL of MI with 1% EtOH, and 5 mg/mL of MI with 2% EtOH. No significant differences between the groups with EtOH and the group treated with EtOH with MI were observed. Our results suggest that MI has no positive benefits on hepatocytes of zebrafish larvae.

scholarly journals Differential Modulation of the Central and Peripheral Monoaminergic Neurochemicals by Deprenyl in Zebrafish Larvae

Toxics ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 116
Author(s):  
Marina Bellot ◽  
Helena Bartolomé ◽  
Melissa Faria ◽  
Cristian Gómez-Canela ◽  
Demetrio Raldúa
Keyword(s):  
Homovanillic Acid ◽  
Whole Body ◽  
Control Group ◽  
Monoamine Oxidase B ◽  
Differential Modulation ◽  
Behavioral Impairment ◽  
Translational Neuroscience ◽  
Zebrafish Larvae ◽  
Neuroscience Research ◽  
The Brain

Zebrafish embryos and larvae are vertebrate models increasingly used in translational neuroscience research. Behavioral impairment induced by the exposure to neuroactive or neurotoxic compounds is commonly linked to changes in modulatory neurotransmitters in the brain. Although different analytical methods for determining monoaminergic neurochemicals in zebrafish larvae have been developed, these methods have been used only on whole larvae, as the dissection of the brain of hundreds of larvae is not feasible. This raises a key question: Are the changes in the monoaminergic profile of the whole larvae predictive of the changes in the brain? In this study, the levels of ten monoaminergic neurotransmitters were determined in the head, trunk, and the whole body of zebrafish larvae in a control group and in those treated for 24 h with 5 M deprenyl, a prototypic monoamine-oxidase B inhibitor, eight days post-fertilization. In control larvae, most of the monoaminergic neurochemicals were found at higher levels in the head than in the trunk. Significant changes were found in the distribution of some neurochemicals after deprenyl-treatment, with serotonin and norepinephrine increasing in both the head and the trunk, whereas dopamine, L-DOPA, and homovanillic acid levels were only modulated in the head. In fact, the highly significant increase in dopamine levels observed in the head after deprenyl-treatment was not detected in the whole-body analysis. These results indicate that the analysis of neurotransmitters in the zebrafish larvae whole-body should not be used as a general surrogate of the brain.

scholarly journals Effect of Water-Pipe Smoking on the Normal Development of Zebrafish

2021 ◽  
Vol 18 (21) ◽  
pp. 11659
Author(s):  
Zain Zaki Zakaria ◽  
Shaima Ahmad Aladwi ◽  
Fatiha Benslimane ◽  
Enas S. Al-Absi ◽  
Mashael Al-Shafai ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Normal Development ◽  
Human Life ◽  
Expression Patterns ◽  
Tobacco Consumption ◽  
Cardiac Biomarkers ◽  
Zebrafish Embryos ◽  
Dependent Manner ◽  
Water Pipe ◽  
Induced Apoptosis

Background: Among all types of tobacco consumption, Water-Pipe Smoking (WPS) is the most widely used in the Middle East and second-most in several other countries. The effect of WPS on normal development is not yet fully understood, thus the aim of this study is to explore the acute toxicity effects of WPS extract on zebrafish larvae. Methods: In this study, we compared the effects of WPS smoke condensates at concentrations varying from 50 to 200 µg/mL on developmental, cardiac, and behavioural (neurotoxicity) functions. Gene expression patterns of cardiac biomarkers were also evaluated by RT-qPCR. Results: Exposing zebrafish embryos to 50, 100, 150 and 200 µg/mL WPS for three days did not affect the normal morphology of Zebrafish embryos, as the tail flicking, behavioural and locomotion assays did not show any change. However, WPS deregulated cardiac markers including atrial natriuretic peptide (ANP/NPPA) and brain natriuretic peptide (BNP/NPPB). Furthermore, it induced apoptosis in a dose-dependent manner. Conclusion: Our data demonstrate that WPS can significantly affect specific cardiac parameters during the normal development of zebrafish. Further investigations are necessary to elucidate the pathogenic outcome of WPS on different aspects of human life, including pregnancy.

scholarly journals Comparative Toxicity Assessment of Kratom Decoction, Mitragynine and Speciociliatine Versus Morphine on Zebrafish (Danio rerio) Embryos

2021 ◽  
Vol 12 ◽  
Author(s):  
Thenmoly Damodaran ◽  
Nelson Jeng-Yeou Chear ◽  
Vikneswaran Murugaiyah ◽  
Mohd Nizam Mordi ◽  
Surash Ramanathan
Keyword(s):  
Therapeutic Potential ◽  
Developmental Toxicity ◽  
Toxicity Assessment ◽  
Spinal Curvature ◽  
Hatching Rate ◽  
Morphological Development ◽  
Zebrafish Embryos ◽  
Dependent Manner ◽  
Zebrafish Model ◽  
Concentration Dependent Manner

Background: Kratom (Mitragyna speciosa Korth), a popular opioid-like plant holds its therapeutic potential in pain management and opioid dependence. However, there are growing concerns about the safety or potential toxicity risk of kratom after prolonged use.Aim of the study: The study aimed to assess the possible toxic effects of kratom decoction and its major alkaloids, mitragynine, and speciociliatine in comparison to morphine in an embryonic zebrafish model.Methods: The zebrafish embryos were exposed to kratom decoction (1,000–62.5 μg/ml), mitragynine, speciociliatine, and morphine (100–3.125 μg/ml) for 96 h post-fertilization (hpf). The toxicity parameters, namely mortality, hatching rate, heart rate, and morphological malformations were examined at 24, 48, 72, and 96 hpf, respectively.Results: Kratom decoction at a concentration range of ≥500 μg/ml caused 100% mortality of zebrafish embryos and decreased the hatching rate in a concentration-dependent manner. Meanwhile, mitragynine and speciociliatine exposure resulted in 100% mortality of zebrafish embryos at 100 μg/ml. Both alkaloids caused significant alterations in the morphological development of zebrafish embryos including hatching inhibition and spinal curvature (scoliosis) at the highest concentration. While exposure to morphine induced significant morphological malformations such as pericardial oedema, spinal curvature (lordosis), and yolk edema in zebrafish embryos.Conclusion: Our findings provide evidence for embryonic developmental toxicity of kratom decoction and its alkaloids both mitragynine and speciociliatine at the highest concentration, hence suggesting that kratom consumption may have potential teratogenicity risk during pregnancy and thereby warrants further investigations.

Poly-L-arginine: Enhancing Cytotoxicity and Cellular Uptake of Doxorubicin and Necrotic Cell Death

2019 ◽  
Vol 18 (10) ◽  
pp. 1448-1456 ◽  
Author(s):  
Bahareh Movafegh ◽  
Razieh Jalal ◽  
Zobeideh Mohammadi ◽  
Seyyede A. Aldaghi
Keyword(s):  
Cell Death ◽  
Cellular Uptake ◽  
Combined Treatment ◽  
Annexin V ◽  
Cell Penetrating Peptides ◽  
Short Exposure ◽  
Dependent Manner ◽  
Du145 Cells ◽  
Induced Apoptosis ◽  
Resistance To Doxorubicin

Objective: Cell resistance to doxorubicin and its toxicity to healthy tissue reduce its efficiency. The use of cell-penetrating peptides as drug delivery system along with doxorubicin is a strategy to reduce its side effects. In this study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are assessed. Methods: The cytotoxicity of doxorubicin and poly-L-arginine, alone and in combination, in DU145 cells was evaluated at different exposure times using MTT assay. The influence of poly-L-arginine on doxorubicin delivery into cells was evaluated by fluorescence microscopy and ultraviolet spectroscopy. DAPI and ethidium bromide- acridine orange stainings, flow cytometry using annexin V/propidium iodide, western blot analysis with anti-p21 antibody and caspase-3 activity were used to examine the influence of poly-L-arginine on doxorubicininduced cell death. Results: Poly-L-arginine had no cytotoxicity at low concentrations and short exposure times. Poly-L-arginine increased the cytotoxic effect of doxorubicin in DU145 cells in a time-dependent manner. But no significant reduction was found in HFF cell viability. Poly-L-arginine seems to facilitate doxorubicin uptake and increase its intracellular concentration. 24h combined treatment of cells with doxorubicin (0.5 µM) and poly-L-arginine (1 µg ml-1) caused a small increase in doxorubicin-induced apoptosis and significantly elevated necrosis in DU145 cells as compared to each agent alone. Conclusion: Our results indicate that poly-L-arginine at lowest and highest concentrations act as proliferationinducing and antiproliferative agents, respectively. Between these concentrations, poly-L-arginine increases the cellular uptake of doxorubicin and its cytotoxicity through induction of necrosis.

VDAC1 Mediated Anticancer Activity of Gallic Acid in Human Lung Adenocarcinoma A549 Cells

2018 ◽  
Vol 18 (2) ◽  
pp. 255-262 ◽  
Author(s):  
Aikebaier Maimaiti ◽  
Amier Aili ◽  
Hureshitanmu Kuerban ◽  
Xuejun Li
Keyword(s):  
Western Blot ◽  
Cell Viability ◽  
Gallic Acid ◽  
Molecular Mechanisms ◽  
A549 Cells ◽  
Dependent Manner ◽  
Lung Carcinoma Cells ◽  
Induced Apoptosis ◽  
The Impact

Aims: Gallic acid (GA) is generally distributed in a variety of plants and foods, and possesses cell growth-inhibiting activities in cancer cell lines. In the present study, the impact of GA on cell viability, apoptosis induction and possible molecular mechanisms in cultured A549 lung carcinoma cells was investigated. Methods: In vitro experiments showed that treating A549 cells with various concentrations of GA inhibited cell viability and induced apoptosis in a dose-dependent manner. In order to understand the mechanism by which GA inhibits cell viability, comparative proteomic analysis was applied. The changed proteins were identified by Western blot and siRNA methods. Results: Two-dimensional electrophoresis revealed changes that occurred to the cells when treated with or without GA. Four up-regulated protein spots were clearly identified as malate dehydrogenase (MDH), voltagedependent, anion-selective channel protein 1(VDAC1), calreticulin (CRT) and brain acid soluble protein 1(BASP1). VDAC1 in A549 cells was reconfirmed by western blot. Transfection with VDAC1 siRNA significantly increased cell viability after the treatment of GA. Further investigation showed that GA down regulated PI3K/Akt signaling pathways. These data strongly suggest that up-regulation of VDAC1 by GA may play an important role in GA-induced, inhibitory effects on A549 cell viability.

Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brain stems in vitro

2001 ◽  
Vol 91 (6) ◽  
pp. 2703-2712 ◽  
Author(s):  
Stephen M. Johnson ◽  
Julia E. R. Wilkerson ◽  
Daniel R. Henderson ◽  
Michael R. Wenninger ◽  
Gordon S. Mitchell
Keyword(s):  
Brain Stem ◽  
Respiratory Activity ◽  
Dependent Manner ◽  
Frequency Increase ◽  
Burst Frequency ◽  
Bath Application ◽  
Burst Amplitude ◽  
Dose Dependent ◽  
The Brain

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly decreased integrated burst amplitude by ∼45% ( P < 0.05); burst frequency decreased in a dose-dependent manner with 20 μM abolishing bursts in 9 of 13 preparations ( P < 0.05). These 5-HT-dependent effects were mimicked by application of a 5-HT1A agonist, but not a 5-HT1B agonist, and were abolished by the broad-spectrum 5-HT antagonist, methiothepin. During 5-HT (20 μM) washout, frequency rebounded to levels above the original baseline for 40 min ( P < 0.05) and remained above baseline for 2 h. A 5-HT3 antagonist (tropesitron) blocked the post-5-HT rebound and persistent frequency increase. A 5-HT3 agonist (phenylbiguanide) increased frequency during and after bath application ( P < 0.05). When phenylbiguanide was applied to the brain stem of brain stem/spinal cord preparations, there was a persistent frequency increase ( P < 0.05), but neither spinal-expiratory nor -inspiratory burst amplitude were altered. The 5-HT3receptor-dependent persistent frequency increase represents a unique model of plasticity in vertebrate rhythm generation.

Thymoquinone sensitizes human hepatocarcinoma cells to TRAIL-induced apoptosis via oxidative DNA damage

DNA Repair ◽  
2021 ◽  
pp. 103117
Author(s):  
Ruikui Zhang ◽  
Tao Wu ◽  
Peipei Zheng ◽  
Ming Liu ◽  
Guixiang Xu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Hepatocarcinoma Cells ◽  
Induced Apoptosis ◽  
Human Hepatocarcinoma Cells

scholarly journals The Effect of Hispidulin, a Flavonoid from Salvia plebeia, on Human Nasopharyngeal Carcinoma CNE-2Z Cell Proliferation, Migration, Invasion, and Apoptosis

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1604
Author(s):  
Yiqun Dai ◽  
Xiaolong Sun ◽  
Bohan Li ◽  
Hui Ma ◽  
Pingping Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Nasopharyngeal Carcinoma ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Etoh Extract ◽  
Tumor Drug Resistance ◽  
Diphenyltetrazolium Bromide ◽  
Scratch Wound ◽  
Low Toxicity ◽  
Induced Apoptosis

Nasopharyngeal carcinoma (NPC) is a common malignant head and neck tumor. Drug resistance and distant metastasis are the predominant cause of treatment failure in NPC patients. Hispidulin is a flavonoid extracted from the bioassay-guided separation of the EtOH extract of Salvia plebeia with strong anti-proliferative activity in nasopharyngeal carcinoma cells (CNE-2Z). In this study, the effects of hispidulin on proliferation, invasion, migration, and apoptosis were investigated in CNE-2Z cells. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and the colony formation assay revealed that hispidulin could inhibit CNE-2Z cell proliferation. Hispidulin (25, 50, 100 μM) also induced apoptosis in a dose-dependent manner in CNE-2Z cells. The expression of Akt was reduced, and the expression of the ratio of Bax/Bcl-2 was increased. In addition, scratch wound and transwell assays proved that hispidulin (6.25, 12.5, 25 μM) could inhibited the migration and invasion in CNE-2Z cells. The expressions of HIF-1α, MMP-9, and MMP-2 were decreased, while the MMPs inhibitor TIMP1 was enhanced by hispidulin. Moreover, hispidulin exhibited potent suppression tumor growth and low toxicity in CNE-2Z cancer-bearing mice at a dosage of 20 mg/kg/day. Thus, hispidulin appears to be a potentially effective agent for NPC treatment.

scholarly journals UV-induced neuronal degeneration in the rat cerebral cortex

2021 ◽  
Author(s):  
Mariko Nakata ◽  
Masayuki Shimoda ◽  
Shinya Yamamoto
Keyword(s):  
Uv Irradiation ◽  
Neuronal Degeneration ◽  
Uv Light ◽  
Brain Lesion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
Focal Brain Injury ◽  
The Brain ◽  
And Oxidative Stress

Abstract Irradiation with ultraviolet (UV) light on the cortical surface can induce a focal brain lesion (UV lesion) in rodents. In the present study, we investigated the process of establishing a UV lesion. Rats underwent UV irradiation (365 nm wavelength, 2.0 mWh) over the dura, and time-dependent changes in the cortical tissue were analyzed histologically. We found that the majority of neurons in the lesion started to degenerate within 24 hours and the rest disappeared within 5 days after irradiation. UV-induced neuronal degeneration progressed in a layer-dependent manner. Moreover, UV-induced terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity and heme oxygenase-1 (HO-1) immunoreactivity were also detected. These findings suggest that UV irradiation in the brain can induce gradual neural degeneration and oxidative stress. Importantly, UV vulnerability may vary among cortical layers. UV-induced cell death may be due to apoptosis; however, there remains a possibility that UV-irradiated cells were degenerated via processes other than apoptosis. The UV lesion technique will not only assist in investigating brain function at a targeted site but may also serve as a pathophysiological model of focal brain injury and/or neurodegenerative disorders.

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