• Title/Summary/Keyword: zebrafish toxicity

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Effects of the Particulate Matter2.5 (PM2.5) on Lipoprotein Metabolism, Uptake and Degradation, and Embryo Toxicity

  • Kim, Jae-Yong;Lee, Eun-Young;Choi, Inho;Kim, Jihoe;Cho, Kyung-Hyun
    • Molecules and Cells
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    • 제38권12호
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    • pp.1096-1104
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    • 2015
  • Particulate $matter_{2.5}$ ($PM_{2.5}$) is notorious for its strong toxic effects on the cardiovascular, skin, nervous, and reproduction systems. However, the molecular mechanism by which $PM_{2.5}$ aggravates disease progression is poorly understood, especially in a water-soluble state. In the current study, we investigated the putative physiological effects of aqueous $PM_{2.5}$ solution on lipoprotein metabolism. Collected $PM_{2.5}$ from Seoul, Korea was dissolved in water, and the water extract (final 3 and 30 ppm) was treated to human serum lipoproteins, macrophages, and dermal cells. $PM_{2.5}$ extract resulted in degradation and aggregation of high-density lipoprotein (HDL) as well as low-density lipoprotein (LDL); apoA-I in HDL aggregated and apo-B in LDL disappeared. $PM_{2.5}$ treatment (final 30 ppm) also induced cellular uptake of oxidized LDL (oxLDL) into macrophages, especially in the presence of fructose (final 50 mM). Uptake of oxLDL along with production of reactive oxygen species was accelerated by $PM_{2.5}$ solution in a dose-dependent manner. Further, $PM_{2.5}$ solution caused cellular senescence in human dermal fibroblast cells. Microinjection of $PM_{2.5}$ solution into zebrafish embryos induced severe mortality accompanied by impairment of skeletal development. In conclusion, water extract of $PM_{2.5}$ induced oxidative stress as a precursor to cardiovascular toxicity, skin cell senescence, and embryonic toxicity via aggregation and proteolytic degradation of serum lipoproteins.

Evaluation on Anticancer Effect Against HL-60 Cells and Toxicity in vitro and in vivo of the Phenethyl Acetate Isolated from a Marine Bacterium Streptomyces griseus

  • Lee, Ji-Hyeok;Zhang, Chao;Ko, Ju-Young;Lee, Jung-Suck;Jeon, You-Jin
    • Fisheries and Aquatic Sciences
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    • 제18권1호
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    • pp.35-44
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    • 2015
  • We previously identified Streptomyces griseus as an anti-cancer agent (Kim et al., 2014). In this study, we isolated compounds from S. griseus and evaluated their anticancer effect and toxicity in vitro and in vivo. Preparative centrifugal partition chromatography (CPC) was used to obtain three compounds, cyclo($_{\small{L}}$-[4-hydroxyprolinyl]-$_{\small{L}}$-leucine], cyclo($_{\small{L}}$-Phe-trans-4-hydroxy-$_{\small{L}}$-Pro) and phenethyl acetate (PA). We chose PA, which had the highest anticancer activity, as a target compound for further experiments. PA induced the formation of apoptotic bodies, DNA fragmentation, DNA accumulation in $G_0/G_1$ phase, and reactive oxygen species (ROS) formation. Furthermore, PA treatment increased Bax/Bcl-xL expression, activated caspase-3, and cleaved poly-ADP-ribose polymerase (PARP) in HL-60 cells. Simultaneous evaluation in vitro and in vivo, revealed that PA exhibited no toxicity in Vero cells and zebrafish embryos. We revealed, for the first time, that PA generates ROS, and that this ROS accumulation induced the Bcl signaling pathway.

Human-yeast genetic interaction for disease network: systematic discovery of multiple drug targets

  • Suk, Kyoungho
    • BMB Reports
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    • 제50권11호
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    • pp.535-536
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    • 2017
  • A novel approach has been used to identify functional interactions relevant to human disease. Using high-throughput human-yeast genetic interaction screens, a first draft of disease interactome was obtained. This was achieved by first searching for candidate human disease genes that confer toxicity in yeast, and second, identifying modulators of toxicity. This study found potentially disease-relevant interactions by analyzing the network of functional interactions and focusing on genes implicated in amyotrophic lateral sclerosis (ALS), for example. In the subsequent proof-of-concept study focused on ALS, similar functional relationships between a specific kinase and ALS-associated genes were observed in mammalian cells and zebrafish, supporting findings in human-yeast genetic interaction screens. Results of combined analyses highlighted MAP2K5 kinase as a potential therapeutic target in ALS.

곶자왈 지역의 의약물질과 농약의 오염수준과 생태독성영향 (Contamination Levels of Pharmaceuticals and Pesticides in the Gotjawal Regions of Jeju Island and Associated Ecotoxicities)

  • 강하병;고수림;최윤송;이상우;고영림;오달영;최경호
    • 한국환경보건학회지
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    • 제39권5호
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    • pp.426-437
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    • 2013
  • Objective: Gotjawal refers to a special geographical designation found in Jeju Province, Korea, where vegetation forms over a rocky area. Due to the important ecological value of Gotjawal, international concern about such areas is growing. However, only limited information is available regarding environmental contamination of Gotjawal. This study was conducted in order to investigate the levels of contamination and associated ecotoxicological effects of surface water bodies in Gotjawal. Methods: Surface water samples were collected at three sampling sites in two Gotjawal areas and were analyzed for several pharmaceuticals and pesticides in consideration of the potential sources of contamination. The ecotoxicity of the samples was measured using water fleas (Daphnia magna and Moina macrocopa) and zebrafish (Danio rerio). In addition, effects on the gene transcription of zebrafish were investigated following exposure to the samples. Results: Nine pharmaceuticals were detected in the samples, but none of the target pesticides were detected. Following acute exposure to two surface water samples, the survival of waterfleas was significantly reduced, but reproduction was not affected. In zebrafish, time-to-hatch was delayed and fry survival was decreased in some samples. On the other hand, at the transcriptional level, there were no genes significantly influenced by exposure to the samples. Conclusion: This is the first study investigating environmental contamination in Gotjawal areas and associated ecotoxicities. Further studies are warranted to identify the cause of acute Daphnia toxicity and to determine potential consequences of longer-term exposure in Gotjawal areas.

Polyphenol-rich fraction from Ecklonia cava (a brown alga) processing by-product reduces LPS-induced inflammation in vitro and in vivo in a zebrafish model

  • Kim, Seo-Young;Kim, Eun-A;Kang, Min-Cheol;Lee, Ji-Hyeok;Yang, Hye-Won;Lee, Jung-Suck;Lim, Tae Il;Jeon, You-Jin
    • ALGAE
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    • 제29권2호
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    • pp.165-174
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    • 2014
  • Ecklonia cava is a common edible brown algae that is plentiful in Jeju Island of Republic of Korea. Polyphenols from E. cava have strong anti-inflammatory activity. However, a large number of the by-products from E. cava processing are discarded. In the present study, to utilize these by-products, we assessed the anti-inflammatory activity of the polyphenol-rich fraction (PRF) from E. cava processing by-product (EPB) in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells. Four compounds, namely eckol, eckstolonol, dieckol, and phlorofucofuroeckol-A, were isolated and identified from PRF. We found that PRF suppressed the production of nitric oxide (NO), inducible nitric oxide synthase, and cyclooxygenase-2 in the LPS-induced cells. Furthermore, the protective effect of PRF was investigated in vivo in LPS-stimulated inflammation zebrafish model. PRF had a protective effect against LPS-stimulated toxicity in zebrafish embryos. In addition, PRF inhibited LPS-stimulated reactive oxygen species and NO generation. According to the results, PRF isolated from EPB could be used as a beneficial anti-inflammatory agent, instead of discard.

Larvicidal potency of selected xerophytic plant extracts on Culex pipiens (Diptera: Culicidae)

  • ABUTAHA, Nael;AL-MEKHLAFI, Fahd A.;AL-KERIDIS, Lamya Ahmed;FAROOQ, Muhammad;NASR, Fahd A.;AL-WADAAN, Muhammad
    • Entomological Research
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    • 제48권5호
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    • pp.362-371
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    • 2018
  • Chemical insecticides released into the environment may have adverse biological effects. Therefore, there is a need for ecofriendly insecticides for mosquito control. Xerophytic plant extracts that may provide more ecofriendly active component were evaluated against Culex pipiens 4th instars. Plant extracts prepared using different solvents with a Soxhlet apparatus and different concentrations were tested against Culex pipiens larvae. The effects were observed at 24 h and 72 h intervals and $LD_{50}$ and $LD_{90}$ values determined. Chloroform ($CHCl_3$) and ethyl acetate (EtOAc) extracts of Althaea ludwigii were the most effective against Cx. pipiens $4^{th}$ instars, but were highly dependent on extract concentrations and exposure time. Results suggest that A. ludwigii extracts contain bioactive compounds, such as phenols and saponins, that may provide effective Cx. pipienslarval control. However, the extract was found to be toxic to zebrafish larvae, and may be toxic to other aquatic fauna. Further studies to determine the active components and toxicity to other fauna are needed.

Preventive effects of sea cucumber (Apostichopus japonicus) ethanol extract on palmitate-induced vascular injury in vivo

  • Zhang, Chunying;Cha, Seon-Heui
    • Fisheries and Aquatic Sciences
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    • 제25권2호
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    • pp.90-100
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    • 2022
  • Cardiovascular diseases (CVDs) have posed serious public health problems, accounting for nearly 30% of mortality worldwide and their incidence is still increasing. Therefore, new treatment resources are necessary to prevent or manage the ever-increasing population of patients with CVDs. Sea cucumber is well known for its medical and health benefit effects, but it is not well known what/how effect it has on vascular disease. In the present study, we examined the protect effect of sea cucumber, Apostichopus japonicus 80% ethanol extract (AJE) on zebrafish embryo with the stimulation of free fatty acid, palmitate (PA). In vivo study showed that AJE can attenuate PA-induced toxicity through relieving the rapid heartbeat, increasing the survival rate and reducing the malformation in both wild type and Tg (fli1a:eGFP) transgenic zebrafish lines. Additionally, compare with PA treated embryos, the yolk sac area, body length, axial vascular segment (AVS) and intersegmental vessel (ISV) of the co-treatment group of AJE and PA were comparable to the control group. Moreover, AJE lowered the expression of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and inflammation-related genes induced by PA, and inhibited PA-induced vascular development disorders. Our data preliminarily verify that AJE could be a candidate resource for the prevention or therapy of CVDs.

Effects of Size, Impurities, and Citrate Capping on the Toxicity of Manufactured Silver Nano-particles to Larval Zebrafish (Danio rerio)

  • Kim, Jungkon;Park, Yena;Lee, Sangwoo;Seo, Jihyun;Kwon, Dongwook;Park, Jaehong;Yoon, Tae-Hyun;Choi, Kyungho
    • 한국환경보건학회지
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    • 제39권4호
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    • pp.369-375
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    • 2013
  • Objectives: This study was conducted to identify factors determining the toxicity of manufactured silver nano-particles (AgNPs) on aquatic organisms. Methods: For this purpose, we prepared several AgNPs with varied characteristics, including hydrodynamic size (nano-$^{ABC}Ag^{Cit}\;vs$-sized-$^{ABC}Ag^{Cit}$), impurities ($^{ABC}Ag$ stock vs $^{ABC}Ag$), and citrate capping ($^{ABC}Ag^{Cit}$), using a commercially available manufactured AgNP ($^{ABC}Ag$ stock). Acute tests were conducted using larval zebrafish (Danio rerioI). In addition, in order to determine the ecotoxicological potentials of various capping agents, toxicity tests were conducted with microbes, waterfleas, and fish for eight different capping agents that are used for NPs. Results: The toxicity of AgNPs in terms of 96 h fish $LC_{50}$ increased in the following order: $^{ABC}Ag$ stock < $^{ABC}Ag=^{ABC}Ag^{Cit}=nano-^{ABC}Ag^{Cit}$ < ${\mu}$-sized-$^{ABC}Ag^{Cit}$ < $AgNO_3$. After removing impurities by dialysis, 96 h $LC_{50}$ value decreased significantly from $126.6{\mu}g/L$ (95% confidence intervals [CI]: 107.0-146.2) ($^{ABC}Ag$ stock) to $78.6{\mu}g/L$ (CI: 72.7-84.8) ($^{ABC}Ag$). For ${\mu}$-sized-$^{ABC}Ag^{Cit}$ (ranging between 3.9 and 40.6 nm) and $^{ABC}Ag^{Cit}$ (40.6 nm and $9.1{\mu}m$), the 96 h $LC_{50}$ of the former ($43.9{\mu}g/L$, CI: 36.0-51.7) was approximately two-fold lower than that of the latter ($87.0{\mu}g/L$, CI: 73.5-100.3). Conclusions: In this study, we found that for acute lethality, the contribution of impurities and particle size was significant, but that of citrate was negligible.

Flow-through fish test를 이용한 Phosphamidon과 Profenofos의 생물농축계수의 측정 (Determination of Bioconcentration Factor on Phosphamidon and Profenofos by Flow-through Fish Test)

  • 민경진;차춘근;서설
    • 한국식품위생안전성학회지
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    • 제15권2호
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    • pp.137-143
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    • 2000
  • Zebrafish(Brachydanio rerio)를 실험어류로 하여 phosphamidon과 profenofos의 생물농축계수(bioconcentration factor: BCF)와 배설속도상수(depuration rate constant) 및 LC$_{50}$를 측정하였다. Phosphamidon의 24, 48, 72, 96시간 LC50 모두 l00 mg/l 이상으로 측정되었다. Phosphamidon 1 mg/l(고농도)와 0.2 mg/l(저농도)에서 어류 체내에서의 농축정도는 두 농도군에서 각각 12시간 이후에 정류상태에 도달하여 168시간동안 거의 일정하였고, BCF값도 12시간에서 16시간 사이에 고농도(0.89, n=7)와 저농도(0.96, n=7)모두 1미만으로 낮게 나타났다. Phosphamidon의 배설속도상수는 고농도와 저농도에서 각각 0.21 h-1과 0.18 h-1 이었고, 반감기는 각각 3.30및 3.85시간으로 측정되었다. 고농도와 저농도에서 각각 12시간 및 8시간 이후에는 g당 0.07 및 0.04 $\mu\textrm{g}$이하로 떨어져 대부분 배설된다는 것을 알 수 있었다. Profenofos의 24, 48, 72, 96시간 LC50는 각각 2.9, 2.6, 2.2, 2.O mg/l로 측정되었다. Profenofos의 96시간 LC$_{50}$ 농도의 1/100농도(0.02 mg/l)와 1/500농도(0.004 mg/l)에서 어류체내에서의 농축정도는 phosphamidon과 마찬가지로 12시간 이후에 정류상태에 도달하여 168시간동안 거의 일정하였고, BCF값은 12시간에서 168시간 사이에 96시간 LC$_{50}$농도의 1/100농도와 1/500농도에서 각각 111.3(n=7)과 141.9(n=7)로 측정되었다. Profenofos의 배설속도상수는 96시간 LC50 농도의 1/100농도와 1/500농도에서 각각 0.10 $h^{-1}$과 0.09$h^{-1}$h-1이었고, 반감기는 각각 6.93 및 7.70시간으로 측정되었다. 각각의 농도에서 12시간 및 8시간 이후에는 g당 0.19$\mu\textrm{g}$ 및 0.18$\mu\textrm{g}$이하로 떨어짐을 알 수 있었다. Phosphamidon과 profenofos의 급성어독성은 profenofos가 높았고, BCF profenofos가 phosphamidon보다 약 100배 정도 높게 나타났으며, 배설속도는 phosphamidon이 profenofos보다 약 2배 정도 빨랐다.

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와송 에틸아세테이트 분획물의 항산화 효능에 관한 연구 (A Study on the Antioxidative Effect of Orostachys Japonicus A. Berger Ethyl Acetate Fraction)

  • 임은경;양재찬
    • 한국응용과학기술학회지
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    • 제38권1호
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    • pp.118-125
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    • 2021
  • 본 연구에서 사용된 와송(Orostachys japonica A. Berger)은 암 치료를 위한 민간요법으로 오랫동안 사용되어 온 약초이다. 본 연구에서는 와송(Orostachys japonica A. Berger) 에틸아세테이트 분획물의 항산화 효능 활성에 대하여 실험한 결과를 보고한다. 와송(Orostachys japonica A. Berger) 에틸아세테이트 분획물의 항산화 효능은 0.10 mg/mL 농도에서 78.54%의 DPPH 라디칼 소거활성을 보였고, 73.48%의 ABTS+ 라디칼 소거활성을 나타내어 항산화 효과가 있는 것을 확인하였다. 또한 대체실험동물 모델인 제브라피쉬를 이용한 독성실험 결과에서는 모든 농도에서 100%의 배아 생존율을 보이고 응고 또는 부화지연을 관찰할 수 없어 독성이 없는 것으로 나타났으며, UV-B조사에 의해 유도된 ROS생성은 와송 에틸아세테이트 분획물을 처리한 모든 larvae에서 전체적으로 형광강도가 감소하였다. 특히 3 ㎍/mL 농도에서 양성대조군 대비 35.7%의 감소율을 보여 효과적으로 ROS 생성을 억제하였음을 확인하였다. 위와 같은 결과로 미루어보아, 와송 에틸아세테이트 분획물은 천연 항산화제로서 화장품 분야에서 응용 가능성이 있을 것으로 기대한다.