• Journal of the Korean Applied Science and Technology
• /
• v.41 no.2
• /
• pp.292-304
• /
• 2024

This study compared and evaluated the antioxidant activities of Symphoricarpos albus(S. albus) extract and fermented extract. Antioxidant activity was measured by DPPH radical scavenging, FRAP, and ABTS. Concentrations were measured at 200, 100, 50, and 10 ㎍/mL, and antioxidant activity increased in a concentration-dependent manner. S. albus leaves fermented extracts had the highest antioxidant activity. And this study evaluated the safety and tail regeneration of S. albus extract using zebrafish model embryos. Zebrafish are in the spotlight as an alternative animal and can be used for cosmetic research. Zebrafish embryos were collected and evaluated for coagulation rate, hatching rate, and cardiotoxicity. As a result, it was toxic at concentrations above 100 ㎍/ml. The tail was cut and the regenerative effect was observed for 3 days. As a result, from 72 hours, S. albus 200ug/ml leaf extract showed a 17% regenerative effect compared to the control group. These results suggest that S. albus can be used as a natural material for antioxidant and regeneration for skin improvement.

• Molecular & Cellular Toxicology
• /
• v.5 no.1
• /
• pp.23-31
• /
• 2009

To compare the effects of nanometer-sized silver ions and support materials (nano-silver coating material, NM-silver) and silver ions, we exposed zebrafish embryos to both types of nano-silver ions and compared the acute responses during embryogenesis. The amount of silver in the NM-silver (17.16%) was greater than that in the silver ion (4.56%). Both of these materials have different atomic compositions. The silver ion-exposed groups (10 and 20 ppt) showed lower survival rates than the NM-silver-exposed groups (10 and 20 ppt). NM-silver penetrated the skin and blood tube of zebrafish larvae as aggregated particles, whereas, silver ions penetrated the organelles, nucleus and yolk in a spread-out pattern. Micro-array analysis of RNA from zebrafish larvae (72 hours post-fertilization) that were treated with either NM-silver or silver ions, showed alteration in expression of the BMP, activin, TGF-$\beta$, and $GSK3{\beta}$ genes pathway. Additionally, $GSK3{\beta}$ gene pathway for apoptosis that was related with left-right asymmetry. Gene expression changes in the NM-silver or silver ions-treated zebrafish embryo led to phenotypic changes in the hatched larvae, reflecting increased apoptosis and incomplete formation of an axis.

• Journal of Animal Reproduction and Biotechnology
• /
• v.35 no.1
• /
• pp.28-34
• /
• 2020

Imazosulfuron is globally considered as a relatively safe herbicide that controls plant growth by interfering with amino acid synthesis. It is stable, persists in the soil, and has low toxicity; however, studies about the toxic effects of imazosulfuron on non-targeted aquatic vertebrates are scarce. In this study, imazosulfuron was able to induce acute lethality on zebrafish embryos within 48 h. Imazosulfuron also had adverse effects on heartbeats and induced abnormal development with pericardial edema and scoliosis. Moreover, apoptosis and oxidative stress were increased by imazosulfuron in a dose-dependent manner. Thus, all our results showed that imazosulfuron has toxic effects on zebrafish embryogenesis.

• Journal of Environmental Health Sciences
• /
• v.50 no.3
• /
• pp.212-220
• /
• 2024

Background: 2-Ethylhexyl diphenyl phosphate (EHDPP) is widely used as a flame-retardant plasticizer in the production of polyvinyl chloride, adhesives, and food packaging. This chemical has been frequently detected in water, sediment, and indoor environments, and its lipophilicity raises concerns about bioaccumulation. Objectives: In this study, the effects of EHDPP on the development, behavioral changes, and growth hormone (GH) endocrine system of zebrafish larvae were investigated. Methods: Fertilized embryos were exposed to various concentrations (control, solvent control, 0.07, 0.7, 7, 70, and 700 ㎍/L) of EHDPP for 96 h. Developmental toxicity endpoints were observed daily. Behavioral changes under light-dark-light conditions and changes in hormones and genes related to GH/insulin-like growth factors (IGFs) axis were determined. Results: Significant decreases in survival, body length and moving distance were observed in zebrafish larvae exposed to 70 and 700 ㎍/L EHDPP. The concentrations of GH and IGF-1 were significantly decreased in zebrafish larvae exposed to 70 and 700 ㎍/L EHDPP. This change was well supported by changes in the transcription of genes involved in GH, IGF, IGF receptors, and IGF binding proteins. Conclusions: Our observations showed that exposure to 70 and 700 ㎍/L EHDPP could disrupt the feedback circuits of the GH/IGFs axis, ultimately leading to developmental toxicity, hypoactivity, and mortality.

• Journal of Microbiology and Biotechnology
• /
• v.30 no.6
• /
• pp.920-925
• /
• 2020

In India, nanotechnology has been used in therapeutic applications for several millennia. One example of a traditional nanomedicine is Rajath Bhasma (also called calcined silver ash), which is used as an antimicrobial and for the treatment of various ailments and conditions such as memory loss, eye diseases, and dehydration. In this study, we aimed to characterize the physical composition and morphology of Rajath Bhasma and its suitability for use as a non-toxic antimicrobial agent. First, Rajath Bhasma was physically characterized via i) Fourier-transform infrared spectroscopy to analyze the surface functional groups, ii) scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy to observe the morphology and elemental composition, and iii) X-ray diffraction to determine the crystalline phases. Thereafter, functional characterization was performed through toxicity screening using zebrafish embryos and through antimicrobial activity assessment against gram-positive (Staphylococcus epidermidis) and gram-negative (Escherichia coli) bacteria. Rajath Bhasma was found to harbor alkene, hydroxyl, aldehyde, and amide functional groups originating from biological components on its surface. The main component of Rajath Bhasma is silver, with particle size of 170-210 nm, and existing in the form of spherical aggregates with pure crystalline silver structures. Furthermore, Rajath Bhasma did not exert toxic effects on zebrafish embryos at concentrations below 5 ㎍/ml and exhibited effective antimicrobial activity against both gram-positive and gram-negative bacteria. The present results indicate that Rajath Bhasma is a potentially effective antimicrobial agent without toxicity when used at concentrations below 5 ㎍/ml.

• Korean Journal of Environmental Biology
• /
• v.38 no.2
• /
• pp.271-277
• /
• 2020

Toxicities to many organs caused by humidifier disinfectants have been reported. Recently, humidifier disinfectants have been reported to cause cardiovascular, embryonic, and hepatic toxicities. This study was designed to investigate the toxic mechanism of humidifier disinfectants and compare toxicity in a cellular model and a zebrafish animal model. Because brain toxicity and skin toxicity have been less studied than other organs, we evaluated toxicity in a human dermal cell line and zebrafish under various concentrations of humidifier disinfectants that included polyhexamethyleneguanidine phosphate (PHMG), oligo-[2-(2-ethoxy)-ethoxyethyl-guanidinium-chloride] (PGH) and methylchloroisothiazolinone/methylisothiazolinone (CMIT/MIT). A human dermal fibroblast cell line was treated with disinfectants (0, 2, 4, 6, 8, and 16 mg L^-1) to compare their cytotoxicity. The fewest PHMG-treated cells survived (up to 33%), while 49% and 40% of the PGH- and CMIT/MIT-treated cells, respectively, survived. The quantification of oxidized species in the media revealed that the PHMG-treated cells had the highest MDA content of around 28 nM, while the PGH- and CMIT/MIT-treated cells had 13 and 21 nM MDA, respectively. As for brain toxicity, treatment of the zebrafish tank water with CMIT/MIT (final 40 mg L^-1) for 30 min resulted in a 17-fold higher production of reactive oxygen species (ROS) than in the control. Treatment with PGH or PHMG (final 40 mg L^-1) resulted in 15- and 11-fold higher production, respectively. The humidifier disinfectants (PHMG, PGH, and CMIT/MIT) showed severe dermal cell toxicity and brain toxicity. These toxicities may be relevant factors in understanding why some children have language disorders, motor delays, and developmental delays from exposure to humidifier disinfectants.

• Biomolecules & Therapeutics
• /
• v.26 no.6
• /
• pp.599-607
• /
• 2018

Fasiglifam (TAK-875) a G-protein coupled receptor 40 (GPR40) agonist, significantly improves hyperglycemia without hypoglycemia and weight gain, the major side effects of conventional anti-diabetics. Unfortunately, during multi-center Phase 3 clinical trials, unexpected liver toxicity resulted in premature termination of its development. Here, we investigated whether TAK-875 directly inflicts toxicity on hepatocytes and explored its underlying mechanism of toxicity. TAK-875 decreased viability of 2D and 3D cultures of HepG2, a human hepatocarcinoma cell line, in concentration-(>$50{\mu}M$) and time-dependent manners, both of which corresponded with ROS generation. An antioxidant, N-acetylcysteine, attenuated TAK-875-mediated hepatotoxicity, which confirmed the role of ROS generation. Of note, knockdown of GPR40 using siRNA abolished the hepatotoxicity of TAK-875 and attenuated ROS generation. In contrast, TAK-875 induced no cytotoxicity in fibroblasts up to $500{\mu}M$. Supporting the hepatotoxic potential of TAK-875, exposure to TAK-875 resulted in increased mortality of zebrafish larvae at$25{\mu}M$. Histopathological examination of zebrafish exposed to TAK-875 revealed severe hepatotoxicity as manifested by degenerated hypertrophic hepatocytes with cytoplasmic vacuolation and acentric nuclei, confirming that TAK-875 may induce direct hepatotoxicity and that ROS generation may be involved in a GPR40-dependent manner.

• Journal of Ginseng Research
• /
• v.41 no.1
• /
• pp.103-112
• /
• 2017

Background: 20(S)-Protopanaxadiol 20-O-D-glucopyranoside, also called compound K (CK), exerts antidiabetic effects that are mediated by insulin secretion through adenosine triphosphate (ATP)-sensitive potassium ($K_{ATP}$) channels in pancreatic ${\beta}$-cells. However, the antidiabetic effects of CK may be limited because of its low bioavailability. Methods: In this study, we aimed to enhance the antidiabetic activity and lower the toxicity of CK by including it with ${\beta}$-cyclodextrin (CD) (CD-CK), and to determine whether the CD-CK compound enhanced pancreatic islet recovery, compared to CK alone, in an alloxan-induced diabetic zebrafish model. Furthermore, we confirmed the toxicity of CD-CK relative to CK alone by morphological changes, mitochondrial damage, and TdT-UTP nick end labeling (TUNEL) assays, and determined the ratio between the toxic and therapeutic dose for both compounds to verify the relative safety of CK and CD-CK. Results: The CD-CK conjugate ($EC_{50}=2.158{\mu}M$) enhanced the recovery of pancreatic islets, compared to CK alone ($EC_{50}=7.221{\mu}M$), as assessed in alloxan-induced diabetic zebrafish larvae. In addition, CD-CK ($LC_{50} =20.68{\mu}M$) was less toxic than CK alone ($LC_{50}=14.24{\mu}M$). The therapeutic index of CK and CD-CK was 1.98 and 9.58, respectively. Conclusion: The CD-CK inclusion complex enhanced the recovery of damaged pancreatic islets in diabetic zebrafish. The CD-CK inclusion complex has potential as an effective antidiabetic efficacy with lower toxicity.

• The Korean Journal of Pesticide Science
• /
• v.18 no.1
• /
• pp.14-20
• /
• 2014

This study is aimed to search the possibility of developmental toxicity test using the zebrafish from the pesticide. We selected herbicides alachlor and butachlor, reported for fish toxicity, and insecticide fipronil reported for the high fish toxicity and the honey bee risk among the pesticides with high usability for the examples of the pesticides in this experiment. In this study, we showed those effects on the zebrafish embryo development by exposing different kinds of pesticide with different concentration and exposed time periods. As a result, the rates of hatching and abnormality of the zebrafish embryo after treatments of alachlor were increased in 24-48 hpf group, and the juvenile fishes in every group exposed to $40{\mu}M$ or more of alachlor displayed sever morphological changes such as bent tails, edema and activity failures. In case of the butachlor, the rates of hatching and the abnormality in 24-48 hpf group were higher than the other groups exposed in different time periods. The fatality before hatching was high in $40{\mu}M$ or more of butachlor treatment, and entire zebrafish embryos in 48 hpf group died before hatching. All the living juvenile fishes showed morphological changes as like as the treatment of alachlor. The rate of hatching and the survival of the zebrafish embryo by the fipronil were higher than other pesticides. However, morphological changes such as bent tails were observed from the most of living juvenile fishes. Therefore, the effects of three different pesticides with different concentrations and exposing time periods on the development of zebrafish embryos showed that all the pesticides effects were proportional to the concentration, and exposing time periods may cause the morphological abnormality.

• Korean Journal of Environmental Biology
• /
• v.41 no.1
• /
• pp.41-53
• /
• 2023

E171, a mixture of titanium dioxide, has been widely used as a food additive due to its whitening effect and low toxicity. However, it has been proven that E171 is no longer safe for public health. So far, there are insufficient studies on the toxic effects of E171 on organisms especially using standardized test methods. In this study, toxicity assessments of E171 to two aquatic species, water flea (Daphnia magna) and zebrafish (Danio rerio), were performed using modified standardized test methods based on the physicochemical properties of E171. The hydrodynamic diameter, polydispersity index, and turbiscan stability index (TSI) were measured to ensure the dispersion stability of E171 in exposure media during the test period. The EC₅₀ for immobilization of water flea was 141.7 mg L^-1 while zebrafish was not affected until 100 mg L^-1 of E171. Measurements of reactive oxygen species (ROS) and antioxidant enzyme activities confirmed that E171 induced oxidative stress, leading to the activation of superoxide dismutase and catalase in both water flea and zebrafish, although the expression of antioxidant enzyme genes differed between species. These results suggested the potential risk of E171 to aquatic organisms and provided toxicological insights into the impacts of E171 on the environment.