Publications by authors named "Kyeongnam Kim"

12 Publications

  • Page 1 of 1

Developmental toxicity of 3-phenoxybenzoic acid (3-PBA) and endosulfan sulfate derived from insecticidal active ingredients: Abnormal heart formation by 3-PBA in zebrafish embryos.

Ecotoxicol Environ Saf 2021 Aug 26;224:112689. Epub 2021 Aug 26.

Department of Integrative Biology, Kyungpook National University, Daegu 41566, Republic of Korea; Department of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address:

Pyrethroid and organochlorine insecticides are enormously used to control agricultural and indoor insect pests. The metabolites of pyrethroid and endosulfan were used to evaluate environmental toxicities using a representative animal model, zebrafish (Danio rerio) embryos in this study. The LC values in 3-phenoxy benzoic acid (3-PBA) and endosulfan sulfate (ES) were 1461 μg/L and 1459 μg/L, respectively. At the concentration of 2000 μg/L, spine curvature was observed in the ES-treated embryos. ES showed seizure-like events with an EC value of 354 μg/L. At the concentration of 1000 μg/L, the pericardial edema was observed in 3-PBA-treated embryos. The inhibition of heart development and the reduction of beating rates were observed in Tg(cmlc2:EGFP) embryos after the exposure to 3-PBA. Down-regulation of the vmhc gene coding ventricular myosin during heart development was significantly found in 3-PBA-treated embryos at 48 hpf, but recovered afterward. It indicates that ventricular malformation occurred at the initial stage of 3-PBA exposure. Considered together, both 3-PBA and ES need public concerns with periodic monitoring of these metabolites in households and agricultural areas to prevent humans and environmental organisms from their unexpected attacks.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112689DOI Listing
August 2021

Acute toxicity of the insecticide EPN upon zebrafish (Danio rerio) embryos and its related adverse effects: Verification of abnormal cardiac development and seizure-like events.

Ecotoxicol Environ Saf 2021 Oct 26;222:112544. Epub 2021 Jul 26.

Department of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea; Department of Integrative Biology, College of Agriculture and Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address:

Toxicological studies of O-ethyl-O-(4-nitrophenyl) phenylphosphonothioate (EPN) to aquatic vertebrates have been reported, but no reports on toxic mechanism was reported. As zebrafish (Danio rerio) embryos were exposed to EPN, no changes in their survival and hatching rates were observed until 96 h post fertilization (hpf), even at the highest treated concentration of 500 μg/L. In both 250 μg/L and 500 μg/L, edemas were observed in the heart and yolk sac, and a blood pool was also found. Acridine orange staining confirmed apoptotic phynotype, which was the strongest in embryos at 48 hpf. No noticeable difference in the formation and the shape of blood vessels of Tg(fli1a:EGFP) was observed. However, the total body length and number of somite were decreased. Heart formation in Tg(cmlc2:EGFP) were not properly proceeded, and the ventricle did not beat normally at 500 μg/L level. Cardiac development-related genes, myl7 and nppa, were significantly down- and up-regulated in a concentration-dependent manner. The slowed heartbeat was confirmed using Tg(gata1:EGFP), showing stagnant blood flow and seizure-like events were observed. Altogether, EPN can be the cause for the abnormal heart development accompanied by blood stagnation in embryos, interfering normal development with their inner circulatory system.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112544DOI Listing
October 2021

Transcriptomic evaluation on methyl bromide-induced phytotoxicity in Arabidopsis thaliana and its mode of phytotoxic action via the occurrence of reactive oxygen species and uneven distribution of auxin hormones.

J Hazard Mater 2021 10 17;419:126419. Epub 2021 Jun 17.

Department of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of Korea; Department of Integrative Biology, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address:

The increase in worldwide trade has caused the quality maintenance of commercialized agriproducts to be crucial in keeping its economic value. In recent years, methyl bromide (MB) has been used dominantly during quarantine and pre-shipment, despite it being an environmental hazard with global repercussions. Through this study, it was shown that Arabidopsis thaliana's 2 h exposure to the MB treatment displayed no signs of phytotoxicity, whereas its 4 h exposure significantly interfered with growth. The transcriptomic analysis found the molecular modifications in A. thaliana after the MB fumigation with the up-regulation of genes specifically relative to the abiotic and oxidative stress, and the down-regulation of auxin transporter genes. Some important gene expressions were verified by RT-qPCR and their expression patterns were similar. Oxidative stresses via the reactive oxygen species (ROS) in relation to MB phytotoxicity were confirmed with the increased malondialdehyde in MB-4h-treated A. thaliana. Uneven distribution of auxins via lower expression of auxin transporter genes was also determined using UPLC-ESI-QqQ MS. Application of two ROS scavengers such as N-acetyl-cysteine and L-glutathione minimized MB phytotoxic effect in A. thaliana. Therefore, MB caused severe oxidative stress, and alternatives regarding the use of MB should be considered.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126419DOI Listing
October 2021

Molecular Mechanisms of Anti-Melanogenic Gedunin Derived from Neem Tree () Using B16F10 Mouse Melanoma Cells and Early-Stage Zebrafish.

Plants (Basel) 2021 Feb 9;10(2). Epub 2021 Feb 9.

Department of Applied Biosciences, Kyungpook National University, Daegu 41566, Korea.

Melanogenesis represents a series of processes that produce melanin, a protective skin pigment (against ultraviolet rays), and determines human skin color. Chemicals reducing melanin production have always been in demand in the cosmetic market because of skincare interests, such as whitening. The main mechanism for inhibiting melanin production is the inhibition of tyrosinase (TYR), a key enzyme for melanogenesis. Here, we evaluated gedunin (Ged), a representative limonoid, for its anti-melanogenesis action. Melanin production in vitro was stimulated by alpha-melanocyte stimulating hormone (α-MSH) in B16F10 mouse melanoma cells. Ged reduced α-MSH-stimulated melanin production, inhibiting TYR activity and protein amount. We confirmed this result in vivo in a zebrafish model for melanogenesis. There was no sign of toxicity and malformation of zebrafish embryos during development in all treated concentrations. Ged reduced the number of produced zebrafish embryo pigment dots and melanin contents of embryos. The highly active concentration of Ged (100 µM) was much lower than the positive control, kojic acid (8 mM). Hence, Ged could be a fascinating candidate for anti-melanogenesis reagents.
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http://dx.doi.org/10.3390/plants10020330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914499PMC
February 2021

Combined toxicity of dimethyl sulfoxide (DMSO) and vanadium towards zebrafish embryos (Danio rerio): Unexpected synergistic effect by DMSO.

Chemosphere 2021 May 28;270:129405. Epub 2020 Dec 28.

Department of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea; Department of Integrative Biology, Kyungpook National University, Daegu, 41566, Republic of Korea. Electronic address:

Dimethyl sulfoxide (DMSO) is produced in nature and is known to be a source of carbon and sulfur for marine microorganisms. It is currently used in many biological experiments, pharmaceutical preparations, and energy-producing systems such as lithium batteries. Therefore, the toxicity of DMSO has been studied because of its various implications to living organisms; however, such studies are largely limited to measuring individual toxicity whereas the combined toxicity of DMSO with other compounds has rarely been investigated. In the present study, the combined acute toxicity of 0.1% and 0.5% DMSO with vanadium was investigated in zebrafish embryos; the LC values of these combinations were 62.0 and 6.38 ppm, respectively. In individual toxicity tests, neither DMSO nor vanadium caused such mortality levels. Therefore, both 0.1% and 0.5% DMSO had a synergistic effect with vanadium, and this result was confirmed using an independent action model. This combined toxicity delayed the development of zebrafish embryos and caused pericardial edema. The synergistic effect of DMSO and vanadium was found to be related to reduced pH and inhibition of cytochrome c oxidase activity. Given its potential synergistic toxicity to aquatic organisms, the introduction of DMSO into the environment should be investigated and routinely monitored.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129405DOI Listing
May 2021

Molecular mechanisms of developmental toxicities of azoxystrobin and pyraclostrobin toward zebrafish (Danio rerio) embryos: Visualization of abnormal development using two transgenic lines.

Environ Pollut 2021 Feb 17;270:116087. Epub 2020 Nov 17.

Department of Integrative Biology, Kyungpook National University, Daegu, 41566, Republic of Korea; School of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea. Electronic address:

Azoxystrobin (AZ) and pyraclostrobin (PY) are strobilurin fungicides that inhibit fungal mitochondrial respiration. In this study, a representative model, zebrafish (Danio rerio), was used as a test species for acute and developmental toxicity. Survival and malformation rates were observed only PY-treated embryos, with an LC value of 77.75 ppb accompanied by a dramatic decrease in hatching rate, while AZ did not show great mortality. Morphological changes were observed in PY-treated embryos with the occurrence of pericadial edema at 25 ppb. A delay in growth was observed after treatment with pyraclostrobin at 50 ppb. Use of genetically engineered Tg(cmlc:EGFP) allowed fluorescence observation during heart development. PY interfered with normal heart development via upregulation of the nppa gene responsible for the expression of natriuretic peptides. Heart function was dramatically reduced as indicated by reduced heart rates. Increased expression of the nppa gene was also seen in AZ-treated embryos. The expression level of cyp24a1 was also up-regulated, while ugt1a1 and sult1st6 were down-regulated after treatment of zebrafish embryos with AZ or PY. Overall, strobilurin fungicides might inhibit normal heart formation and function within the range of concentrations tested.
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http://dx.doi.org/10.1016/j.envpol.2020.116087DOI Listing
February 2021

Acute toxicities of fluorene, fluorene-1-carboxylic acid, and fluorene-9-carboxylic acid on zebrafish embryos (Danio rerio): Molecular mechanisms of developmental toxicities of fluorene-1-carboxylic acid.

Chemosphere 2020 Dec 11;260:127622. Epub 2020 Jul 11.

School of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea. Electronic address:

In this study, fluorene (FL), FL-1-carboxylic acid (FC-1), and FL-9-carboxylic acid (FC-9) were investigated to understand their acute toxicity by measuring inhibitory effects on hatching rates and developmental processes of zebrafish embryos (Danio rerio). For exposure concentrations up to 3000 μg/L, FC-1 alone showed acute toxicity at 1458 μg/L for LC value. FC-1 caused yolk sac and spinal deformities, and pericardial edema. Molecular studies were undertaken to understand FC-1 toxicity examining 61 genes after exposure to 5 μM (equivalent to LC value of FC-1) in embryos. In the FC-1-treated embryos, the expression of the cyp7a1 gene, involved in bile acid biosynthesis, was dramatically decreased, while the expression of the Il-1β gene involved in inflammation was remarkably increased. In addition to these findings, in FC-1-treated embryos, the expression of nppa gene related to the differentiation of the myocardium was 3-fold increased. On the other hand, cyp1a, cyp3a, ugt1a1, abcc4, mdr1, and sult1st1 responsible for detoxification of xenobiotics were upregulated in FC-9-treated embryos. Taken together, carboxylation on carbon 1 of FL increased acute toxicity in zebrafish embryos, and its toxicity might be related to morphological changes with modification of normal biological functions and lowered defense ability.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127622DOI Listing
December 2020

Targeted toxicometabolomics of endosulfan sulfate in adult zebrafish (Danio rerio) using GC-MS/MS in multiple reaction monitoring mode.

J Hazard Mater 2020 05 15;389:122056. Epub 2020 Jan 15.

Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address:

Endosulfan sulfate is a major oxidative metabolite of the chlorinated insecticide endosulfan. In this study, a targeted metabolomics approach was used to investigate the toxic mechanisms of endosulfan sulfate in adult zebrafish using the multiple reaction monitoring mode of a GC-MS/MS. The LC of endosulfan sulfate in adult zebrafish was determined and then zebrafish were exposed to endosulfan sulfate at one-tenth the LC (0.1LC) or the LC for 24 and 48 h. After exposure, the fish were extracted, derivatized and analyzed by GC-MS/MS for 379 metabolites to identify 170 metabolites. Three experimental groups (control, 0.1LC and LC) were clearly separated in PLS-DA score plots. Based on the VIP, ANOVA, and fold change results, 40 metabolites were selected as biomarkers. Metabolic pathways associated with those metabolites were identified using MetaboAnalyst 4.0 as follows: aminoacyl-tRNA biosynthesis, valine/leucine/isoleucine biosynthesis, citrate cycle, glycerolipid metabolism, and arginine/proline metabolism. Gene expression studies confirmed the activation of citrate cycle and glycerolipids metabolism. MDA levels of the exposed group significantly increased in oxidative toxicity assay tests. Such significant perturbations of important metabolites within key biochemical pathways must result in biologically hazardous effects in zebrafish.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122056DOI Listing
May 2020

Minimization of energy transduction confers resistance to phosphine in the rice weevil, Sitophilus oryzae.

Sci Rep 2019 10 10;9(1):14605. Epub 2019 Oct 10.

School of Applied Biosciences, Kyungpook National University, Daegu, 41566, Korea.

Infestation of phosphine (PH) resistant insects threatens global grain reserves. PH fumigation controls rice weevil (Sitophilus oryzae) but not highly resistant insect pests. Here, we investigated naturally occurring strains of S. oryzae that were moderately resistant (MR), strongly resistant (SR), or susceptible (wild-type; WT) to PH using global proteome analysis and mitochondrial DNA sequencing. Both PH resistant (PH-R) strains exhibited higher susceptibility to ethyl formate-mediated inhibition of cytochrome c oxidase than the WT strain, whereas the disinfectant PH concentration time of the SR strain was much longer than that of the MR strain. Unlike the MR strain, which showed altered expression levels of genes encoding metabolic enzymes involved in catabolic pathways that minimize metabolic burden, the SR strain showed changes in the mitochondrial respiratory chain. Our results suggest that the acquisition of strong PH resistance necessitates the avoidance of oxidative phosphorylation through the accumulation of a few non-synonymous mutations in mitochondrial genes encoding complex I subunits as well as nuclear genes encoding dihydrolipoamide dehydrogenase, concomitant with metabolic reprogramming, a recognized hallmark of cancer metabolism. Taken together, our data suggest that reprogrammed metabolism represents a survival strategy of SR insect pests for the compensation of minimized energy transduction under anoxic conditions. Therefore, understanding the resistance mechanism of PH-R strains will support the development of new strategies to control insect pests.
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http://dx.doi.org/10.1038/s41598-019-50972-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787191PMC
October 2019

Heart developmental toxicity by carbon black waste generated from oil refinery on zebrafish embryos (Danio rerio): Combined toxicity on heart function by nickel and vanadium.

J Hazard Mater 2019 02 1;363:127-137. Epub 2018 Oct 1.

School of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea. Electronic address:

This study assessed the developmental toxicities of water-soluble carbon black wastes (CBW) extract (1:5, w/v) in zebrafish embryos (Danio rerio). Acute embryonic toxicity was performed following OECD guideline 236. Analysis using ICP-OES revealed that nickel (Ni) and vanadium (V) were predominant in CBW. Embryos exposed to CBW exhibited developmental delay, along with pericardial and yolk sac edemas. Malformed heart chambers were found in the CBW-exposed embryos and heart rates were significantly reduced since 48 h post fertilization (hpf). After RT-qPCR analysis, two cardiac forming-related genes, amhc and nppa responsible for atrial cardiac myofibril assembly and cardiac muscle cell proliferation, were up-regulated after 96 hpf. The increased mortality and delayed yolk-sac development appeared related to CBW-induced decrease in pH to about 5.5. Individual treatments of Ni and V did not cause identical toxic effects as CBW showed. At 100 ppm, V had a pH of approximately 5.5, causing developmental delay and pericardial edema in zebrafish embryos. At the same pH, combined Ni and V induced morphological anomalies and reduced heart rates similar to CBW-exposed embryos. Conclusively, this study demonstrates that environmental runoff is a serious concern, and thus, CBW incineration bottom ash should be treated carefully before disposal in landfills.
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http://dx.doi.org/10.1016/j.jhazmat.2018.09.089DOI Listing
February 2019

Combined toxicity of endosulfan and phenanthrene mixtures and induced molecular changes in adult Zebrafish (Danio rerio).

Chemosphere 2018 Mar 23;194:30-41. Epub 2017 Nov 23.

School of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea. Electronic address:

Individual and combined toxicities of endosulfan (ENDO) with phenanthrene (PHE) were evaluated using zebrafish (Danio rerio) adults. The 96-h LC values for ENDO and PHE were 4.6 μg L and 920 μg L, respectively. To evaluate the mixture toxicity, LC and LC concentrations were grouped into four combinations as ENDO-LC + PHE-LC, ENDO-LC + PHE-LC, ENDO-LC + PHE-LC, and ENDO-LC + PHE-LC, and their acute toxicities were determined. The combination of LC-ENDO and LC-PHE exhibited a synergistic effect. In addition, acetylcholinesterase activity decreased in zebrafish bodies exposed to ENDO with or without PHE. Combined treatments induced higher glutathione S-transferase activity compared to individual treatments. Carboxylesterase activity increased in both heads and bodies of ENDO-treated fishes compared with PHE-treated fishes. Using RT-qPCR technique, CYP1A gene expression significantly up-regulated in all combinations, whereas CYP3A was unchanged, suggesting that enzymes involved in defense may play different roles in the detoxification. CYP7A1 gene responsible for bile acid biosynthesis is dramatically down-regulated after exposure to the synergistic combination exposure, referring that the synergistic effect may be resulted from the reduction of bile production in zebrafishes. Among gender-related genes, CYP11A1 and CYP17A1 genes in female zebrafish decreased after treatment with ENDO alone and combination of LC-ENDO and LC-PHE. This might be related to a reduction in cortisol production. The overall results indicated that ENDO and PHE were toxic to zebrafish adults both individually and in combination, and that their co-presence induced changes in the expression of genes responsible for metabolic processes and defense mechanisms.
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http://dx.doi.org/10.1016/j.chemosphere.2017.11.128DOI Listing
March 2018

Biomarkers indicate mixture toxicities of fluorene and phenanthrene with endosulfan toward earthworm (Eisenia fetida).

Environ Geochem Health 2017 Apr 1;39(2):307-317. Epub 2016 Oct 1.

School of Applied Biosciences, Kyungpook National University, Daegu, 702-701, Korea.

α-Endosulfan and some polycyclic aromatic compounds (PAHs) are persistent in the environment and can reach crop products via contaminated agricultural soils. They may even be present as mixtures in the soil and induce mixture toxicity in soil organisms such as earthworms. In this study, the combined toxicities of PAHs with α-endosulfan were determined in Eisenia fetida adults using an artificial soil system. α-Endosulfan and five PAHs were tested for their acute toxicity toward E. fetida in artificial soils. Only α-endosulfan, fluorene, and phenanthrene showed acute toxicities, with LC values of 9.7, 133.2, and 86.2 mg kg, respectively. A mixture toxicity assay was conducted using α-endosulfan at LC and fluorene or phenanthrene at LC in the artificial soils. Upon exposure to the mixture of fluorene and α-endosulfan, earthworms were killed in increasing numbers owing to their synergistic effects, while no other mixture showed any additional toxicity toward the earthworms. Along with the acute toxicity results, the biochemical and molecular changes in the fluorene- and phenanthrene-treated earthworms with or without α-endosulfan treatment demonstrated that enhancement of glutathione S-transferase activity was dependent on the addition of PAH chemicals, and the HSP70 gene expression increased with the addition of α-endosulfan. Taken together, these findings contribute toward understanding the adverse effects of pollutants when present separately or in combination with other types of chemicals.
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http://dx.doi.org/10.1007/s10653-016-9876-3DOI Listing
April 2017
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