Preeyaporn Koedrith | Mahidol University (original) (raw)

Papers by Preeyaporn Koedrith

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Abstract: Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel a... more Abstract: Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system’s ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repai...

Heavy metals cadmium has been used as a yellow pigment due to its bright and lasting color. Consi... more Heavy metals cadmium has been used as a yellow pigment due to its bright and lasting color. Considering the toxicity of cadmium, yellow iron oxide has been suggested as a substitute due to its cost-effectiveness. However, cellular and molecular safety information of yellow iron oxide is not fully understood. Metal-mediated cellular stress indicated by metallothionein 1 expression were measured by western blotting and qRT-PCR in cadmium- or iron oxide-treated HepG2 cells. Genotoxicity were detected using comet assay and micronuclei assay in HepG2 cells and rat liver tissue. Observed toxicological effects were quantified and scored on a scale bar for integrated analysis. Yellow iron oxide showed significantly low metallothionein 1 expression and genotoxicity in all results. This result indicates high potential of iron oxide as an alternative to cadmium. We demonstrated the comparative toxicity of the cadmium and yellow iron oxide in terms of stress-responsive biomarker expression and ...

Nickel is known as a carcinogen through the environmental and occupational exposures. One of carc... more Nickel is known as a carcinogen through the environmental and occupational exposures. One of carcinogenic mechanisms of nickel is an induction of oxidative stresses and inhibition of DNA repair. But the exact molecular mechanisms by which nickel induces carcinogenicity remains unclear. We selected the sub-lethal dose of nickel in human cells using MTT assay and FACS analysis. To demonstrate the effect of nickel on transcriptional activity of p53, we conducted an electrophoretic mobility shift assay and streptavidin magnetic bead assay. Gadd45a–APE1 complex was confirmed by in situ proximity ligation assay. We demonstrated that nickel can interfere with the physical interaction between Gadd45a and APE1, in vitro and in situ, as well as APE1 activity in vitro. Our study implies that the inhibition of p53-mediated APE1 activity in base excision repair might be suggested as one of the potential carcinogenic mechanisms in response to nickel even at a low dose.

Journal of Cancer Prevention

Based on epidemiological studies, an International Agency for Research on Cancer Working Group de... more Based on epidemiological studies, an International Agency for Research on Cancer Working Group determined that strong inorganic acid mists containing sulfuric acid are carcinogenic to human even though, sulfuric acid, per se, is not. Accumulative studies indicate that there is a link between chronic occupational exposure to sulfuric acid mists and an increased risk of laryngeal cancer. Unintended, acute exposure to sulfuric acid mists can cause corrosive damage to target tissues depending on the route of exposure. This review compares the toxicity and carcinogenicity of sulfuric acid mists compared to other strong inorganic acid mists. It also examines the routes and duration of exposure (short-term, prolonged, and long-term). In vivo evidence does not support or refute the carcinogenicity of sulfuric inorganic mists even though its co-carcinogenic or promoting potential has been considered. On the basis of existing evidence on sulfuric acid mist toxicity, we suggested a putative adverse outcome pathway (AOP) relevant to carcinogenicity caused by mists containing sulfuric acid. A possible key factor involved in sulfuric acid mist carcinogenesis is the genotoxic effects of low pH since it can increase instability in chromosomes and DNA. A putative AOP for sulfuric acid mist carcinogenicity would help generate better risk assessments and more accurate predictions regarding the risk of developing cancer due to prolonged exposure. Establishing an AOP would also be useful for future studies examining the carcinogenicity of other strong inorganic mists.

Molecular & Cellular Toxicology

BackgroundsTrends in the use of an anticoagulant as a dispersing stabilizer are addressed. An eff... more BackgroundsTrends in the use of an anticoagulant as a dispersing stabilizer are addressed. An effective approach to preparing stable nanosized titanium dioxide (nTiO2) for accurate and systematic assessment of nano- toxicity has not been established.MethodsAmong the dispersants tested here, it was found that sodium polyacrylate (PAA) was the most effective dispersant for nTiO2 in culture media. Our study was the first to demonstrate that a stable PAA-dispersed nTiO2 (nTiO2/PAA) suspension showed more toxic than nTiO2 without PAA in human HaCaT keratinocytes.ResultsInitially, MTT results showed that the stable nTiO2/PAA dispersion exhibited significantly greater cytotoxicity than nTiO2 without PAA. In addition, the stable nTiO2/PAA dispersion induced markedly more oxidative stress than nTiO2 without PAA. Importantly, the stable nTiO2/PAA dispersion caused DNA breakage to a greater extent than nTiO2 without PAA.ConclusionOur findings indicated that the anti-coagulant PAA is suitable for preparing homologous dispersed nTiO2 under realistic physiological culture test conditions.

Parasitology

SUMMARY At present, there are no medicinal plant extracts currently available for treatment and c... more SUMMARY At present, there are no medicinal plant extracts currently available for treatment and control of fasciolosis. The present work could provide, for the first study, conclusions on the in vitro fasciolicidal properties of the ethanol extract of Terminalia catappa L. (TcCE) leaves against adult Fasciola gigantica after incubation with RPMI-1640 medium containing the TcCE at various concentrations and times when compared with triclabendazole (TCZ). The relative motility and survival index values of the TcCE-treated flukes decreased at a more rapid rate than the TCZ-treated flukes. The death of the parasites was observed after exposed to TcCE at 3 h incubation with 400, 800 and 1000 µg mL−1, and at 6 h incubation in 100 and 200 µg mL−1. Vacuolization, blebbings and partial disruption on the parasites’ tegument were observed by light microscopy. When examined by scanning electron microscopy, TcCE caused similar tegumental alterations in the parasites as those observed in TCZ trea...

Environmental science and pollution research international, Jan 20, 2017

Cadmium is a toxic metallic element that poses serious human health risks via consumption of cont... more Cadmium is a toxic metallic element that poses serious human health risks via consumption of contaminated agricultural products. The effect of mixtures of dicalcium phosphate and organic amendments, namely cow manure (MD) and leonardite (LD), on Cd and Zn uptake of three rice cultivars (KDML105, KD53, and PSL2) was examined in mesocosm experiments. Plant growth, Cd and Zn accumulation, and physicochemical properties of the test soils were investigated before and after plant harvest. Amendment application was found to improve soil physicochemical properties; in particular, soil organic matter content and nutrient (N, P, K, Ca, and Mg) concentrations increased significantly. The MD treatment was optimal in terms of increasing plant growth; the MD and LD treatments decreased soil Cd concentration by 3.3-fold and 1.6-fold, respectively. For all treatments, all rice cultivars accumulated greater quantities of Cd and Zn in roots compared with panicles and shoots. Among the three cultivars...

The Journal of toxicological sciences, 2017

Cadmium contamination still occurs in some parts of the world, and its concentrations in the envi... more Cadmium contamination still occurs in some parts of the world, and its concentrations in the environment are monitored in most countries due to its adverse effects on human health. We herein established yeast (Saccharomyces cerevisiae) reporter assay strains carrying plasmids with the yeast JLP1, SEO1, and CUP1 promoters connected to the bacterial lacZ reporter gene. The strain carrying the high-copy number pESC-JLP1-lacZ reporter plasmid was more responsive to cadmium than strains with other reporter plasmids. This JLP1-lacZ reporter assay strain will be useful for monitoring cadmium contamination in environmental water and soil as a first screening tool preceding official instrumental analyses, because the assay is rapid, easy to handle, and has the ability to process a large number of samples at a low cost.

Toxicology and Environmental Health Sciences, 2016

As public interest in safety has increased the toxicity evaluation of chemicals become more impor... more As public interest in safety has increased the toxicity evaluation of chemicals become more important. In this study, the DNA-damaging effect of genotoxicants was examined in HepG2 cell line originated from human hepatocellular carcinoma by widely used genotoxicity assays: the comet assay and gammaH2AX immunostaining. Four different direct/indirect genotoxicants were tested in dose-/time-dependent manner. The comet assay and the gammaH2AX immunostaining enables detection of DNA damages in the form of DNA strand breaks with different sensitivity. Therefore, the combination of comet assay and gammaH2AX immunostaining will be complementary tool for evaluation of various forms and degree of DNA damage. Our result also suggested that HepG2 cells could be a suitable model for assessing the genotoxicity of various mutagens and for determining the lowest genotoxic concentration. Further analysis using a larger number of chemicals is warranted to determine the sensitivity and the specificity of HepG2 with in vitro genotoxicity test.

Parasitology, 2016

SUMMARYPresently, no effective anthelmintic drugs have been used to treat and control paramphisto... more SUMMARYPresently, no effective anthelmintic drugs have been used to treat and control paramphistomosis, a severe disease of ruminants. In this study, we have investigated thein vitroanthelmintic effect of the leaves ofTerminalia catappaL. crude extract (TcCE) and albendazole (ABZ) on adultFischoederius cobboldiafter incubating the flukes in RPMI-1640 medium containing the TcCE at various doses and times. The TcCE-treated flukes at all dosages exhibited rapid decrease of motility, and the relative motility (RM) values were decreased sharply from start to 3 h. Worms were killed after 6 and 12 h of treatment with 1000, 1500 and 2000µg mL−1as well as 500µg mL−1of TcCE, respectively. By light microscopy examination, the flukes exhibited the earliest alteration in a limited area of the tegument. At scanning electron microscopy level, the flukes’ tegument showed similar sequence of morphological alterations after treatment with ABZ and TcCE that consisted of swelling of ridges and folds, f...

Food-borne pathogens cause infectious diseases in people worldwide. Hence, the development of rap... more Food-borne pathogens cause infectious diseases in people worldwide. Hence, the development of rapid detection methods for food-borne pathogens is necessary. The application of potentially useful nanoparticles (NPs) results in enhanced sensitivity, improved response time, and increased portability owing to their distinct chemical and optical features. The widely used NPs include quantum dot (QD) NPs, metal NPs, silica NPs, and magnetic NPs as well as potent intrinsic antimicrobial NPs. The NPs can also act as multivalent scaffolds for supramolecular assemblies since their high surface-tovolume ratio enables the functionalization of unique spatial domains, allowing their versatile implementation in various sensing schemes. In this review, we focus on the developments and analytical applications of NPs in chemical and biological sensing within foods and crop matrices. We also discuss advanced tools of NP-based sensitive assays, key requirements, and shortcomings.

International journal of molecular sciences, Jan 29, 2015

Due to the rapid advent in genomics technologies and attention to ecological risk assessment, the... more Due to the rapid advent in genomics technologies and attention to ecological risk assessment, the term "ecotoxicogenomics" has recently emerged to describe integration of omics studies (i.e., transcriptomics, proteomics, metabolomics, and epigenomics) into ecotoxicological fields. Ecotoxicogenomics is defined as study of an entire set of genes or proteins expression in ecological organisms to provide insight on environmental toxicity, offering benefit in ecological risk assessment. Indeed, Daphnia is a model species to study aquatic environmental toxicity designated in the Organization for Economic Co-operation and Development's toxicity test guideline and to investigate expression patterns using ecotoxicology-oriented genomics tools. Our main purpose is to demonstrate the potential utility of gene expression profiling in ecotoxicology by identifying novel biomarkers and relevant modes of toxicity in Daphnia magna. These approaches enable us to address adverse phenotyp...

Cancer Research, 2014

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Thioredoxin-1 (Trx1) is an ... more Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Thioredoxin-1 (Trx1) is an antioxidant enzyme with a protective role in the removal of reactive oxygen species (ROS). We investigated the mechanism by which the redox modulator Trx1 affects base excision repair (BER) activity to understand the protective role of Trx1. We constructed a Trx1 knockdown system to demonstrate the specific mechanism of Trx1. DNA damage in terms of relative intensity of the DNA tail and γ-H2AX foci was markedly higher in the Trx1 shRNA cells compared with that in the wild type cells, leading to increased cellular susceptibility to a sublethal dose of BER-inducible toxicant, nitrosomethylurea (NMU). In addition, we observed a modulatory role of Trx1 in the BER pathway via the p53 downstream gene, growth arrest, and DNA-damage-inducible protein 45 α (Gadd45a). The protein level and function of p53, a Trx1 downstream gene, coincidently decreased in the Trx1 shRNA cells. Furthermore, Trx1 shRNA cells showed decreased Gadd45a expression and interaction of Gadd45a with apurynic/apyrimidinic endonuclease 1 (APE1) as well as APE1 activity. In conclusion, Trx1 might cooperate in the control of APE1 function by modulating the p53-mediated BER via the protein-protein interaction between Gadd45a and APE1, providing insight into the novel role of redox factor Trx1 in modulation of BER. Note: This abstract was not presented at the meeting. Citation Format: Hye Lim Kim, Preeyaporn Koedrith, Sang Min Lee, Yeo Jin Kim, Young Rok Seo. Protective role of thioredoxin-1 in base excision repair under redox modulation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2419. doi:10.1158/1538-7445.AM2014-2419

Experimental and therapeutic medicine, Sep 1, 2011

Thioredoxin reductase 1 (Trr1) is an antioxidant and redox regulator that functions in governing ... more Thioredoxin reductase 1 (Trr1) is an antioxidant and redox regulator that functions in governing the cellular redox state and survival against oxidative insults in mammals. However, this selenoprotein is also overexpressed in various forms of malignant cancers, leading to the hypothesis that Trr1 may be a potential target for cancer therapy. A quinone anti-cancer drug, mitomycin C (MMC), has been clinically used in the treatment of several types of tumors, including those of the colon. MMC exerts its activity via ROS induction and further results in DNA cross-linkage. To evaluate the significant role of Trr1 in MMC resistance in human colon cancer (RKO) cells, specific reduction in the expression of Trr1 was achieved using short-hairpin RNA (shRNA)-based interference. Our results showed that stable Trr1 shRNA knockdown manifested higher cellular susceptibility to MMC in comparison to that in wild-type cells. In addition, increased intracellular ROS accumulation appeared in the Trr1 ...

Molecular & Cellular Toxicology, 2014

International Journal of Nanomedicine, 2014

Engineered nanoparticles (NPs) are widely used in many sectors, such as food, medicine, military,... more Engineered nanoparticles (NPs) are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed.

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2013

Thioredoxin-1 (Trx1) is an antioxidant enzyme with a protective role in the removal of oxidative ... more Thioredoxin-1 (Trx1) is an antioxidant enzyme with a protective role in the removal of oxidative stress. We investigated the mechanism by which the redox modulator Trx1 affects base excision repair (BER) activity to understand the protective role of Trx1. We constructed a Trx1 knockdown system to demonstrate the specific mechanism of Trx1. DNA damage in terms of relative intensity of the DNA tail and ␥-H2AX foci was markedly higher in the Trx1 shRNA cells compared with that in the wild type cells, leading to increased cellular susceptibility to a sublethal dose of BER-inducible toxicant, nitrosomethylurea (NMU). In addition, we observed a modulatory role of Trx1 in the BER pathway via the p53 downstream gene, growth arrest, and DNA-damage-inducible protein 45 ␣ (Gadd45a). The protein level and function of p53, a Trx1 downstream gene, coincidently decreased in the Trx1 shRNA cells. Furthermore, Trx1 shRNA cells showed decreased Gadd45a expression and interaction of Gadd45a with apurinic/apyrimidinic endonuclease 1 (APE1) as well as APE1 activity. In conclusion, Trx1 might cooperate in the control of APE1 function by modulating the p53-mediated BER via the protein-protein interaction between Gadd45a and APE1, providing insight into the novel role of redox factor Trx1 in modulation of BER.

Molecular & Cellular Toxicology, 2012

Cadmium is well known as a ubiquitous environmental contaminant with high levels of toxicity. Cad... more Cadmium is well known as a ubiquitous environmental contaminant with high levels of toxicity. Cadmium exposure is associated with various types of cancers in humans, and its mechanism is not yet well known. However, generation of reactive oxygen species (ROS) is often linked with the detrimental effects of cadmium. Thioredoxin reductase 1 (TrxR1) is a member of the thioredoxin system, which plays important roles in maintaining redox homeostasis in cells. In this study, we investigated the role of TrxR1 in protection against cadmium-induced oxidative stress and genotoxicity. To ensure a relevant concentration of heavy metals resembling that in the environment was used, all experiments were performed with a sublethal concentration of cadmium, which did not induce cytotoxicity or alter the cell cycle in RKO cells. We observed a significant increase in DNA damage in terms of γ-H2AX foci and DNA strand breaks as well as intracellular ROS generation under cadmium exposure in TrxR1 siRNA-treated RKO cells in comparison to wild type. Furthermore, to examine whether or not TrxR1 is responsible for protection from cadmiuminduced carcinogenicity, we investigated the frequency of cadmium-induced micronuclei (MN), which is one of the criteria for identifying genotoxicity and carcinogenicity. Our results show that TrxR1 knock-down RKO cells had remarkably higher frequency of MN compared to wild type cells. Taken together, these results imply that TrxR1 might play an important role in the cellular defense system against cadmium-induced carcinogenicity via suppression of oxidative stressinduced DNA damage.

International Journal of Molecular Sciences, 2011

Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classif... more Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system's ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repair systems. Interaction of non-enzymatic antioxidants (carotenoids, flavonoids, glutathione, selenium, vitamin C, vitamin E, and others) with cellular oxidative stress markers (catalase, glutathione peroxidase, and superoxide dismutase) as well as certain regulatory factors, including AP-1, NF-κB, Ref-1, and p53 is also reviewed. Dysregulation of protective pathways, including cellular antioxidant network against free radicals as well as DNA repair deficiency is related to oncogenic stimulation. These observations provide evidence that emerging oxidative

R e v I e w open access to scientific and medical research Open Access Full Text Article

Abstract: Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel a... more Abstract: Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system’s ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repai...

Heavy metals cadmium has been used as a yellow pigment due to its bright and lasting color. Consi... more Heavy metals cadmium has been used as a yellow pigment due to its bright and lasting color. Considering the toxicity of cadmium, yellow iron oxide has been suggested as a substitute due to its cost-effectiveness. However, cellular and molecular safety information of yellow iron oxide is not fully understood. Metal-mediated cellular stress indicated by metallothionein 1 expression were measured by western blotting and qRT-PCR in cadmium- or iron oxide-treated HepG2 cells. Genotoxicity were detected using comet assay and micronuclei assay in HepG2 cells and rat liver tissue. Observed toxicological effects were quantified and scored on a scale bar for integrated analysis. Yellow iron oxide showed significantly low metallothionein 1 expression and genotoxicity in all results. This result indicates high potential of iron oxide as an alternative to cadmium. We demonstrated the comparative toxicity of the cadmium and yellow iron oxide in terms of stress-responsive biomarker expression and ...

Nickel is known as a carcinogen through the environmental and occupational exposures. One of carc... more Nickel is known as a carcinogen through the environmental and occupational exposures. One of carcinogenic mechanisms of nickel is an induction of oxidative stresses and inhibition of DNA repair. But the exact molecular mechanisms by which nickel induces carcinogenicity remains unclear. We selected the sub-lethal dose of nickel in human cells using MTT assay and FACS analysis. To demonstrate the effect of nickel on transcriptional activity of p53, we conducted an electrophoretic mobility shift assay and streptavidin magnetic bead assay. Gadd45a–APE1 complex was confirmed by in situ proximity ligation assay. We demonstrated that nickel can interfere with the physical interaction between Gadd45a and APE1, in vitro and in situ, as well as APE1 activity in vitro. Our study implies that the inhibition of p53-mediated APE1 activity in base excision repair might be suggested as one of the potential carcinogenic mechanisms in response to nickel even at a low dose.

Journal of Cancer Prevention

Based on epidemiological studies, an International Agency for Research on Cancer Working Group de... more Based on epidemiological studies, an International Agency for Research on Cancer Working Group determined that strong inorganic acid mists containing sulfuric acid are carcinogenic to human even though, sulfuric acid, per se, is not. Accumulative studies indicate that there is a link between chronic occupational exposure to sulfuric acid mists and an increased risk of laryngeal cancer. Unintended, acute exposure to sulfuric acid mists can cause corrosive damage to target tissues depending on the route of exposure. This review compares the toxicity and carcinogenicity of sulfuric acid mists compared to other strong inorganic acid mists. It also examines the routes and duration of exposure (short-term, prolonged, and long-term). In vivo evidence does not support or refute the carcinogenicity of sulfuric inorganic mists even though its co-carcinogenic or promoting potential has been considered. On the basis of existing evidence on sulfuric acid mist toxicity, we suggested a putative adverse outcome pathway (AOP) relevant to carcinogenicity caused by mists containing sulfuric acid. A possible key factor involved in sulfuric acid mist carcinogenesis is the genotoxic effects of low pH since it can increase instability in chromosomes and DNA. A putative AOP for sulfuric acid mist carcinogenicity would help generate better risk assessments and more accurate predictions regarding the risk of developing cancer due to prolonged exposure. Establishing an AOP would also be useful for future studies examining the carcinogenicity of other strong inorganic mists.

Molecular & Cellular Toxicology

BackgroundsTrends in the use of an anticoagulant as a dispersing stabilizer are addressed. An eff... more BackgroundsTrends in the use of an anticoagulant as a dispersing stabilizer are addressed. An effective approach to preparing stable nanosized titanium dioxide (nTiO2) for accurate and systematic assessment of nano- toxicity has not been established.MethodsAmong the dispersants tested here, it was found that sodium polyacrylate (PAA) was the most effective dispersant for nTiO2 in culture media. Our study was the first to demonstrate that a stable PAA-dispersed nTiO2 (nTiO2/PAA) suspension showed more toxic than nTiO2 without PAA in human HaCaT keratinocytes.ResultsInitially, MTT results showed that the stable nTiO2/PAA dispersion exhibited significantly greater cytotoxicity than nTiO2 without PAA. In addition, the stable nTiO2/PAA dispersion induced markedly more oxidative stress than nTiO2 without PAA. Importantly, the stable nTiO2/PAA dispersion caused DNA breakage to a greater extent than nTiO2 without PAA.ConclusionOur findings indicated that the anti-coagulant PAA is suitable for preparing homologous dispersed nTiO2 under realistic physiological culture test conditions.

Parasitology

SUMMARY At present, there are no medicinal plant extracts currently available for treatment and c... more SUMMARY At present, there are no medicinal plant extracts currently available for treatment and control of fasciolosis. The present work could provide, for the first study, conclusions on the in vitro fasciolicidal properties of the ethanol extract of Terminalia catappa L. (TcCE) leaves against adult Fasciola gigantica after incubation with RPMI-1640 medium containing the TcCE at various concentrations and times when compared with triclabendazole (TCZ). The relative motility and survival index values of the TcCE-treated flukes decreased at a more rapid rate than the TCZ-treated flukes. The death of the parasites was observed after exposed to TcCE at 3 h incubation with 400, 800 and 1000 µg mL−1, and at 6 h incubation in 100 and 200 µg mL−1. Vacuolization, blebbings and partial disruption on the parasites’ tegument were observed by light microscopy. When examined by scanning electron microscopy, TcCE caused similar tegumental alterations in the parasites as those observed in TCZ trea...

Environmental science and pollution research international, Jan 20, 2017

Cadmium is a toxic metallic element that poses serious human health risks via consumption of cont... more Cadmium is a toxic metallic element that poses serious human health risks via consumption of contaminated agricultural products. The effect of mixtures of dicalcium phosphate and organic amendments, namely cow manure (MD) and leonardite (LD), on Cd and Zn uptake of three rice cultivars (KDML105, KD53, and PSL2) was examined in mesocosm experiments. Plant growth, Cd and Zn accumulation, and physicochemical properties of the test soils were investigated before and after plant harvest. Amendment application was found to improve soil physicochemical properties; in particular, soil organic matter content and nutrient (N, P, K, Ca, and Mg) concentrations increased significantly. The MD treatment was optimal in terms of increasing plant growth; the MD and LD treatments decreased soil Cd concentration by 3.3-fold and 1.6-fold, respectively. For all treatments, all rice cultivars accumulated greater quantities of Cd and Zn in roots compared with panicles and shoots. Among the three cultivars...

The Journal of toxicological sciences, 2017

Cadmium contamination still occurs in some parts of the world, and its concentrations in the envi... more Cadmium contamination still occurs in some parts of the world, and its concentrations in the environment are monitored in most countries due to its adverse effects on human health. We herein established yeast (Saccharomyces cerevisiae) reporter assay strains carrying plasmids with the yeast JLP1, SEO1, and CUP1 promoters connected to the bacterial lacZ reporter gene. The strain carrying the high-copy number pESC-JLP1-lacZ reporter plasmid was more responsive to cadmium than strains with other reporter plasmids. This JLP1-lacZ reporter assay strain will be useful for monitoring cadmium contamination in environmental water and soil as a first screening tool preceding official instrumental analyses, because the assay is rapid, easy to handle, and has the ability to process a large number of samples at a low cost.

Toxicology and Environmental Health Sciences, 2016

As public interest in safety has increased the toxicity evaluation of chemicals become more impor... more As public interest in safety has increased the toxicity evaluation of chemicals become more important. In this study, the DNA-damaging effect of genotoxicants was examined in HepG2 cell line originated from human hepatocellular carcinoma by widely used genotoxicity assays: the comet assay and gammaH2AX immunostaining. Four different direct/indirect genotoxicants were tested in dose-/time-dependent manner. The comet assay and the gammaH2AX immunostaining enables detection of DNA damages in the form of DNA strand breaks with different sensitivity. Therefore, the combination of comet assay and gammaH2AX immunostaining will be complementary tool for evaluation of various forms and degree of DNA damage. Our result also suggested that HepG2 cells could be a suitable model for assessing the genotoxicity of various mutagens and for determining the lowest genotoxic concentration. Further analysis using a larger number of chemicals is warranted to determine the sensitivity and the specificity of HepG2 with in vitro genotoxicity test.

Parasitology, 2016

SUMMARYPresently, no effective anthelmintic drugs have been used to treat and control paramphisto... more SUMMARYPresently, no effective anthelmintic drugs have been used to treat and control paramphistomosis, a severe disease of ruminants. In this study, we have investigated thein vitroanthelmintic effect of the leaves ofTerminalia catappaL. crude extract (TcCE) and albendazole (ABZ) on adultFischoederius cobboldiafter incubating the flukes in RPMI-1640 medium containing the TcCE at various doses and times. The TcCE-treated flukes at all dosages exhibited rapid decrease of motility, and the relative motility (RM) values were decreased sharply from start to 3 h. Worms were killed after 6 and 12 h of treatment with 1000, 1500 and 2000µg mL−1as well as 500µg mL−1of TcCE, respectively. By light microscopy examination, the flukes exhibited the earliest alteration in a limited area of the tegument. At scanning electron microscopy level, the flukes’ tegument showed similar sequence of morphological alterations after treatment with ABZ and TcCE that consisted of swelling of ridges and folds, f...

Food-borne pathogens cause infectious diseases in people worldwide. Hence, the development of rap... more Food-borne pathogens cause infectious diseases in people worldwide. Hence, the development of rapid detection methods for food-borne pathogens is necessary. The application of potentially useful nanoparticles (NPs) results in enhanced sensitivity, improved response time, and increased portability owing to their distinct chemical and optical features. The widely used NPs include quantum dot (QD) NPs, metal NPs, silica NPs, and magnetic NPs as well as potent intrinsic antimicrobial NPs. The NPs can also act as multivalent scaffolds for supramolecular assemblies since their high surface-tovolume ratio enables the functionalization of unique spatial domains, allowing their versatile implementation in various sensing schemes. In this review, we focus on the developments and analytical applications of NPs in chemical and biological sensing within foods and crop matrices. We also discuss advanced tools of NP-based sensitive assays, key requirements, and shortcomings.

International journal of molecular sciences, Jan 29, 2015

Due to the rapid advent in genomics technologies and attention to ecological risk assessment, the... more Due to the rapid advent in genomics technologies and attention to ecological risk assessment, the term "ecotoxicogenomics" has recently emerged to describe integration of omics studies (i.e., transcriptomics, proteomics, metabolomics, and epigenomics) into ecotoxicological fields. Ecotoxicogenomics is defined as study of an entire set of genes or proteins expression in ecological organisms to provide insight on environmental toxicity, offering benefit in ecological risk assessment. Indeed, Daphnia is a model species to study aquatic environmental toxicity designated in the Organization for Economic Co-operation and Development's toxicity test guideline and to investigate expression patterns using ecotoxicology-oriented genomics tools. Our main purpose is to demonstrate the potential utility of gene expression profiling in ecotoxicology by identifying novel biomarkers and relevant modes of toxicity in Daphnia magna. These approaches enable us to address adverse phenotyp...

Cancer Research, 2014

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Thioredoxin-1 (Trx1) is an ... more Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Thioredoxin-1 (Trx1) is an antioxidant enzyme with a protective role in the removal of reactive oxygen species (ROS). We investigated the mechanism by which the redox modulator Trx1 affects base excision repair (BER) activity to understand the protective role of Trx1. We constructed a Trx1 knockdown system to demonstrate the specific mechanism of Trx1. DNA damage in terms of relative intensity of the DNA tail and γ-H2AX foci was markedly higher in the Trx1 shRNA cells compared with that in the wild type cells, leading to increased cellular susceptibility to a sublethal dose of BER-inducible toxicant, nitrosomethylurea (NMU). In addition, we observed a modulatory role of Trx1 in the BER pathway via the p53 downstream gene, growth arrest, and DNA-damage-inducible protein 45 α (Gadd45a). The protein level and function of p53, a Trx1 downstream gene, coincidently decreased in the Trx1 shRNA cells. Furthermore, Trx1 shRNA cells showed decreased Gadd45a expression and interaction of Gadd45a with apurynic/apyrimidinic endonuclease 1 (APE1) as well as APE1 activity. In conclusion, Trx1 might cooperate in the control of APE1 function by modulating the p53-mediated BER via the protein-protein interaction between Gadd45a and APE1, providing insight into the novel role of redox factor Trx1 in modulation of BER. Note: This abstract was not presented at the meeting. Citation Format: Hye Lim Kim, Preeyaporn Koedrith, Sang Min Lee, Yeo Jin Kim, Young Rok Seo. Protective role of thioredoxin-1 in base excision repair under redox modulation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2419. doi:10.1158/1538-7445.AM2014-2419

Experimental and therapeutic medicine, Sep 1, 2011

Thioredoxin reductase 1 (Trr1) is an antioxidant and redox regulator that functions in governing ... more Thioredoxin reductase 1 (Trr1) is an antioxidant and redox regulator that functions in governing the cellular redox state and survival against oxidative insults in mammals. However, this selenoprotein is also overexpressed in various forms of malignant cancers, leading to the hypothesis that Trr1 may be a potential target for cancer therapy. A quinone anti-cancer drug, mitomycin C (MMC), has been clinically used in the treatment of several types of tumors, including those of the colon. MMC exerts its activity via ROS induction and further results in DNA cross-linkage. To evaluate the significant role of Trr1 in MMC resistance in human colon cancer (RKO) cells, specific reduction in the expression of Trr1 was achieved using short-hairpin RNA (shRNA)-based interference. Our results showed that stable Trr1 shRNA knockdown manifested higher cellular susceptibility to MMC in comparison to that in wild-type cells. In addition, increased intracellular ROS accumulation appeared in the Trr1 ...

Molecular & Cellular Toxicology, 2014

International Journal of Nanomedicine, 2014

Engineered nanoparticles (NPs) are widely used in many sectors, such as food, medicine, military,... more Engineered nanoparticles (NPs) are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed.

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2013

Thioredoxin-1 (Trx1) is an antioxidant enzyme with a protective role in the removal of oxidative ... more Thioredoxin-1 (Trx1) is an antioxidant enzyme with a protective role in the removal of oxidative stress. We investigated the mechanism by which the redox modulator Trx1 affects base excision repair (BER) activity to understand the protective role of Trx1. We constructed a Trx1 knockdown system to demonstrate the specific mechanism of Trx1. DNA damage in terms of relative intensity of the DNA tail and ␥-H2AX foci was markedly higher in the Trx1 shRNA cells compared with that in the wild type cells, leading to increased cellular susceptibility to a sublethal dose of BER-inducible toxicant, nitrosomethylurea (NMU). In addition, we observed a modulatory role of Trx1 in the BER pathway via the p53 downstream gene, growth arrest, and DNA-damage-inducible protein 45 ␣ (Gadd45a). The protein level and function of p53, a Trx1 downstream gene, coincidently decreased in the Trx1 shRNA cells. Furthermore, Trx1 shRNA cells showed decreased Gadd45a expression and interaction of Gadd45a with apurinic/apyrimidinic endonuclease 1 (APE1) as well as APE1 activity. In conclusion, Trx1 might cooperate in the control of APE1 function by modulating the p53-mediated BER via the protein-protein interaction between Gadd45a and APE1, providing insight into the novel role of redox factor Trx1 in modulation of BER.

Molecular & Cellular Toxicology, 2012

Cadmium is well known as a ubiquitous environmental contaminant with high levels of toxicity. Cad... more Cadmium is well known as a ubiquitous environmental contaminant with high levels of toxicity. Cadmium exposure is associated with various types of cancers in humans, and its mechanism is not yet well known. However, generation of reactive oxygen species (ROS) is often linked with the detrimental effects of cadmium. Thioredoxin reductase 1 (TrxR1) is a member of the thioredoxin system, which plays important roles in maintaining redox homeostasis in cells. In this study, we investigated the role of TrxR1 in protection against cadmium-induced oxidative stress and genotoxicity. To ensure a relevant concentration of heavy metals resembling that in the environment was used, all experiments were performed with a sublethal concentration of cadmium, which did not induce cytotoxicity or alter the cell cycle in RKO cells. We observed a significant increase in DNA damage in terms of γ-H2AX foci and DNA strand breaks as well as intracellular ROS generation under cadmium exposure in TrxR1 siRNA-treated RKO cells in comparison to wild type. Furthermore, to examine whether or not TrxR1 is responsible for protection from cadmiuminduced carcinogenicity, we investigated the frequency of cadmium-induced micronuclei (MN), which is one of the criteria for identifying genotoxicity and carcinogenicity. Our results show that TrxR1 knock-down RKO cells had remarkably higher frequency of MN compared to wild type cells. Taken together, these results imply that TrxR1 might play an important role in the cellular defense system against cadmium-induced carcinogenicity via suppression of oxidative stressinduced DNA damage.

International Journal of Molecular Sciences, 2011

Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classif... more Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system's ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repair systems. Interaction of non-enzymatic antioxidants (carotenoids, flavonoids, glutathione, selenium, vitamin C, vitamin E, and others) with cellular oxidative stress markers (catalase, glutathione peroxidase, and superoxide dismutase) as well as certain regulatory factors, including AP-1, NF-κB, Ref-1, and p53 is also reviewed. Dysregulation of protective pathways, including cellular antioxidant network against free radicals as well as DNA repair deficiency is related to oncogenic stimulation. These observations provide evidence that emerging oxidative