• 한국환경보건학회지
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• 제33권2호
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• pp.123-131
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• 2007

Many environmental contaminants including several metals, polycyclic aromatic hydrocarbons, and pharmaceuticals, have been identified to be phototoxic in the water environment. Concerns regarding photo-enhancement of toxicity of several environmental contaminants have been increasing because of the increased level of ultraviolet irradiation on the earth surface. However, there exist arguments that there might be certain defense mechanisms taking place in the aquatic ecosystem, which may include behavioral characteristics or genetic acclimation. This study was conducted to understand the potential responses of aquatic receptors to several phototoxic metals in the real environment, where long-term acclimation of such organisms to low dose UV-B may take place. For this purpose, water flea Daphnia magna was acclimated to environmentally relevant dose of UV-B (12 to $18uW/cm^2$) for >11 generations. The differences in developmental and life history characteristics, and toxicity responses were evaluated. Acclimation did not affect the daphnids' growth, longevity, and reproduction characteristics such as time to first brood, and brood size: After 21 d, survival of D. magna was not influenced by UV-B acclimation. When the number of young per female was compared. the daphnids acclimated for 11 generations tend to produce less number of neonates than the un-acclimated individuals but with no statistical significance (p>0.05). Four metals that were reported to be phototoxic elsewhere were employed in this evaluation, that include As, Cd. Cu, and Ni. UV-B level being applied in acclimation did increase the toxicity of Cd and Cu, significantly (p<0.05). However, the toxicities of As and Ni were not affected by irradiation of UV-B. Phototoxic responses were evaluated between the acclimated and the un-acclimated daphnids. For Cu, UV-B acclimation led to reduction of the photo-induced toxicity $(p\approx0.1)$ in daphnids. Non-acclimated Daphnia were affected by 50% at 4.18 ug/l Cu. but UV-B acclimated individuals exhibited $EC_{50}$ of 5.89 ug/l. With Cd, UV-B acclimation appeared to increase phototoxicity (p>0.05). With As and Ni, UV-B acclimation did not influence photo-induced toxicity. This observation may be in part explained by the type of reactive oxygen species that were generated by each metal. Similar to UV-B light, Cu is known to generate superoxide anion by acting as redox cycling toxicant. This is one of the first studies that employed_laboratory based UV-B acclimated test species for photoenhanced toxicity evaluation.

• 대한약침학회지
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• 제19권4호
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• pp.319-328
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• 2016

Objectives: Advancements in nanotechnology have led to nanoparticle (NP) use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos (Danio rerio). Methods: Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED). For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf ) for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. Results: The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH) during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Conclusion: Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and exposure times used in this study. The embryonic zebrafish model is recommended as a well-established method for rapidly assessing the toxicity of homeopathic drugs.

• Toxicological Research
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• 제17권1호
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• pp.17-25
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• 2001

Korean ginseng products have been fumigated with ethylene oxide (EO) for sterilization and prolongation of storage periods. However, there had been controversies indicating that consumption of EO treated foods might cause harmful effects in human. In Korea, the use EO gas for sterilization of food was banned in 1991. Since then, irradiation technique has been developed as an alternative. This study was carried out to evaluate the safety of irradiated ginseng on peri- and postnatal developmental toxicity in rats. Either EO gas fumigated or gamma-irradiated ginseng was administered to pregnant Wistar rats by oral gavage from gestational day 16 to postnatal day 21. The amount of irradiation used in this study was 5, 10 and 30 kGy, respectively. There were no treatment related changes of dams in deaths, clinical signs, and parturition. No treatment related changes in food consumption, body/organ weight and lactation of dams were observed. Also, no F1 fetuses in external abnormality, physical development, reflex/sensory junctions and behavioral development were found. The results of this study showed that gamma-irradiated ginseng, up to 30 kGy, has no adverse effects on the peri- and postnatal development of rats.

• 생명과학회지
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• 제11권5호
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• pp.447-456
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• 2001

임신랫드에서 fluoroquinolone 항균제 DW-116에 의해 유발된 발생독성이 모동물의 사료섭취량 감소에 의한 영양 결핍이 주요 원인인지 아니면 DW-116이 배.태자에 직접적으로 작용하여 유발된것인지를 조사하고자 시험물질을 랫드에 임신 6일에서 16일까지 0 및 500 mg/kg 용량으로 반복 경구투여하였다. 사료제한군은 시험물질 투여군의 모동물의 섭취한 동일한 양의 사료를 제한급여하였다. 모든모동물을 임신 20일째에 제왕절개하였고, 모독성 및 발생독성을 평가하였다. 시험물질 투여군에서는 독성증상과 체중의 감소, 투여 및 투여후 기간의 체중증가 억제, 사료섭취량의 감소를 포함하는 모독성이 부형제대조군및 사료제한군에 비해 현저하게 증가하였다. 또한, 태자사망의 증가, 생존태자의 감소, 태자체중과 태반중량의 감소, 태자기형의 증가 및 골환지연을 포함하는 발생독성도 현저하게 증가하였다. 반면, 사료제한군에서는 모체 및 태자에서 경미한 독성고견만 인정되었고, 태자사망이나 태자기형 등의 심각한 발생독성은 관찰되지 않았다. 결론적으로 시험물질투여군에서 관찰된 발생독성은 사료섭취량의 감소에 의한 모체의 영양결핍에 기인된 것이 아니라 DW-116의 투여에 기인된 직접효과인 것으로 판단된다.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.289.2-290
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• 2002

Choi group reported that Kamijadowhan (KMD). an oriental herbal medicine, has anti-angiogenic effects and it may be a potential agent for clinical chemoprevention since it inhibits angiogenesis. Objectives of this experiment are to investigate acute, genetic and reproductive/developmental toxicities of KMD preparations. Acute toxicity was performed after single administration of KMO (200-500 mg/kg) to mice. Supravital staining micronucleus assay was conducted using peripheral reticulocytes in mice. (omitted)

• Toxicological Research
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• 제33권2호
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• pp.107-118
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• 2017

Although alternative test methods based on the 3Rs (Replacement, Reduction, Refinement) are being developed to replace animal testing in reproductive and developmental toxicology, they are still in an early stage. Consequently, we aimed to develop alternative test methods in male animals using mouse spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and optimized the in vitro comet assay in our previous study. This study aimed to verify the validity of in vitro tests involving mSSCs by comparing their results with those of in vivo tests using C57BL/6 mice by gavage. We selected hydroxyurea (HU), which is known to chemically induce male reproductive toxicity. The 50% inhibitory concentration ($IC_{50}$) value of HU was 0.9 mM, as determined by the MTT assay. In the in vitro comet assay, % tail DNA and Olive tail moment (OTM) after HU administration increased significantly, compared to the control. Annexin V, PI staining and TUNEL assays showed that HU caused apoptosis in mSSCs. In order to compare in vitro tests with in vivo tests, the same substances were administered to male C57BL/6 mice. Reproductive toxicity was observed at 25, 50, 100, and 200 mg/kg/day as measured by clinical measures of reduction in sperm motility and testicular weight. The comet assay, DCFH-DA assay, H&E staining, and TUNEL assay were also performed. The results of the test with C57BL/6 mice were similar to those with mSSCs for HU treatment. Finally, linear regression analysis showed a strong positive correlation between results of in vitro tests and those of in vivo. In conclusion, the present study is the first to demonstrate the effect of HU-induced DNA damage, ROS formation, and apoptosis in mSSCs. Further, the results of the current study suggest that mSSCs could be a useful model to predict male reproductive toxicity.

• 한국발생생물학회지:발생과생식
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• 제26권4호
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• pp.155-163
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• 2022

Human pluripotent stem cells (hPSCs) can give rise to a vast array of differentiated derivatives, which have gained great attention in the field of in vitro toxicity evaluation. We have previously demonstrated that hPSC-derived alveolar epithelial cells (AECs) are phenotypically and functionally similar to primary AECs and could be more biologically relevant alternatives for assessing the potential toxic materials including in fine dust and cigarette smoking. Therefore, in this study, we employed hPSC-AECs to evaluate their responses to exposure of various concentrations of diesel particulate matter (dPM), cigarette smoke extract (CSE) and nicotine for 48 hrs in terms of cell death, inflammation, and oxidative stress. We found that all of these toxic materials significantly upregulated the transcription of pro-inflammatory cytokines such as IL-1α, IL-β, IL-6, and TNF-α. Furthermore, the exposure of dPM (100 ㎍/mL) strongly induced upregulation of genes related with cell death, inflammation, and oxidative stress compared with other concentrations of CSE and nicotine. These results suggest that hPSC-AECs could be a robust in vitro platform to evaluate pulmotoxicity of various air pollutants and harmful chemicals.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제23권6호
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• pp.501-510
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• 2020

Purpose: To develop a probability-based differential diagnosis for pediatric acute liver failure (PALF) based on age and socioeconomic status of the country of origin. Methods: Comprehensive literature search using PubMed, EMBASE, and SCOPUS databases was performed. Children 0-22 years of age who met PALF registry criteria were included. Articles included >10 children, and could not be a case report, review article, or editorial. No language filter was utilized, but an English abstract was required. Etiology of PALF, age of child, and country of origin was extracted from included articles. Results: 32 full text articles were reviewed in detail; 2,982 children were included. The top diagnosis of PALF in developed countries was acetaminophen toxicity (9.24%; 95% CredI 7.99-10.6), whereas in developing countries it was Hepatitis A (28.9%; 95% CredI 26.3-31.7). In developed countries, the leading diagnosis of PALF in children aged <1 year was metabolic disorder (17.2%; 95% CredI 10.3-25.5), whereas in developing countries it was unspecified infection (39.3%; CredI 27.6-51.8). In developed countries, the leading diagnosis in children aged >1 year was Non-A-B-C Hepatitis (8.18%; CredI 5.28-11.7), whereas in developing countries it was Hepatitis A (32.4%; CredI 28.6-36.3). Conclusion: The leading causes of PALF in children aged 0-22 years differ depending on the age and developmental status of their country of origin, suggesting that these factors must be considered in the evaluation of children with PALF.