• Environmental Analysis Health and Toxicology
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• 제21권1호
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• pp.1-11
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• 2006

Arsenic is a ubiquitous element found in several forms in environment. Although certain foods, such as marine fish, contain substantial levels of organic arsenic forms, they are relatively low in toxicity compared to inorganic forms. In contrast, arsenic in drinking water is predominantly inorganic and very toxic. Chronic ingestion of arsenic-contaminated drinking water is therefore the major pathway posing potential risk to human health. World populations are exposed to low to moderate levels of arsenic of parts per billion (ppb) to thousands of ppb. When exposed to human, it could metabolize into monomethylarsonous acid ($MMA^{III}$) and dimethylarsinous acid ($DMA^{III}$) which are highly toxic. Lots of stuides have been recently focused how $MMA^{III}\;and\;DMA^{III}$ induce toxic insults in various target tissues. Epidemiological studies revealed that chronic arsenic exposure caused cancer, cardiovascular diseases, and diabetes etc. In this review, the current understanding of arsenic on health effects will be discussed.

• Journal of Breast Disease
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• 제6권2호
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• pp.39-45
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• 2018

Purpose: Dieckol, a phlorotannin compound isolated from Ecklonia cava, has been reported to have antioxidant, antiviral, anti-inflammatory, and anticancer properties. The purpose of this study was to investigate its anticancer effects on human breast cancer cell lines. Methods: In this study, the viability of two human breast cancer cell lines SK-BR-3 and MCF-7 was investigated after dieckol treatment using a WST-1 assay. Apoptosis and cell cycle distribution were assayed via Annexin V-fluorescein isothiocyanate and propidium iodide staining followed by flow cytometric analysis. Immunoblotting analysis was also performed using Bax/Bcl-2 to determine whether the dieckol-induced apoptosis was mediated by the intrinsic apoptotic pathway. Results: In a dose dependent manner, dieckol reduced the number of viable cells and increased the number of apoptotic cells. The effect of dieckol on the cell cycle distribution was analyzed using flow cytometry. Dieckol treatment significantly increased the percentage of MCF-7 and SK-BR-3 in the G2/M phase. Immunoblot analysis revealed that 24 hours of dieckol exposure increased the Bax/Bcl-2 ratio. Conclusion: Dieckol induced cytotoxicity in MCF-7 and SK-BR-3 human breast cancer cells inducing apoptosis and cell cycle arrest. Therefore, it is suggested that dieckol may be a potential therapeutic agent for breast cancer.

• Advances in Traditional Medicine
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• 제10권4호
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• pp.254-262
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• 2010

Artemisia capillaris (A. capillaries) is known to play roles in many cellular events, such as cell proliferation, differentiation, and apoptosis. We investigated the antifibrogenic efficacy of A. capillaris in the immortalized human hepatic stellate cell line LX2. Cell proliferation was determined by the MTT assay. Cell cycle was analyzed by the flow cytometry. Apoptotic cells were measured using a cell death detection ELISA. Caspase activity was detected by a colorimetric assay. The mRNA level of Bcl-2 and Bax mRNA were measured by real-time PCR. MEK and ERK protein were detected by Western blot analysis. We provide evidence that A. capillaris induces cell cycle arrest, apoptosis, and potently inhibits the mitogen-activated protein kinase pathway. A. capillaris inhibited cell proliferation of LX2 cells in a dose- and time-dependent manner, increased the apoptosis fraction at cell cycle analysis with an accompanying DNA fragmentation, and resulted in a significant decrease in Bcl-2 mRNA levels and an increase in Bax expression. Exposure of LX2 cells to A. capillaris induced caspase-3 activation, but co-treatment of A. capillaris with the pan-caspase inhibitor Z-VAD-FMK, and the caspase-3 inhibitor Z-DEVE-FMK, blocked apoptosis. A. capillaris down-regulated Mcl-1 protein levels and inhibited phosphorylation of MEK/ERK, suggesting that it mediates cell death in LX2 cells through the down-regulation of Mcl-1 protein via a MEK/ERK-independent pathway.

• Molecular & Cellular Toxicology
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• 제1권2호
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• pp.73-77
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• 2005

Nickel is the one of potent environmental, the occupational pollutants and the classified human carcinogens. It is a serious hazard to human health, when the metal exposure. To prevent human diseases from the heavy metals, it is seemingly important that understanding of how nickel exerts their toxicity and carcinogenic effect at a molecular and a genomic level. The process of nickel absorption has been demonstrated as phagocytosis, iron channel and diffusion. Uptaked nickel has been suggested to induce carcinogenesis via two pathways, a direct DNA damaging pathway and an indirect DNA damaging pathway. The former was originated from the ability of metal to generate Reactive Oxygen Species (ROS) and the reactive intermediates to interact with DNA directly. Ni-generated ROS or Nickel itself, interacts with DNAs and histones to cause DNA damage and chromosomal abnormality. The latter was originated from an indirect DNA damage via inhibition of DNA repair, or condensation and methylation of DNA. Cells have ability to protect from the genotoxic stresses by changing gene expression. Microarray analysis of the cells treated with nickel or nickel compounds, show the specific altered gene expression profile. For example, HIF-I (Hypoxia-Inducible Factor I) and p53 were well known as transcription factors, which are upregulated in response to stress and activated by both soluble and insoluble nickel compounds. The induction of these important transcription factors exert potent selective pressure and leading to cell transformation. Genes of metallothionein and family of heat shock proteins which have been known to play role in protection and damage control, were also induced by nickel treatment. These gene expressions may give us a clue to understand of the carcinogenesis mechanism of nickel. Further discussions on molecular and genomic, are need in order to understand the specific mechanism of nickel toxicity and carcinogenicity.

• 자원환경지질
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• 제38권5호
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• pp.535-545
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• 2005

본 연구에서는 폐금속광산 지역에서의 비소가 인체에 미치는 위해영향을 정량적으로 평가하기 위하여 동일, 옥동, 동정, 도곡 및 화천광산 주변 지역에서 광미, 토양, 농작물 및 지하수를 채취하여 화학분석을 실시하였다. 이들 폐금속광산 주변에 폐기된 광미내 비소 함량은 매우 높게 나타났으며, 이러한 광미가 바람이나 강우에 의해 광미댐 하부에 있는 농경지나 하천으로 유입되어 주변 환경을 오염시킬 가능성이 크므로 이들 토양, 농작물, 자연수 시료들에 대한 화학분석자료를 바탕으로 인체위해성평가 모델링을 실시하였다. 폐금속광산 지역에서의 인체노출경로는 농사활동을 통한 토양의 섭취, 지하수(식수)의 섭취, 쌀의 섭취, 농사활동에 의한 토양의 피부접촉, 목욕에 의한 지하수의 피부접촉 등 5가지로 파악할 수 있었다. 각 노출경로별 비발암성위해도 평가 결과, 모든 광산에서 지하수를 식수로 섭취하는 노출경로와 쌀의 섭취를 통해 비소의 독성위해도가 가장 높은 것으로 나타났다. 특히, 동일광산과 옥동광산에서는 HI지수가 7.0 이상으로, 화천광산의 경우는 5.0 이상으로 매우 높게 나타나 이들 지역 주민들의 비소의 독성위해성이 높았다. 비소에 대한 발암위해도 평가 결과, 동일광산, 옥동광산 및 화천광산 지역의 쌀 섭취의 노출경로를 통한 비소에 의해 암이 발생할 확률은 만명중의 5명에서 8명 정도로 높게 나타났다. 지하수를 식수로 섭취하는 경우, 비소의 발암위해도도 이들 광산지역에서 만명중의 1명보다 높게 나타났다. 이는 미국 EPA에서 제시한 초과발암위해도보다도 크므로 이들 지역 주민들이 비소에 의해 오염된 농작물(쌀)이나 지하수를 식수로 지속적으로 장기간 섭취하게 된다면 비소가 건강에 미치는 위해영향이 크다고 판단된다.warfarin 용량 조절에 유용할 것으로 생각된다.대한 치료 순응도가 높아졌다. 후 동율동 전환율이나 좌심방 수축능 회복에 좋은 결과를 보여주었다 그러나 향후 대상환자들에 대한 중장기적인 추적 관찰이 필요하리라 생각한다.pm1.6$일째에 관상동맥조영술을 시행하여 모든 도관의 개존율$(100\%=57/57)$을 확인하였다 수술 전 중재 술을 시행한 1개소에서는 중재술 부위의 재협착소견이 보여 수술 후 조영술시 재풍선확장술로 치료하였다. 수술 후 추적관찰(평균 $25\pm26$개월)동안 1예에서 심부전으로 사망하였다. 생존한 환자 24예에서 술 후 평균 $9.6\pm3$개월째에 관상동맥조영술을 시행하였고 이식도관이 string 징후를 보인 1예를 제외하고 모두 개존(56/57)되어 있었으며, 약물용출형 스탠트를 시행하기 이전의 12예의 중재술 중 2예에서 $50\%$ 이상의 스텐트 협착이 있었으나 흉통의 재발은 없었다. 결론: 하이브리드 관상동맥 우회 술은 수술위험도를 낮추기 위하여 최소절개 관상동맥우회술과 병합하여 시도될 수 있을 뿐 아니라, 선택적 환자들에서는 정중 흉골절개 관상동맥우회술과 병합하여 수술관련 유병률을 낮추고 심근의 완전 재관류화를 도모할 수 있었다.호도에서 가장 적절한 방법으로 사료된다.비위생 점수가 유의적으로 높은 점수를 나타내었다. 조리종사자의 위생지식 점수와 위생관리 수행수준의 상관관계를 조사한 결과, 위생지식의 기기설비위생은 위생관리 수행수준의 합계(p<0.01)에서 유의적인 상관관계(p<0.01)를 나타내었으며, 위생지식의 식중독 및 미생물은 위생관리 수행수준의 개인위생(p<0.01)과 유의적인

• 한국토양비료학회지
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• 제44권1호
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• pp.38-47
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• 2011

This study focused on health risk assessment via multi-routes of As exposure to establish a target cleanup level (TCL) in abandoned mines. Soil, ground water, and rice samples were collected near ten abandoned mines in November 2009. The As contaminations measured in all samples were used for determining the probabilistic health risk by Monte-Carlo simulation techniques. The human exposure to As compound was attributed to ground water ingestion. Cancer risk probability (R) via ground water and rice intake exceeded the acceptable risk range of $10^{-6}{\sim}10^{-4}$ in all selected mines. In particular, the MB mine showed the higher R value than other mines. The non-carcinogenic effects, estimated by comparing the average As exposure with corresponding reference dose were determined by hazard quotient (HQ) values, which were less than 1.0 via ground water and rice intake in SD, NS, and MB mines. This implied that the non-carcinogenic toxic effects, due to this exposure pathway had a greater possibility to occur than those in other mines. Besides, hazard index (HI) values, representing overall toxic effects by summed the HQ values were also greater than 1.0 in SD, NS, JA, and IA mines. This revealed that non-carcinogenic toxic effects were generally occurred. The As contaminants in all selected mines exceeded the TCL values for target cancer risk ($10^{-6}$) through ground water ingestion and rice intake. However, the As level in soil was greater than TCL value for target cancer risk via inadvertent soil ingestion pathway, except for KK mine. In TCL values for target hazard quotient (THQ), the As contaminants in soil did not exceed such TCL value. On the contrary, the As levels in ground water and polished rice in SD, NS, IA, and MB mines were also beyond the TCL values via ground water and rice intake. This study concluded that the health risks through ground water and rice intake were greater than those though soil inadvertent ingestion and dermal contact. In addition, it suggests that the abandoned mines to exceed the risk-based TCL values are carefully necessary to monitor for soil remediation.

• The Korean Journal of Physiology and Pharmacology
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• 제18권1호
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• pp.25-32
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• 2014

Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory responses. NO is produced by nitric oxide synthase (NOS), and NOS is abundantly expressed in the human dental pulp cells (HDPCs). NO produced by NOS can be cytotoxic at higher concentrations to HDPCs. However, the mechanism by which this cytotoxic pathway is activated in cells exposed to NO is not known. The purpose of this study was to elucidate the NO-induced cytotoxic mechanism in HDPCs. Sodium nitroprusside (SNP), a NO donor, reduced the viability of HDPCs in a dose- and time-dependent manner. We investigated the in vitro effects of nitric oxide on apoptosis of cultured HDPCs. Cells showed typical apoptotic morphology after exposure to SNP. Besides, the number of Annexin V positive cells was increased among the SNP-treated HDPCs. SNP enhanced the production of reactive oxygen species (ROS), and N-acetylcysteine (NAC) ameliorated the decrement of cell viability induced by SNP. However, a soluble guanylate cyclase inhibitor (ODQ) did not inhibited the decrement of cell viability induced by SNP. SNP increased cytochrome c release from the mitochondria to the cytosol and the ratio of Bax/Bcl-2 expression levels. Moreover, SNP-treated HDPCs elevated activities of caspase-3 and caspase-9. While pretreatment with inhibitors of caspase (z-VAD-fmk, z-DEVD-fmk) reversed the NO-induced apoptosis of HDPCs. From these results, it can be suggested that NO induces apoptosis of HDPCs through the mitochondria-dependent pathway mediated by ROS and Bcl-2 family, but not by the cyclic GMP pathway.

• Journal of Ginseng Research
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• 제47권1호
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• pp.65-73
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• 2023

Background: Age-related macular degeneration (AMD) is a significant visual disease that induces impaired vision and irreversible blindness in the elderly. However, the effects of ginseng berry extract (GBE) on the retina have not been studied. Therefore, this study aimed to investigate the protective effects of GBE on blue light (BL)-induced retinal damage and elucidate its underlying mechanisms in human retinal pigment epithelial cells (ARPE-19 cells) and Balb/c retina. Methods: To investigate the effects and underlying mechanisms of GBE on retinal damage in vitro, we performed cell viability assay, pre-and post-treatment of sample, reactive oxygen species (ROS) assay, quantitative real-time PCR (qRT-PCR), and western immunoblotting using A2E-laden ARPE-19 cells with BL exposure. In addition, Balb/c mice were irradiated with BL to induce retinal degeneration and orally administrated with GBE (50, 100, 200 mg/kg). Using the harvested retina, we performed histological analysis (thickness of retinal layers), qRT-PCR, and western immunoblotting to elucidate the effects and mechanisms of GBE against retinal damage in vivo. Results: GBE significantly inhibited BL-induced cell damage in ARPE-19 cells by activating the SIRT1/PGC-1α pathway, regulating NF-kB translocation, caspase 3 activation, PARP cleavage, expressions of apoptosis-related factors (BAX/BCL-2, LC3-II, and p62), and ROS production. Furthermore, GBE prevented BL-induced retinal degeneration by restoring the thickness of retinal layers and suppressed inflammation and apoptosis via regulation of NF-kB and SIRT1/PGC-1α pathway, cleavage of caspase 3 and PARP, and expressions of apoptosis-related factors in vivo. Conclusions: GBE could be a potential agent to prevent dry AMD and progression to wet AMD.

• Journal of Korean Dental Science
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• 제10권1호
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• pp.1-9
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• 2017

There is increasing evidence that the environmental hormones may adversely affect the human body. The human reproductive system misrecognizes some of these endocrine disruptors with consequences to reproductive cell differentiation. Therefore, studies on the safety of these substances have been widely carried out to develop the science to create effective legislation to limit or prevent their use or require the development of inert, alternative substances. A few studies have reported that the oral cavity is the pathway for absorption of these substances released from plastic products or environmental hormone substances. This review suggests that the oral environment is vulnerable to exposure to environmental hormones and introduces supporting literature.

• 대한의생명과학회지
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• 제29권4호
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• pp.287-295
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• 2023

Amifostine was developed to protect cells, but it is known to induce cytotoxicity and apoptosis, and the exact mechanism is unknown. In this study, we investigated how the DNA mismatch repair (MMR) system interacts with p53 to prevent apoptosis, cell cycle arrest, and cytoprotective effects induced by amifostine. HCT116 colon cancer cells sublines HCT116/p53+,HCT116/p53+, HCT116/p53-, HCT116/E6 and HCT116+ch3/E6 cells were used for evaluation. Amifostine induced G1 arrest and increased toxicity two-fold in p53- cells regardless of MMR expression. Both G1 cell cycle arrest and induction of p53 protein peaked at 24 h after the start of amifostine exposure. Both G1 cell cycle arrest and induction of p53 protein peaked at 24 h after the start of amifostine exposure. Amifostine induced the expression of p21 protein in both p53+ and p53- cells. As for apoptosis, compared to p53- cells, p53+ cells showed 3.5~4.2 times resistance to amifostine-induced apoptosis. HCT116+E6 with both p53 and MMR loss showed maximum apoptosis at 48 h, and HCT116+ch3/E6HCT116+ch3/E6 with p53 loss showed maximum apoptosis at 24 h. As a result, it was confirmed through in vitro experiments that amifostine-induced G1 cell cycle arrest and apoptosis are mediated through a pathway dependent on MMR and p53 protein.