• 제목/요약/키워드: cardiovascular toxicity

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Vascular Cell Responses against Oxidative Stress and its Application

  • Ryoo, Sung-Woo;Lee, Sang-Ki;Kim, Cuk-Seong;Jeon, Byeong-Hwa
    • International Journal of Vascular Biomedical Engineering
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    • v.2 no.2
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    • pp.1-9
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    • 2004
  • The history of studies in biology regarding reactive oxygen species (ROS) is approximately 40 years. During the initial 30 years, it appeared that these studies were mainly focused on the toxicity of ROS. However, recent studies have identified another action regarding oxidative signaling, other than toxicity of ROS. Basically, it is suggested that ROS are reactive, and degenerate to biomolecules such as DNA and proteins, leading to deterioration of cellular functions as an oxidative stress. On the other hand, recent studies have shown that ROS act as oxidative signaling in cells, resulting in various gene expressions. Recently ROS emerged as critical signaling molecules in cardiovascular research. Several studies over the past decade have shown that physiological effects of vasoactive factors are mediated by these reactive species and, conversely, that altered redox mechanisms are implicated in the occurrence of metabolic and cardiovascular diseases ROS is a collective term often used by scientist to include not only the oxygen radicals($O2^{-{\cdot}},\;{^{\cdot}}OH$), but also some non-radical derivatives of oxygen. These include hydrogen peroxide, hypochlorous acid (HOCl) and ozone (O3). The superoxide anion ($O2^{-{\cdot}}$) is formed by the univalent reduction of triplet-state molecular oxygen ($^3O_2$). Superoxide dismutase (SOD)s convert superoxide enzymically into hydrogen peroxide. In biological tissues superoxide can also be converted nonenzymically into the nonradical species hydrogen peroxide and singlet oxygen ($^1O_2$). In the presence of reduced transition metals (e.g., ferrous or cuprous ions), hydrogen peroxide can be converted into the highly reactive hydroxyl radical (${^{\cdot}}OH$). Alternatively, hydrogen peroxide may be converted into water by the enzymes catalase or glutathione peroxidase. In the glutathione peroxidase reaction glutathione is oxidized to glutathione disulfide, which can be converted back to glutathione by glutathione reductase in an NADPH-consuming process.

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Generation of Reactive Oxygen Species Contributes to the Development of Carbon Black Cytotoxicity to Vascular Cells

  • Lee, Jong-Gwan;Noh, Won-Jun;Kim, Hwa;Lee, Moo-Yeol
    • Toxicological Research
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    • v.27 no.3
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    • pp.161-166
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    • 2011
  • Carbon black, a particulate form of pure elemental carbon, is an industrial chemical with the high potential of occupational exposure. Although the relationship between exposure to particulate matters (PM) and cardiovascular diseases is well established, the cardiovascular risk of carbon black has not been characterized clearly. In this study, the cytotoxicity of carbon black to vascular smooth muscle and endothelial cells were examined to investigate the potential vascular toxicity of carbon black. Carbon black with distinct particle size, N330 (primary size, 28~36 nm) and N990 (250~350 nm) were treated to A-10, rat aortic smooth muscle cells and human umbilical vein endothelial cell line, ECV304, and cell viability was assessed by lactate dehydrogenase (LDH) leakage assay. Treatment of carbon black N990 resulted in the significant reduction of viability in A-10 cells at 100 ${\mu}g$/ml, the highest concentration tested, while N330 failed to cause cell death. Cytotoxicity to ECV304 cells was induced only by N330 at higher concentration, 200 ${\mu}g$/ml, suggesting that ECV304 cells were relatively resistant to carbon black. Treatment of 100 ${\mu}g$/ml N990 led to the elevation of reactive oxygen species (ROS) detected by dichlorodihydrofluorescein (DCF) in A-10 cells. Pretreatment of antioxidants, N-acetylcysteine (NAC) and sulforaphane restored decreased viability of N990-treated A-10 cells, and N-acetylcysteine, but not sulforaphane, attenuated N990-induced ROS generation in A-10 cells. Taken together, present study shows that carbon black is cytotoxic to vascular cells, and the generation of reactive oxygen contributes to the development of cytotoxicity. ROS scavenging antioxidant could be a potential strategy to attenuate the toxicity induced by carbon black exposure.

Histopathological Evaluation of Heart Toxicity of a Novel Selective PPAR-γ Agonists CKD-501 in db/db Mice

  • Yang, Hyun-Il;Kim, Woo Sik;Kim, Dal-Hyun;Kang, Jin Seok
    • Biomolecules & Therapeutics
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    • v.21 no.1
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    • pp.84-88
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    • 2013
  • High risk of cardiovascular diseases caused by existing PPAR-${\gamma}$ agonists such as rosiglitazone and pioglitazone has been recently reported. CKD-501 is a novel selective PPAR-${\gamma}$ agonist as a potential target to reduce cardiovascular risk in non-insulin dependent diabetes mellitus (NIDDM). In this study, We investigated potential cardiotoxicity of CKD-501 and compared its toxicity with that of rosiglitazone or pioglitazone using db/db mice. After 12-week repeated administration of CKD-501 at doses of 3, 10 and 30 mg/kg/day or rosiglitazone at doses of 10 and 30 mg/kg/day or pioglitazone at doses of 200 and 540 mg/kg/day, animals were sacrificed for investigation of potential toxicities. Diameters of left ventricles and areas of cardiomyocytes were measured. And lipid accumulation and apoptosis in heart muscle were examined by oil red O staining and TUNEL staining, respectively. Diameters of left ventricles were significantly increased in high dose treatment group of pioglitazone compared to control (p<0.05), while other groups showed a tendency for an increase. All test articles induced significantly the increase of area of cardiomyocytes in heart compared to control (p<0.01), in regular order as pioglitazone > CKD-501 ${\geq}$ rosiglitazone. However, lipid accumulation and apoptotic changes in heart were not observed in all dosing groups. Taken together, the myocardial cell hypertrophy of CKD-501 are relatively lower than that of pioglitazone and similar to rosiglitazone. And it is suggested that the myocardial cell hypertrophy of CKD-501 are less adverse in clinical use for the management of the NIDDM.

Biodistribution of Inhaled Titania ($TiO_2$) Nanoparticles in Rats (백서에서 흡인된 티타니아 나노입자의 생체 내 분포에 관한 연구)

  • Choi, Se-Hoon;Park, Kay-Hyun;Jheon, San-Hhoon;Kim, Joo-Hyun;Chung, Jin-Haeng;Cho, So-Hye;Park, Jong-Ku;Kim, Tae-Heon
    • Korean Journal of Bronchoesophagology
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    • v.16 no.1
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    • pp.33-38
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    • 2010
  • Titania nanomaterials are widely used as cosmetics and dyes, however the impacts on human health are uncertain, We investigated the biodistribution of inhaled titania nanoparticles in rats, Methods Eight weeks-old SD rats were intubated and inhaled with 3 mg titania nanoparticles, twice a week, for 2 weeks, After inhalation, the rats were sacrificed and tissues or heart, lung. intestine, brain, and liver were obtained, We investigated the tissues with optical microscope (OM), transmission electron microscope (EM), scanning EM, And to analyze titania concentration of each tissue, we lysed the tissues with radioimmunoprecipitation assay (RlPA) lysis buffer or acid. Results Granulation tissues in lung were confirmed on the optical microscope, however the other organs had no abnormalities in OM images, In EM images, the rats which inhaled titania nanoparticles showed calcium deposition at heart, brain, and intestine, Titania concentration in lung was increased on the inhaled rat sacrificed I month after last exposure. Conclusion Inhaled titania nanoparticles is thought to be deposited and make inflammatory reaction in lung, and the deposition was not efficiently cleared over a month. However inhaled titania nanoparticles may rarely pass through the alveolus-blood barrier and distribute to other organs of the bod.

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Cyclosporine-Assoc iated Central Neurotox ic its after Hearat Transplantat ion 1 Case Report (심장이식 환자에서 Cyclosporine에 의한 중추신경독성 -1례 보고-)

  • Kim, Young-Hee;Song, Hyun;Song, Meong-Gun
    • Journal of Chest Surgery
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    • v.30 no.11
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    • pp.1136-1138
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    • 1997
  • A 45-year-old man underwent heart transplantation due to dilated cardiomyopathy. Cyclosporine, 2 mg/kg per day, was intravenously givell postoperatively. As central neurotoxicity signs that were included pin-point pupil, no light reflex, coma, were presented at 8 postoperative hours, cyclosporine was decreased to 1 mg/kg er day. At that time the cyclosporine level was 345 $\mu\textrm{g}$/L, the serum creatinine level was 1.8mg/dl and the serum magnesium level was within normal limit. He awaked at 31 postoperative hours and all sign of cyclosporine-induced central neurotoxicity was resolved after postoperative days. He was discharged without sequale at postoperative day 28.

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Experimental Study of Ginkgo-Chunghyul-dan on Anti-oxidant, Anti-platelet Aggregation, and Anti-hyperlipidemic Activity

  • Yun, Sang-Pil;Bae, Hyung-Sup;Park, Seong-Uk;Jung, Woo-Sang;Moon, Sang-Kwan;Park, Jung-Mi;Ko, Chang-Nam;Cho, Ki-Ho;Kim, Young-Suk
    • The Journal of Korean Medicine
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    • v.29 no.5
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    • pp.52-66
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    • 2008
  • Objectives :Ginkgo-Chunghyul-dan (GCHD) is newly developed herbal medicine to prevent and treat stroke. In this study, we investigated whether the GCHD had antioxidant activity and anti-platelet aggregation effect in vitro and hypolipidemic activities in vivo. Methods :Anti-oxidant activity of GCHD was measured using the Blois method, anti-platelet effect of GCHD was assessed by the Born method, and hypolipidemic activities of GCHD were evaluated in corn oil- or Triton WR-1339-induced and cholesterol-fed rats. Results :GCHD showed anti-oxidant activity in the study inhibiting the formation of 1-diphenyl-2-picrylhydrazyl radicals and xanthine oxidase activity. GCHD had anti-platelet aggregation activity. GCHD significantly lowered total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) in high cholesterol diet and Triton WR-1339 induced model TG in corn oil-induced model. GCHD had no acute toxicity at a single dosage. Conclusion : These results suggest that GCHD has the potential to treat hyperlipidemia and stroke.

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Environmental Mercury and Its Toxic Effects

  • Rice, Kevin M.;Walker, Ernest M. Jr.;Wu, Miaozong;Gillette, Chris;Blough, Eric R.
    • Journal of Preventive Medicine and Public Health
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    • v.47 no.2
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    • pp.74-83
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    • 2014
  • Mercury exists naturally and as a man-made contaminant. The release of processed mercury can lead to a progressive increase in the amount of atmospheric mercury, which enters the atmospheric-soil-water distribution cycles where it can remain in circulation for years. Mercury poisoning is the result of exposure to mercury or mercury compounds resulting in various toxic effects depend on its chemical form and route of exposure. The major route of human exposure to methylmercury (MeHg) is largely through eating contaminated fish, seafood, and wildlife which have been exposed to mercury through ingestion of contaminated lower organisms. MeHg toxicity is associated with nervous system damage in adults and impaired neurological development in infants and children. Ingested mercury may undergo bioaccumulation leading to progressive increases in body burdens. This review addresses the systemic pathophysiology of individual organ systems associated with mercury poisoning. Mercury has profound cellular, cardiovascular, hematological, pulmonary, renal, immunological, neurological, endocrine, reproductive, and embryonic toxicological effects.

Clinical Assessment on the Safety of Chunghyul-dan (Qingwie-dan) (청혈단(淸血丹)의 임상적인 부작용에 대한 연구)

  • 조기호;정우상;박성욱;문상관;김영석;배형섭
    • The Journal of Korean Medicine
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    • v.24 no.3
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    • pp.45-50
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    • 2003
  • Background and Purpose : Chunghyul-dan has been widely used in the Department of Cardiovascular & Neurologic Diseases, Kyung Hee Oriental Medical Center to prevent stroke by lowering serum cholesterol level. Previous experimental and clinical studies revealed that Chunghyul-dan had therapeutic effects on hyperlipidemia by inhibiting HMG-CoA reductase and pancreatic lipase. It was also reported that Chunghyul-dan showed an anti-oxidation effect by scavenging free radicals and inhibiting nitric oxide synthesis. Therefore, we examined the safety of Chunghyul-dan on all subjects who had been treated with it. Methods : We performed a retrospective study by reviewing the medical records of those who had been administrated Chunghyul-dan at Kyung Hee Oriental Medical Center from February 8,2001 to December 31,2002. The subjects' general characteristics (gender, age, medical history, and present illness), recorded adverse effects, and the results of laboratory findings were obtained and analyzed to assess the clinical safety of Chunghyul-dan. Results : Six hundred fifty six subjects were treated with Chunghyul-dan. Clinical adverse effects appeared in 13 subjects, the major symptom being indigestion (8 subjects). The apparent frequency of adverse effects was much lower than that in previous reports on the safety of certain medications. On investigation of laboratory findings, we could not find any hepatic or renal toxicity. Conclusion : We suggest that our results contribute towards confirming the safety of Chunghyul-dan by offering clinical evidence.

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Potential Health Risks from Persistent Organic Pollutants (POPs) in Marine Ecosystem

  • Lee, Youn Ju;Jang, Jae-Seok;Yang, Jae-Ho
    • Journal of Marine Bioscience and Biotechnology
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    • v.8 no.1
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    • pp.10-17
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    • 2016
  • A wide-spread contamination of persistent organic pollutants (POPs) such as dioxins, PCBs, PBDEs in the aquatic ecosystem has generated a great concern over the potential risk for these substances to impact marine biotas and food web. Since a major exposure route of these substances to the humans is through the consumption of food including fish and marine byproducts, the consumption of contaminated products has been a great public health concern. Exposure to POPs has been associated with a wide spectrum of adverse effects including reproductive, developmental, immunologic, carcinogenic, and neurotoxic effects. This review covers the background information of key POPs substances and the recent development of toxicity studies including the mode of action. Because neurotoxic effects of some POPs have been observed in humans at low concentrations, polychlorinated biphenyl (PCB), a representative chemical of POPs, is focused to discuss the possible mode(s) of action for the neurotoxic effects. This review provides the updates of toxicity studies on POPs and paves ways to discuss a possible implication of contaminated marine biota over the human health among the marine biotechnology researchers.

Chronic Exposure to Arsenic and the Effects on Human Health (비소 만성 노출의 건강영향에 대한 고찰)

  • Jung-Yeon Kwon;Young-Seoub Hong
    • Journal of Environmental Health Sciences
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    • v.49 no.5
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    • pp.237-246
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    • 2023
  • Background: Arsenic is a metalloid of public health significance due to its unique material properties and toxicity and the widespread pollution in the environment. Arsenic exists as inorganic arsenic and organic arsenic with distinct chemical properties. Its toxicity varies depending on the properties. Objectives: Although the carcinogenicity of arsenic has been identified, the various diseases that occur after acute and chronic exposure to arsenic are not yet clearly known. Methods: Research on the effects of chronic exposure to arsenic on human health was searched and the results were summarized. Results: It has been found that cancer occurs due to exposure to high concentrations of arsenic in areas with elevated exposure to arsenic, but research results have recently been presented on health effects caused by chronic exposure to low concentrations of arsenic. Cancers have also been identified to be related to inorganic arsenic, including skin cancer, lung cancer, and bladder cancer. Significant relationships with neurological diseases, cardiovascular diseases, and diabetes mellitus have been suggested as well. Conclusions: Our results suggest that it is necessary to evaluate the health impact on residents around abandoned metal mines and industrial complexes in South Korea.