• Title/Summary/Keyword: immune toxicity

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28days Repeat Oral Dose Toxicity Test of 'Hyeonggaeyeongyotang' extract in SD Rats (형개련교탕(荊芥連翹湯) 추출물(抽出物)의 SD Rats에서 28일 경구(經口) 반복투여 독성시험)

  • An, Hyun-Jue;Hwang, Sun-Yi;Lee, Jong-Rok;Kim, Sang-Chan;Jee, Seon-Young
    • Herbal Formula Science
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    • v.16 no.1
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    • pp.147-168
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    • 2008
  • HYTE (Hyeonggaeyeongyotang Extract), a polyherbal formula has been used as folk medicine, 28days repeat oral dose toxicity was tested in SD rats according to KFDA Guideline[2005-60]. Methods : In this study, mortality, clinical signs, body weight and gains, food and water consumption, ophthalmologic observation, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathological observations were conducted during 28days of dosing periods. Results: 1. No HYTE treatment-related mortalities and clinical signs were detected in all dosing levels tested in male and female rats during the whole experimental periods. 2. No HYTE treatment-related changes on body weight, gains and food consumption were detected in all dosing levels tested in male and female rats during the whole experimental periods except for 2000mg/kg-dosing female groups in which significantly increase of body weight, gains, food and water consumption were detected compared to that of vehicle control in some points. 3. No HYTE treatment-related changes on ophthalmologic examination were detected in all dosing levels tested in male and female rats. 4. No HYTE treatment-related changes on urinalysis were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing female groups in which, significantly increase of urine volume and related decrease on the urine specific gravity were detected as secondary effects of increase on the water consumptions not HYTE treatment-related toxicological signs. 5. No HYTE treatment-related changes on hematology were detected in all dosing levels tested in male and female rats except for increases in the total WBC count and lymphocytes of 2000mg/kg-dosing male and female groups with decrease of large unstained cells as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. 6. No HYTE treatment-related changes on serum biochemistry were detected in all dosing levels tested in male and female rats. 7. No HYTE treatment-related changes on gross findings, organ weight and histopathology were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing male and female groups in which, spleen and thymus organ weights, hypertrophy at gross observation and hyperpalsia of lymphoid cells and follicles at histopathological observation in spleen and thymus were detected as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. Conclusions : Based on these results, the NOAEL and MTD of HYTE in SD rats were considered as over 2000mg/kg, respectively at 28days repeat oral dose toxicity test because most of these findings were considered as results of pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs or secondary effects.

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Experimental Research on the Effect of Haeyeol-tang (해열탕(解熱湯)의 항염증(抗炎症), 항산화(抗酸化), 항노화(抗老化) 작용(作用)에 대한 실험적(實驗的) 연구(硏究))

  • Chu, Cheng-Kang;Kim, Jin-Ju;Roh, Young-Lae;Lee, Sung-Hun;Jeong, Seung-Yeon;Jung, Hee-Jae;Jung, Sung-Ki
    • The Journal of Internal Korean Medicine
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    • v.28 no.4
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    • pp.671-680
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    • 2007
  • Objectives : The purpose of this study was to examine the effect of Haeyeol-tang on infectious disease of respiratory system. Methods : Haeyeol-tang was used by cold storage after dilution with 1, 10 and $100{\mu}g/ml$ of PBS, from dried material as extracted material with extraction with 50% ethanol. Statistical significance was examined through measuring TNF-$\alpha$, RT-PCR, DPPH, nitric oxide(NO), and MTT of Raw264.7 cells activated with LPS. Results : For the toxicity experiment of Haeyeol-tang, almost no toxicity was shown on cells in the concentration ranges of 1, 10 and $100{\mu}g/ml$. For the effect of NO production, Haeyeol-tang showed significant (p<0.001) decrease of NO production, according to its concentration. For the effect on the eliminating activity of DPPH radical, Haeyeol-tang showed increasing tendency of eliminating activity of DPPH radical, according to its concentration. For the effect on revelation of NOS2 enzyme, Haeyeol-tang showed inhibiting tendency against the revelation of NOS2, according to its concentration. For the effect on the TNF-$\alpha$ production, Haeyeol-tang showed significant (p<0.001) decrease of TNF-$\alpha$ production. Conclusions : This result means that Haeyeol-tang is effective for anti-inflammation, as well as excellent effect for anti-oxidation and anti-aging.

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Immune inflammatory modulation as a potential therapeutic strategy of stem cell therapy for ALS and neurodegenerative diseases

  • Kim, Seung Hyun;Oh, Ki-Wook;Jin, Hee Kyung;Bae, Jae-Sung
    • BMB Reports
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    • v.51 no.11
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    • pp.545-546
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    • 2018
  • With emerging evidence on the importance of non-cell autonomous toxicity in neurodegenerative diseases, therapeutic strategies targeting modulation of key immune cells. including microglia and Treg cells, have been designed for treatment of ALS and other neurodegenerative diseases. Strategy switching the patient's environment from a pro-inflammatory toxic to an anti-inflammatory, and neuroprotective condition, could be potential therapy for neurodegenerative diseases. Mesenchymal stem cells (MSCs) regulate innate and adaptive immune cells, through release of soluble factors such as $TGF-{\beta}$ and elevation of regulatory T cells (Tregs) and T helper-2 cells (Th2 cells), would play important roles, in the neuroprotective effect on motor neuronal cell death mechanisms in ALS. Single cycle of repeated intrathecal injections of BM-MSCs demonstrated a clinical benefit lasting at least 6 months, with safety, in ALS patients. Cytokine profiles of CSF provided evidence that BM-MSCs, have a role in switching from pro-inflammatory to anti-inflammatory conditions. Inverse correlation of $TGF-{\beta}1$ and MCP-1 levels, could be a potential biomarker to responsiveness. Thus, additional cycles of BM-MSC treatment are required, to confirm long-term efficacy and safety.

Biological Safety and B Cells Activation Effects of Stephania delavayi Diels

  • Park, Dae-Hun;Li, Yong-Chun;Shim, Jae-Gal;Xu, Hong-De;Li, Lan;Lee, Min-Jae;Kwon, Myung-Sang
    • Molecular & Cellular Toxicology
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    • v.5 no.1
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    • pp.93-98
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    • 2009
  • Stephania delavayi Diels. has been used as an immune activator or an anti-inflammatory drug in China. We examined the immune modulation effect and 7-days repeated-dose toxicity to validate its biological safety and efficiency. Mice were repeatedly administrated with 50 mg/kg S. delavayi Diels. daily by I.P for 7 days. S. delavayi Diels. induced B cell activation but had no effect on other immune cells such as T cell, natural killer (NK) cell, and macrophage ($M{\varphi}$). S. delavayi Diels.-treated group exhibited no statistical significance from the control group in physical conditions; body weight, complete blood count (CBC), serum biochemical indexes etc. There was no difference between the control group and S. delavayi Diels.-treated group in gross findings such as histopathological alteration. In conclusion, S. delavayi Diels. is safe above the dose of immune modulation.

Oxidative stress and non-specific immune responses in juvenile black sea bream, Acanthopagrus schlegelii, exposed to waterborne zinc

  • Kim, Jun-Hwan;Park, Hee-Ju;Kim, Kyeong-Wook;Kang, Ju-Chan
    • Fisheries and Aquatic Sciences
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    • v.20 no.6
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    • pp.11.1-11.8
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    • 2017
  • Juvenile black sea bream, Acanthopagrus schlegelii, were exposed to waterborne zinc (Zn) at concentrations of 0, 200, and $400{\mu}g/L$, at temperatures of 18 or $26^{\circ}C$ for 4 weeks. Superoxide dismutase (SOD) activities in the liver and gill of A. schlegelii significantly increased following exposure to waterborne Zn. Significant reduction in glutathione S-transferase (GST) activity in the liver and gill was observed following exposure to waterborne Zn. Glutathione (GSH) concentrations in the liver and gill also significantly decreased following exposure to waterborne Zn. Phagocytosis and lysozyme in the plasma and kidney were significantly increased following exposure to waterborne Zn. High water temperature increased alterations in the antioxidant and immune responses. The results of the present study suggest that waterborne Zn induced significant alterations in oxidative stress, increased immune responses and high temperature that trigger Zn toxicity.

Toxic Effects on the Nonspecific Immune System of the Rock Bream Oplegnathus fasciatus upon Exposure to Di-2-ethylhexyl Phthalate

  • Kim, Jun-Hwan;Jeong, Dal-Sang;Kang, Ju-Chan
    • Fisheries and Aquatic Sciences
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    • v.16 no.3
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    • pp.171-176
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    • 2013
  • The aim of this study was to investigate the in vivo toxicity of di-2-ethylhexyl phthalate (DEHP), on the immune system of the rock bream, Oplegnathus fasciatus. Fish were injected twice intraperitoneally with DEHP (200, 400, and 800 mg/kg BW), and the cellularity and functional activity of phagocytes in the spleen and head kidney were measured. The number of head kidney leukocyte cells was significantly greater in fish treated with 800-mg DEHP/kg BW. Nonspecific immunity, as determined by the phagocytic index, was significantly decreased at 800-mg DEHP/kg BW in the head kidney. A significant reduction in phagocytic capacity was observed in the head kidney at ${\geq}$400-mg DEHP/kg BW. Furthermore, significantly increased levels of serum glutamic oxaloacetate transaminase and glutamic pyruvate transaminase indicated a marked hepatic dysfunction in immunosuppressed fish. Total serum protein was significantly reduced at ${\geq}$400-mg DEHP/kg BW; however, there were no significant changes in lysozyme activity. These results demonstrate that immune responses in the rock bream, Oplegnathus fasciatus can predict immunotoxicity at doses ${\geq}$400-mg DEHP/kg BW.

DNA Microarrays Analysis of Gene Expression Profiles in Diabetes-related genes using Immunosuppressant (면역억제제에 의한 당뇨 관련 유전자의 DNA microarray 분석)

  • Kim, Kyoung-Shin;Kim, Byoung-Soo
    • Journal of Haehwa Medicine
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    • v.21 no.1
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    • pp.11-21
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    • 2012
  • New onset diabetes is a major complication after kidney transplantation. However, the natural course of posttransplantation diabetes mellitus (PTDM) remains unclear. The aim of this study was to demonstrate the detailed natural courses of PTDM according to the onset and persistency of hyperglycemia, and to investigate risk factors for development of different courses of PTDM in renal allograft recipients. The purpose of this study is to develop novel immune suppressants for PTDM using of action mechanism of them. The use of immunosuppressive drugs in transplanted patients is associated with the development of diabetes, possibly due to ${\beta}$-cell toxicity. To better understand the mechanisms leading to post-transplant diabetes, we investigated the actions of prolonged exposure of ${\beta}$-cells to therapeutical levels of tacrolimus (FK506) or cyclosporin A(CsA). The immunosuppressive drug cyclosporine(CsA) is a potent agent widely used after organ transplantations and various autoimmune disorders. After using CsA, some patients suffer severe complications including renal and vascular toxicity. The renal or vascular toxicity is influenced by the degree of the endothelial damage. FK506(tacrolimus) is a widely used immunosuppressive agent in the treatment of various medical conditions, including autoimmune disease, bone marrow and organ transplantations. We found some interesting clusters and confirmed the feasibility of cDNA microarray in the study of Immunosuppressant. In this study, we investigated gene expression patterns induced by Immunosuppressant in RIN-m5F of rat insulinoma cell line. Gene expressions evaluated using cDNA microarry in two clusters were increased or decreased. this study provides comprehensive comparison of the patterns of gene expression changes induced by CsA and FK506 in ${\beta}$-cells. This study could establish that the mode of action mechanism by which currently used insulin inhibitors inducing PTDM could be elucidated at least in part, which raises the possibility that novel immune suppressive PTDM can be developed. The molecular biological study on PTDM will also contribute the progress in diabetes research field as well as in that of PTDM.

Simple Evaluation of Listeria monocytogenes Pathogenesis Using Caenorhabditis elegans Animal Model

  • Yang, Kyoung Hee;Yun, Bohyun;Choi, Hye Jin;Ryu, Sangdon;Lee, Woong Ji;Oh, Mi-Hwa;Song, Min-Ho;Kim, Jong Nam;Oh, Sangnam;Kim, Younghoon;Kim, Young Jun
    • Food Science of Animal Resources
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    • v.39 no.1
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    • pp.84-92
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    • 2019
  • Listeria monocytogenes is a major cause of serious foodborne illness in the dairy foods. Although Caenorhabditis elegans model is well established as a virulence model of pathogenic bacteria, its application on L. monocytogenes is critically unclear. The objective of this study was to carry out an evaluation of L. monocytogenes toxicity using C. elegans nematode as a simple host model. We found that C. elegans nematodes have high susceptibility to L. monocytogenes infection, as a consequence of accumulation of bacteria in the worms' intestine. However, L. innocua, which is known to be non-toxic, is not accumulate in the intestine of worms and is not toxic similarly to Escherichia coli OP50 known as the normal feed source of C. elegans. Importantly, immune-associated genes of C. elegans were intensely upregulated more than 3.0-fold when they exposed to L. monocytogenes. In conclusion, we established that C. elegans is an effective model for studying the toxicity of L. monocytogenes and we anticipate that this system will result in the discovery of many potential anti-listeria agents for dairy foods.

Study on the modulation of immune system of CPS in atopic dermatitis induced animal models (외치방인 청기패독산(淸肌敗毒散)의 아토피피부염 동물 병태 모델에서의 면역조절작용에 관한 연구)

  • Lee, Youn-Jeong;Gim, Seon-Bin;Choi, Hak-Joo;Lee, Ki-Moo;Kim, Dong-Hee
    • Journal of Haehwa Medicine
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    • v.20 no.2
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    • pp.1-16
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    • 2012
  • In order to study the effect of CPS in the treatment of atopic dermatitis (AD), its role on various immune related cytokines were tested. Levels of liver and kidney function markers such as ALT, AST, BUN in NC/Nga mice were all normal indicating no toxicity in CPS treated group. Significant recovery from AD could be observed in CPS treated group through naked eye observation. Dermatitis index was significantly decreased after 11, 12, and 13 weeks of treatment. CD4+, CD8+, CD3+ /CD69+ immune cell ratio in DLN were decreased significantly by 37.2%, 49%, 20.8% in CPS treated group. CD4+ and CD11b+ /Gr-1+ immune cell ratio in dorsal skin were decreased significantly by 50.8% and 59.2% in CPS treated group. Expression of IL-4, IL-5, IL-6, IL-13 and TNF-${\alpha}$ in spleen were decreased by 78.8%, 97.8%, 64.7%, 73.6%, and 68.4%, respectively in CPS treated group. The results above strongly indicated the significant immune modulatory effect of CPS and thus clinical application of CPS on AD treatment.

Theoretical Approach for Physicochemical Factors Affecting Human Toxicity of Dioxins (다이옥신의 인체 독성에 영향을 미치는 물리화학적 인자에 대한 이론적 접근)

  • 황인철;박형석
    • Environmental Analysis Health and Toxicology
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    • v.14 no.1_2
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    • pp.65-73
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    • 1999
  • Dioxins refer to a family of chemicals comprising 75 polychlorinated dibenzo-p-dioxin (PCDD) and 135 polychlorinated dibenzo-p-furan (PCDF) congeners, which may cause skin disorder, human immune system disruption, birth defects, severe hormonal imbalance, and cancer. The effects of exposure of dioxin-like compounds such as PCBs are mediated by binding to the aryl hydrocarbon receptor (AHR), which is a ligand-activated transcription factor. To grasp physicochemical factors affecting human toxicity of dioxins, six geometrical and topological indices, eleven thermodynamic variables, and quantum mechanical descriptors including ESP (electrostatic potential) were analyzed using QSAR and semi-empirical AM1 method. Planar dioxins with high lipophilicity and large surface tension show the probability that negative electrostatic potential in the lateral oxygen may make hydrogen bonding with DNA bases to be a carcinogen.

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