• Title/Summary/Keyword: in vivo toxicity

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Evaluation of the Genetic Toxicity of Synthetic Chemicals (XV) -In vivo Peripheral Blood Reticulocytes Micronucleus Assay of 17 Synthetic Chemicals in Mice- (합성화학물질들의 유전독성평가(XV) -마우스의 말초혈의 망상적혈구를 이용한 17종 합성화학물질들의 생체내 소핵시험-)

  • Kim Mi-Soon;Kim Youn-Jung;Ryu Jae-Chun
    • Environmental Analysis Health and Toxicology
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    • v.21 no.3 s.54
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    • pp.209-218
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    • 2006
  • 합성화학물질들이 환경으로의 유입은 인체에는 물론 환경생태계에 많은 영향을 미치므로 이들의 유해성 검증은 매우 중요한 일이라 할 수 있다. 실제 산업체에서 사용되는 수많은 화학물질들의 유전적 손상 유발유무는 유해성검증에서 무엇보다 중요한 일이라 할 수 있다. 이에 산업체 공정과정에서 널리 사용되는 것으로 알려진 17종의 합성화학물질에 대해 마우스의 말초 혈의 망상적혈구를 이용한 in vivo 소핵시험을 수행하여, 소핵형성 유발유무를 관찰하였다. 양성대조군으로 사용된 mitomycin C는 음성대조군과 비교시 유의하게 소핵을 유발하는 반면, 비교적 마우스에서 높은 50% 치사량을 보이는 benzoyl chloride, p-toluene sulfonic acid 및 4,4'-sulfonyldianiline 등의 합성물질들을 포함한 총 17종의 물질들은 본 실험결과 통계적으로 유의하게 소핵을 유발하지 않는 것을 관찰 할 수 있었다.

28-day Repeated-dose Toxicity Study of Flutamide, an Anti- androgenic Agent, in Rats: Establishment of Screening Methods for Endocrine Disruptors (내분비계 장애물질 검색법의 확립을 위한 항안드로젠성 물질 flutamide의 랫드 28일 반복투여 독성실험)

  • 정문구;김종춘;임광현;하창수
    • Toxicological Research
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    • v.16 no.2
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    • pp.163-172
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    • 2000
  • Recently, there is a worldwide concern that a great number of man-made chemicals have a hormone-like action both in humans and in animals. DECD is developing screening programs using validated test systems to determine whether certain substances may have an effect in humans. In the present study. the establishment oj repeated-dose toxicity test method was tried. Flutamide. an anti-androgenic agent. was administered by gavage to Sprague-Dawley rats for 28 days at dose levels of 0. 0.5. 3 and 18 mg/kg body weight (10-15 rats/sex/group) to examine the effects on general findings. especially reproductive and endocrine parameters. Clinical signs. body weights, food consumption, and sexual cycle were checked and measured. For the gross and microscopic examinations. 10 rats/sex/group were sacrificed at the end of dosing period and the remaining animals of control and high dose groups (5 each) were sacrificed after 14 days recovery. Examinations for hematology and clinical chemistry were carried out at necropsy. There were no treatment-related changes in clinical signs. body weights, food consumption. gross necropsy. hematology and clinical chemistry at all doses of both sexes. The period and regularity of sexual cycle were not adversely affected at all doses by the test agent. At 18 mg/kg. both decreased weights of prostate, seminal vesicle and epididymis in males and increased weights of spleen and thymus in females were observed. In addition, decreased number of spermatids and sperms. increased serum testosterone concentration and increased incidence (100%) of interstitial cell hyperplasia were seen in males. At 18 mg/kg of the recovery group. decreased prostate weight. reduced sperm count and increased incidence (20%) of interstitial cell hyperplasia in males and increased thymus weight in females were observed. At 3 mg/kg. reduced sperm count was found. There were no adverse effects on parameters examined at 0.5 mg/kg of both sexes. The results suggested that the potential target organs of flutamide may be accessory sexual glands including testes for males and spleen and thymus for females. Taken together. this test method was found to be a useful screening test system for endocrine disrupting chemicals.

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Neuroprotection of Dopaminergic Neurons by Hominis Placenta Herbal Acupuncture in in vitro and in vivo Models of Parkinson's Disease Induced by MPP+/MPTP Toxicity

  • Jun, Hyung Joon;Nam, Sang Soo;Kim, Young Suk
    • Journal of Acupuncture Research
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    • v.32 no.1
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    • pp.23-36
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    • 2015
  • Objectives : This study was designed to investigate the neuroprotective effects of Hominis-Placenta (HP)on dopaminergic neurons. Methods : We examined the effect of invitro administration of HP against 1-methyl-4-phenylpyridinium( MPP+)-induced dopaminergic cell loss in primary mesencephalic culture and also used behavioral tests and performed analysis in the striatum and the substantia nigra of mouse brain, to confirm the effect of HP on dopaminergic neurons in an invivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse model. Animals were assigned to four groups: (1) Group 1(vehicle-treatedgroup), (2) Group 2(MPTPonlytreated group), (3) Group 3(MPTP+ saline-treated/$ST_{36}$ group), and (4) Group 4(MPTP+HP-treated/$ST_{36}$ group). HP at $20{\mu}L$ of 48 mg/kg dose was injected at $ST_{36}$ for 4 weeks at 2-day intervals. MPTP in saline was injected intraperitoneally each day for 5 days from the $8_{th}$ treatment of HP. We performed the pole test and rota-rod test on the first and seventh day after the last MPTP injection. To investigate the effect of HP on dopaminergic neurons, we performed analysis in the striatum and the substantia nigra of mouse brain after treatment with HP and/or MPTP. Results : Treatment with HP had no influence on cell proliferation and caused no cell toxicity in $PC_{12}$ and $HT_{22}$ cells. Our study showed that HP significantly prevented cell loss and protected neurites against MPP+ toxicity. Although the invivo treatment of HP herbal acupuncture at $ST_{36}$ showed a tendency to improve movement ability and protected dopaminergic cells and fibers in the substantia nigra and the striatum, it did not show significant changes compared with the MPTP treated group. Conclusions : These data suggest that HP could be a potential treatment strategy in neurodegenerative diseases such as Parkinson's disease.

Effect of Chungganhaeju-hwan in Ethanol-induced Neuronal Cell Damage (청간해주환(淸肝解酒丸)의 알코올 유도 뇌신경세포 손상에 대한 보호 효과)

  • Ju, Mi-Sun;Kim, Hyo-Geun;Cho, Hae-Jeong;Sim, Jae-Jong;Jeon, Yong-Jun;Oh, Myung-Sook
    • The Korea Journal of Herbology
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    • v.26 no.3
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    • pp.75-82
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    • 2011
  • Objectives : In this study, we evaluated the effect of Chungganhaeju-hwan(CGHJH) on hydrogen peroxide($H_2O_2$)-induced and ethanol(EtOH)-induced neuronal damage in vitro and in vivo, respectively. Methods:We carried out the anti-oxidant effects of CGHJH against hydrogen peroxide($H_2O_2$)-induced toxicity in HT22 and PC12 cells using thiazolyl blue tetrazolium bromide. Then, to investigate the protective effect on CGHJH against EtOH-induced memory impairment and hippocampal cell damage in male ICR mice, we performed novel object recognition test(NORT), and analysed the brain tissues after immunohistochemistry and western blotting. Results:CGHJH showed protective effect from $H_2O_2$-induced cell toxicity at doses of $1\sim100{\mu}g$/mL in both HT22 and PC12 cells. CGHJH had also recovery effect from EtOH-induced memory impairment in ICR mice from NORT and it protected hippocampal cells against EtOH toxicity in the result of cresyl violet and NeuN immunoreactivity. Conclusion : These results demonstrate that CGHJH has protective effect in neuronal cells against $H_2O_2$ and EtOH toxicities and this effect could be a main role of recovery effect on EtOH-induced memory loss.

Hepatoprotective and Blood Alcohol Lowering Effects of Fruit Peduncle Extract of Hovenia dulcis var. Koreana in the In Vitro and in Vivo Animal Models (헛개나무(Hovenia dulcis var. koreana) 과병 열수추출분획물의 간보호 및 혈중 알콜 저하 작용)

  • 나천수;정남철;양규환;김세현;정하숙;동미숙
    • YAKHAK HOEJI
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    • v.48 no.1
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    • pp.34-40
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    • 2004
  • Hovenia dulcis which is distributed in Korea, China and Japan is known to show hepatoprotctive effect and reduce the acute alcohol toxicity. In this study, the hepatoprotective effect against the chemically induced experimental liver injury models and lowering effect of blood alcohol level in animal models acutely administered alcohol by the peduncle extracts of Hovenia dulcis var. koreana were investigated. HdfHW-1, and HdfM-1 which are the extracts of fruit peduncles and young branches with hot water or 70% methanol and followed with 100% methanol, were significantly reduced the $CCl_4$ or D-galactosamine/LPS induced damage in sliced liver. The hot water or methanol extracts of fruit peduncle protected dose-dependently against $CCl_4$ induced toxicity in primary hepatocyte culture and particularly, the amount of LDH release was reduced to the control level at 500 $\mu\textrm{g}$/ml of hot water extracts. HdfHW-1 also decreased the hepatotoxicity induced by $CCl_4$ in rats. The active components of HdfHW-1 seemed to be high molecular weights because 0.2 M NaCl HdfHW-1 fraction was the most effective among NaCl fractions of HdfHW-1 eluted with various concentrations of NaCl on DEAE 650C column chromatography. HdfM and HdfHW were significantly reduced the levels of blood alcohol in rats and mice administered 40% alcohol. These results indicated that the hot water or methanol extracts of fruit peduncle of Hovenia dulcis var. koreana have hepatoprotective effect and may be reduce alcohol toxicity.

Evaluation of Genotoxicity and 14-day Repeat Dose Toxicity of Water Extract of the Mixture of Natural Plants, Anemarrhena and Phellodendron (천연식물자원 지모와 황백피 혼합 수추출물의 안전성평가)

  • Chung, Young-Shin;Park, Cheol-Beom
    • Journal of Food Hygiene and Safety
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    • v.29 no.4
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    • pp.383-390
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    • 2014
  • The safety of a new natural plant composition (ADP) was assessed on the genotoxicity study and 14-day repeat dose toxicity study. ADP contains a mixed water extract obtained from the mixture of Phellodendron cortex (Phellodendron amurense) and Anemarrhena rhizoma (Anemarrhena asphodeloides), and poses the contractile properties mediated by alpha-adrenoceptor of the prostate and urethra as well as antioxidant and anti-inflammatory properties. In order to evaluate genetic safety, in vivo micronucleus test was performed in ICR mice orally administered with three dose levels of 1250, 2500, 5000 mg/kg body weight, and vehicle and positive control. In the 14 days study, Sprague-Dawley rats were treated with ADP at the dose levels of 500, 1000, 2000 mg/kg once a day, and clinical signs, body weights, hematology, serum biochemistry, necropsy findings and organ weights were monitored and examined. In experimental results, ADP treatment, compared with vehicle control, did not induce the micronucleated erythrocytes from mouse bone marrow. In the 14 days study, any significant and toxicological differences in all measurements of parameters were not observed in ADP treatment groups of animals, compared with vehicle treatment. The No-Observed-Adverse-Effect-Level (NOAEL) of ADP in the 14 days study was determined to be greater than 2000 mg/kg/day in both sexes.

Affirmative Effect of Hwaweo-jeon (Huayu-jian) in Osteoblast Cells and Tibia Fracture-induced Mice (화어전(化瘀煎)이 조골세포 및 경골골절 유발 생쥐의 골유합에 미치는 영향)

  • Lee, Soo-Hwan;Parichuk, Kira;Cha, Yun-yeop
    • Journal of Korean Medicine Rehabilitation
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    • v.30 no.1
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    • pp.13-29
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    • 2020
  • Objectives This study was performed to decide the bone union effect of Hwaweo-jeon on tibia fractured mice. Methods In this study, laboratory experiments were implemented by the stage of in vitro and in vivo. In in vitro, MC3T3-E1 cells were treated with various concentration of Hwaweo-jeon extract (HWJ). To investigate effect of HWJ for osteoblast, relative mRNA expression of 5 substances (alkaline phosphatase [ALP], runt-related transcription factor 2 [Runx2], osteocalcin [OCN], osterix [OSX] and collagen type II alpha 1 chain [Col2a1]) was used as a marker of osteogenesis. In order to determine HWJ's effect for fracture healing, relative gene expression level of ALP, Runx2, OCN, OSX and Col2a1 were used to find out the influence to osteoblast. Furthermore, receptor activator of nuclear factor kappa-B ligand and osteoprotegerin relative mRNA expression were used to estimate the impact to osteoclast. Also, X-ray was used for the purpose of identifying bone union in tibia-fracture mouse model. Results In in vitro experiment, most part of relative mRNA expression were increased compared to control group. In in vivo and in vitro experiment, HWJ induced osteoblast activitation by verifying relative mRNA expression of 5 substances. And in vivo experiment, we can also identify that HWJ triggered osteoclast activation during early stage of tibia fracture. Furthermore, X-ray pictures show noticeable recovery of tibia fracture. Conclusions HWJ extract promotes bone union by facilitating the osteoblast. But, HWJ may occur liver & kidney toxicity over specific concentration. Therefore, when HWJ is applied to human body, doctors have to follow up the liver function test & renal function test of patient.

Effect of an extract of Bauhinia variegata leaves on chronic arsenic intoxication in mice (Mus musculus): A preliminary study

  • Biswas, Surjyo Jyoti;Ghosh, Goutam
    • CELLMED
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    • v.4 no.3
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    • pp.20.1-20.7
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    • 2014
  • Ethanolic leaf extract of Bauhinia variegata has been tested for its possible antioxidant potentials against sodium arsenite induced toxicity in mice. Mice were randomized into two groups of five and fifty mice. Group I consisting of 5 mice without any treatment with food and water ad libitum which served as normal control. Group II mice were fed with sodium arsenite in drinking water at 100 ppm concentration for two monthsthen they were segregated into five groups which were treated differently. Group II a mice received only arsenic as sodium arsenite with drinking water, Group II b were fed chronically 1 : 20 alcohol to distilled water (vehicle), Group II c, d, e mice were orally fed 50 mg/kg, 150 mg/kg and 250 mg/kg of B. variegata leaf extract of once daily for 15 and 30 days respectively along with arsenic. Several toxicity marker enzymes such as gamma glutamyl transferase, lactate dehydrogenase, aspartate and alanine aminotransferase, acid and alkaline phosphatase, catalase and superoxide dismutase along with haematological variables such as glucose 6-phosphate dehydrogenase, creatinine, bilirubin, haemoglobin and sugar in different groups of treated and control mice were studied. Results obtained from the in vivo experiment revealed that administration of sodium arsenite caused a significant increase in some enzymes while decrease in some. A similar trend was also observed with haematological variables. In contrast B. variegata treatment at 150 mg/kg favourably modulated these alterations and maintained the antioxidant status than other two doses i.e. 50 mg/kg and 250 mg/kg thereby making it a good candidate to be used as supportive palliating measures in arsenic induced toxicity.

Invirto alternatives to photosensitization Test (광감작성 시험에서의 동물대체 시험법)

  • Lee, Ho;Nam, Ki-Taek;Koh, Jae-Sook;Park, Won-Jae
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.22 no.1
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    • pp.84-101
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    • 1996
  • To minimize the use of animals in toxicity testing, and to reduce the cost in vivo test, more rational test method was described which determines, in the same animal, photoxic and photoallergic potential of a substance, and is daptable to routine testing. The other purpose of this study was to investigate the usefulness of in vivo alternatives ; photostability and spectrophotometric carbonyl assay. In this modified photosensitization model, animal numbers and resting periods, the number and method of topical application were simplified. Two positive photoreactive agents, Benzocaine and 6-methyl coumarine, showed a similar photoallergic potential to that of Ichikawa's method. Two sunscreens, Octyl methoxy cinnamate, Butyl methoxyl dibenzoyl methane, hardly showed photoallergic potentials. The photostability test could be used in the step of prescreening of photosensitization potential because most of the photoreactive agents represented the reduction of more than 20% in the absorbance. And photoreactive agents have a high potential of photosensitization in the sddessment of spectrophotometric carbonyl level although two sunscreens have a low possibility of photosensitization. Therefore this method was assumed as a valuable in vivo alternatives in the respect even in the very low concentrations which phototoxicity test using almonella showed no phototoxic potential.

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Genotoxicological and Acute Toxicological Safeties of Gamma Irradiated Beef (감마선조사 쇠고기의 유전독성 및 급성독성학적 안전성평가)

  • Kang, Il-Jun;Kwak, Hee-Jin;Lee, Byung-Hoon;Kim, Kwang-Hoon;Byun, Myung-Woo;Yook, Hong-Sun
    • Korean Journal of Food Science and Technology
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    • v.30 no.4
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    • pp.775-780
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    • 1998
  • Gamma irradiation at 5 kGy was applied to beefs for evaluation of their possible genotoxicity and acute oral toxicity. The genotoxicity of 5 kGy irradiated beef was evaluated by Salmonella typhimurium reversion assay and in vivo micronucleus assay using mouse bone marrow cells. The results were negative in the bacterial reversion assay with S. typhimurium TA98, TA100, TA1535, TA1537. Clastogenic effects were not shown in vivo mouse micronucleus assay at 5 kGy dose tested. In an acute toxicity test, 5 kGy-irradiated beef was administrated orally at a dose level of 313 to 5,000 mg/kg, and then number of deaths, clinical signs, body weights, and pathological examinations were examined daily for 14 days post-administration. The results indicate that 5 kGy irradiated beef did not show any toxic effect on mice and oral $LD_{50}$ value was over 5,000 mg/kg on ICR mice.

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