• Title/Summary/Keyword: Toxicity of NO

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Single Oral Dose Toxicity Study of Black Raspberry Extract in Sprague-Dawley Rats (복분자 추출물의 Sprague-Dawley rat를 이용한 단회 경구 투여 독성시험)

  • Lee, Joo Young;Ji, Kon-Young;Song, Kwang Hoon
    • The Korea Journal of Herbology
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    • v.35 no.4
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    • pp.45-50
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    • 2020
  • Objective : This study was performed to evaluate the toxicity after a single oral administration of black raspberry extract to male and female Sprague-Dawley (SD) rats and to determine the approximate lethal dose (ALD). Methods : We previously showed that the black raspberry extract repressed the simvastatin-mediated expression of Proprotein convertase subtilisin/kexin type 9 (PCSK9) and improved Low-Density Lipoprotein cholesterol (LDL-C) uptake by hepatocytes through the induction of the Low-Density Lipoprotein Receptor expression in hepatocytes. The groups consisted of black raspberry extract groups, as an oral dose of 2,000 mg/kg and a control group. 5 weeks SD rats were randomly assigned to 4 groups of 5 rats. Each male and female SD rats were administered orally once. For 14 days after the administration, mortality, clinical signs, changes in body weight, and necropsy findings were observed according to the "Standard for Toxicity Study of Pharmaceuticals" of Korea Food and Drug Administration (KFDA) guideline and "Acute Oral Toxicity- Fixed Dose Procedure" of OECD Test Guideline. Results : There were no cases of mortality in the group administered with 2,000 mg/kg of male and female, and no abnormalities in body weight change and clinical signs. Also, no gross abnormalities were observed at the autopsy. Conclusions : As a result of a single oral administration of the black raspberry extract to SD rats, the ALD was determined to exceed 2,000 mg/kg for both male and female SD rats.

오염된 토양의 중금속 분포와 독성상관 관계 연구

  • 공인철
    • Proceedings of the Korean Society of Soil and Groundwater Environment Conference
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    • 2001.04a
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    • pp.11-14
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    • 2001
  • In this study, the relationship between metals (Cu, Cr, Cd, Zn. Pb, and Fe) 5 fractions and toxicity of soil samples from various contaminated sites in Korea were investigated. Metal toxicity of soils was tested using MetPLATE$^{TM}$ test kit, which is known as metal sensitive and organic insensitive. Significant amount of Fe was found in soils, and metal contents were in the order of Fe>Zn>Pb>Cu>Cr>Cd. Metal levels in organic fraction were rather high for all metals except Fe, and quite high percentages (35~79%) for residual fraction were observed for all metals. There were no significant relationships between the content of each metal fraction and toxicity which showed regression $R^2$in the range of 0.0003~0.414. However, correlation between toxicity and total metal contents showed regression coefficient $R^2$= 0.72. These results showed that the risk evaluation of metals in contaminated sites should be difficult to assess only by the contents of metal distribution because of the complexity of mixture of various metals.s.

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TOXICOLOGICAL STUDIES ON RAW AND PROCESSED (PREBREWED) ACONITI TUBERS; ACUTE, SUBACUTE TOXICITY STUDIES AND ASSAY OF ACONITINE ALKALOIDS (生附子와 修治附子에 관한 毒性연구 : 급성 및 아급성 독성과 Aconitine 알칼로이드 함량분석)

  • Park, Han-Soo;Kim, Seung-Hee;Kim, Pu-Young;Chang, Il-Moo
    • Toxicological Research
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    • v.6 no.1
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    • pp.41-49
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    • 1990
  • Aconiti Tuber is the root of Aconitum sp (Ranunclaceae) which has been considered as one of the most important medicinal plant having cordiotonic, diuretic and analgesic effect. On the other hand, it has been known that Aconiti Tuber contained toxic agent, aconitine alkaloids so that only processed Aconiti Tubers have been used as herbal drug traditionally. For the safety evaluation of processed Aconiti Tuber, quantitative determination of aconitine and acute, subacute toxicity test were performed on 5 commercial processed Aconiti Tubers. Arapid and precise method using HPLC has been developed for the separation and determination of aconitine. Samples were extracted with hydrochloric acid (pH3) and hot water decoction. In case of d-HCL extracts, the contents of aconitine were from 0.08 mg/g to trace. But in case of hot water decoction extracts, the contents of aconitine were not detected. For the investigation of Aconiti Tuber toxicity in rats, hot water decoction samples and methanol extracts were tested. 1) Acute toxicity test Hot water decoction sample and methanol extracts from Aconiti Tuber did not show any toxic effects in rats by an oral administration. $LD_50values of 2 extracts were above 10.0 g/kg. 2) Subacute toxicity study In the repeated administration study, hot water decoction samples were given orally to Sprague-Dawlay rats for 2 week at daily doses of 5.0 g/kg. The results are as follows; No toxic manifestation, body weight changes and lethality were observed during wxperimental period. There were no significant changes in serum enzyme activities such as GOT, GPT, LDH, ALP between treated and control groups. However CPK values were decreased in the Subuja-treated group. (P<0.01). In addition, no gross and microscopic changes were noted in Aconiti Tuber-treated groups.

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Endocrine Disruptors in Developing Embryo on Daphnia magna

  • Kim, Pan-Gyi;Hwang, Seong-Hee
    • Journal of Environmental Health Sciences
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    • v.28 no.4
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    • pp.17-22
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    • 2002
  • In crustaceans, as in other arthropods, the molt cycle and the physiological process of growth are controlled by molting hormones (MH) which are steroid hormones, the ecdysteroids. Ecdysteroids are major arthropod hormones which control both development (embryonic and larval molts, metamorphosis) and reproduction. The purpose of the present study was to evaluate both fenarimol and methoprene for embryotoxicity to daphnids. The embryotoxicity associated with each compound was assessed to discern whether the embryotoxicity of methoprene might be due to ecdysone agonist and the ecdysone antagonistic effects of fenarimol on Daphnia embryo. Exposure of daphnids for three weeks to 50 M methoprene resulted in a significantly high incidence of offspring that exhibited general toxicity. This exposure concentration had significant effects on the overall number of embryo death. However, exposure to 3 or 1 $\mu$M fenarimol were no significant effects on the embryo toxicity. The incidence of both of these toxicity increased with methoprene exposure. This observation suggest that methoprene showed embryonic general toxicity during embryo development, while, only fenarimol showed weak general toxicity with early stages of embryonic development.

Developmental toxicity and anti-inflammatory effect of the soft coral Dendronephthya gigantea collected from Jeju Island in zebrafish model

  • Lee, Seung-Hong
    • Fisheries and Aquatic Sciences
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    • v.20 no.12
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    • pp.32.1-32.7
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    • 2017
  • Recent in vitro studies have demonstrated that extract of soft coral Dendronephthya gigantea (SCDE) had strong anti-inflammatory activities. However, the direct effects of SCDE on anti-inflammatory activities in vivo model remained to be determined. Therefore, the present study was designed to assess in vivo anti-inflammatory effect of SCDE using lipopolysaccharide (LPS)-stimulated zebrafish model. We also investigated whether SCDE has toxic effects in zebrafish model. The survival, heart beat rate, and developmental abnormalities were no significant change in the zebrafish embryos exposed to at a concentration below $100{\mu}g/ml$ of SCDE. However, lethal toxicity was caused after exposure to 200 and $400{\mu}g/ml$ of SCDE. Treating zebrafish model with LPS treatment significantly increased the reactive oxygen species (ROS) and nitric oxide (NO) generation. However, SCDE inhibited this LPS-stimulated ROS and NO generation in a dose-dependent manner. These results show that SCDE alleviated inflammation by inhibiting the ROS and NO generation induced by LPS treatment. In addition, SCDE has a protective effect against the cell damage induced by LPS exposure in zebrafish embryos. This outcome could explain the profound anti-inflammatory effect of SCDE both in vitro as well as in vivo, suggesting that the SCDE might be a strong anti-inflammatory agent.

14 Days Repeat Oral Dose Toxicity of Low Molecular Weight Fucoidan in Rats

  • Yoon, Hyun-Soo;Shin, Yong-Kyu;Lee, Seon-Ha;Lee, Dong-Sub;Jung, Young-Mi;Lee, Hyeung-Sik;Ku, Sae-Kwang
    • Biomolecules & Therapeutics
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    • v.18 no.1
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    • pp.111-121
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    • 2010
  • In order to investigate the preliminary repeat oral dose toxicity and to determine the highest dosage for further 4-week repeated dose toxicity test, Low Molecular Weight Fucoidan (LMF) has been showed various pharmacological effects, was orally administered to female and male rats, once a day for 14 days at dose levels of 2,000, 1,000, 500 and 0 (vehicle control) mg/kg (body weights) in a volume of 10 ml/kg. The mortality and changes on the body weights, clinical signs, hematology, serum biochemistry and gross observations were monitored with organ weight and histopathology of principle organs. As the results of 14-day repeated oral treatment of LMF, no LMF treatment related mortalities were detected up to 2,000 mg/kg in both male and female rats, respectively. In addition, no noticeable changes on the body weight and clinical signs were detected except for significant decreases on the body weights and gains restricted to male 2,000 mg/kg treated groups as compared with male vehicle control. No meaningful changes on the organ weights, hematological, serum biochemistrical, gross and histopathological findings were observed. Therefore the highest dosage in the 4-week repeated dose toxicity test is suggested as 2,000 mg/kg in both female and male rats, respectively.

Acute and Subacute Toxicity Studies of l-Muscone in Rats (랫드에서 l-muscone의 급성독성 및 아급성독성시험 연구)

  • 오승민;연제덕;남혜윤;박대규;조명행;정규혁
    • Toxicological Research
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    • v.13 no.4
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    • pp.435-447
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    • 1997
  • l-Muscone is synthesized for use as substitutive material of musk which is the active ingredient of woohwangchungsimwon. The objective of this investigation was to evaluate the acute and subacute toxicity of l-muscone in rats. In oral acute toxicity test, SPF Sprague-Dawley male and female rats were gayaged with l-muscone of two doses(0, 5.0 g/kg). No dead animal and abnormal autopsy findings were found in control and treated group. Body weights were slightly decreased in both sexes of rats treated with 5.0 g/kg. Therefore, oral $LD_{50}$ of l-muscone was consider to be higher than 5.0 g/kg in male and female rats. In intraperitoneal acute toxicity test, rats were injected intraperitoneally with dosages of 0, 1,000, 1,316, 1,732, 2,279 and 3.000 mg/kg. Decreased body weights and motor activities were observed at high dose group. Intraperitoneal $LD_{50}$ of l-muscone were 1,920 mg/kg in male and female rats. In the subacute study, l-muscone was administrated orally to both sexes of rats for 4 weeks as several doses(0, 10, 100 and 1,000 mg/kg). There were neither dead animals nor significant changes of body weights during the experimental period. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, hematology, serum biochemical analysist and other findings. Above data suggest that no observed adverse effect level of l-muscone in rats might be over 1,000 mg/kg/day in this study.

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Single Dose Toxicity Study of Hwangiaegongjinbo, an Invigorator, in Mice and Rats (마우스 및 랫드에서 자양강장제 황제공진보의 단회투여독성시험)

  • 이정남;박창신;김홍표;황성연;정운계
    • Toxicological Research
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    • v.18 no.1
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    • pp.73-77
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    • 2002
  • The single dose toxicity of Hwangiaegongjinbo, an invigorator developed by Korea Medical Science Institute was evaluated in ICR mice and Sprague-Dawley rats. The aqueous solution of freeze-dried powder of Hwangiaegongjinbo or its original solution was once administrated orally to both sexes of mice and rats at dose of 2000 mg/kg, the recommended upper limit dose for acute toxicity. Water was administered to another group as control. after single adminstration, sign of toxicity were observed every hour for the first 6 hours and every day for 14 days. Neither sign그cant toxic sign nor death was observed during the observation period. In addition, no pathological changes were noticed in macroscopic examination at necropsy in those treated group. These results indicated that $LD_{50}$ of Hwangiaegongjinbo is greater than 2000 mg/kg in ICR mice and Sprague-Dawley rats.

Single and Four-Week Oral Toxicity Studies of Difructose Dianhydrides (DFA IV) in Sprague-Dawley Rats (Difructose Dianhydrides (DFA IV)의 랫드를 이용한 단회 및 4주간 반복 경구투여 독성시험)

  • Lee Chang-Woo;Lee Myong-Lyoll;Kim Hwan-Mook;Yoon Won-Kee;Kim Seung-Hwan;Son Hwa-Young;Kim Hyoung-Chin
    • Toxicological Research
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    • v.20 no.3
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    • pp.263-272
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    • 2004
  • This study was to investigate single and repeated-dose toxicities of DFA IV, a new candidate of nutraceutical which has preventive effect on anemia and osteoporosis. In single-dose oral toxicity study, the test article were administered once by gavage to rats at dose level of 0, 2,000 and 5,000 mg/kg. No dead animal, abnormal sign and abnormal necropsy finding was found in control and treated groups. Thus the approximate lethal dose of DFA IV was considered to be higher than 5,000 mg/kg in rats. In four week repeated dose oral toxicity study, the test article was administered once daily by gavage to rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg. No abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, hematological findings, necropsy findings, organ weights and histopathological findings. In urinalysis, specific gravity was increased in 2,000 mg/kg groups of male rats. In serum biochemical analysis, creatine phosphokinase was increased in all treatment groups of male rats. These increases in urine specific gravity and serum creatine phosphokinase activity were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, four week repeated oral dose of DFA IV to rats did not cause apparent toxicological change at the dose of 500, 1,000 or 2000 mg/kg body weight. Thus it is suggested that no-observed-adverse-effect level (NOAEL) of DFA IV in rats would be 2,000 mg/kg/day body weight.

Acute Toxicity Study on Gumiganghwal-tang and Fermented Gumiganghwal-tang Extracts (구미강활탕 및 발효 구미강활탕 추출물의 급성독성 연구)

  • Park, Hwayong;Hwang, Youn-Hwan;Jang, Doorye;Ha, Jeong-Ho;Jung, Kiyoun;Ma, Jin Yeul
    • Herbal Formula Science
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    • v.20 no.2
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    • pp.93-102
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    • 2012
  • Objectives : Traditional medicine Gumiganghwal-tang (GT) has been used in Asia to treat inflammatory diseases including common cold, pain, fever, and algor. In this study we investigated the acute toxicity and safety of GT and fermented GT (FGT). Methods : Acute toxicity and safety were evaluated in male and female ICR mice orally administered 0 (control) and 2,000 mg/kg of GT and FGT. After the administration of GT and FGT, we observed mortality, body weight, clinical symptoms. After necropsy, organ weights were measured and blood analysis was performed. Results : There was no mortality and clinical symptoms according to the administration of GT and FGT. Comparing with control group, there were no significant alterations on the organ weight, complete blood cell count and biochemical parameters. Conclusions : Median lethal dose of GT and FGT considered to be over 2,000 mg/kg in both male and female mice, and recognized as safe with no toxicity.