• 제목/요약/키워드: acute and subacute toxicity

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님추출물의 경구투여에 따른 랫드의 신장독성 연구 (Study of Kidney Toxicity of Azadirachta Indica Extract for Oral Administration in Rats)

  • 윤현주;최미선;조현조;한범석;박경훈;오진아;조남준;백민경
    • 한국환경농학회지
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    • 제33권2호
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    • pp.103-110
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    • 2014
  • Azadirachta indica는 살충작용을 가진 약용 식물 중 하나로 우리나라에서 유기농업자재로 널리 사용되고 있다. 본 연구에서는 님추출물의 인체 안전성을 확인하기 위하여, SD 랫드를 이용하여 님추출물의 급성경구독성시험과 4주 반복투여 경구독성시험을 수행하여 신장의 조직변화 및 혈액생화학적 지표를 관찰하였다. 급성 독성시험 결과 님추출물의 $LD_{50}$은 2.0 g/Kg이상으로 나타났다. 반복투여 경구독성시험으로 님추출물을 각각 0.5, 1.0, 2.0 g/Kg으로 투여한 결과, 체중변화, 사료 및 물 섭취량에서는 유의적인 차이가 없었으며, 시험물질투여군의 상대 신장중량 또한 유의적인 차이를 보이지 않았다. 혈중 CREA는 수컷에서 님추출물 고용량 투여군에서 유의적으로 증가하였으나 BUN은 투여용량이 증가할수록 유의적으로 감소하였다. 신장과 관련된 혈중 지표인 CHO는 암컷에서 시험물질 투여군의 용량이 증가할수록 유의적으로 증가하였다. 그러나, 조직 병리학적 분석결과 모든 시험물질투여군에서 이상이 관찰되지 않았다. 이상의 결과를 종합하여 볼 때, 님추출물은 암컷에서 혈중 콜레스테롤 증가 경향을 보인 것을 제외하고는 모든 용량처리군에서 신장에 독성 영향을 미치지 않는 것으로 생각된다.

S-Bioallethrin의 독성에 미치는 N-Octyl bicycloheptene dicarboximide의 영향 (Effect of N-Octyl bicycloheptene dicarboximide on the Toxicity of S-Bioallethrin in Rats)

  • 홍사욱;장준식
    • Environmental Analysis Health and Toxicology
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    • 제8권1_2호
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    • pp.37-58
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    • 1993
  • In order to investigate the toxicities of S-bioallethrin (5-biol) and its combination treatment with N-octyl bicycloheptene dicarboximide (MGK-264), the acute and subacute toxicity, and enzyme activity test were performed. $LD_{50}$ levels of S-biol and MGK-264 in rats are 640 mg/kg and 3, 280 mg/kg respectively. However, when rats were treated with the mixture of S-biol and MGK-264 (1 : 5 ratio), the $LD_{50}$ was decreased to 545 mg/kg. In serological analysis, ALT and LDH were increased in animals treated with the mixture. Also glucose level was significantly increased after 5 weeks in animals treated with both S-biol and the mixture. Other biochemical parameters such as cytochrome P-450 and NADPH-cytochrome c reductase in the liver and kidney were shown to be not significantly changed. Levels of total ATPase and $mg^{2+}$ ATPase were significantly decreased in the liver of animals treated with the mixture after 4-5 weeks. In addition, S-biol can alone decrease total ATPase activity. Total ATPase activity was also significantly decreased in the kidney after 5 week treatment with the mixture. Similarily, glucose-6-phosphatase activity was significantly decreased in animals treated with the mixture. When either S-biol or MGK-264 was administered, cholinesterase and carboxyesterase activities were slightly decreased but they were significantly decreased when the mixture was administered.

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한국산 재래식 발효메주의 안전성에 관한 연구 (A Study on the Safety of Korean Domestic Fermented Meju)

  • 서화중;정두례
    • 한국식품영양과학회지
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    • 제20권1호
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    • pp.13-20
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    • 1991
  • For this experiment frist the fermented Soybean Meju was prepared by domestic ordinary method of Korean and concentrated Meju suspensoidal extract was made for toxicological test sample on mice and rat. Even the oral dose of 10g extract per kg of mice had not any acute toxicity. So the median lethal dose(LOD50) is lilely to be much greatr or not to be. In comparison of the average weight gain rate for 4 weeks the control and test groups of 0.308g Ex/rat kg and 9.24g Ex/rat kg daily were the much the same as about 19% but 3.08g Ex/rat kg group waas exceptionally 2.7% higher than control For this period all test groups did not show any abnormality in appearance and anatomic findings. In serum GPT GOT alkaline phosphatase and blood urea nitrogen value there were no difference significantly between control and the test groups of 0.308g/rat kg and 3.08g/rat kg but 9.24g/rat kg group was some what higher than control. Especially in cholesterol alkaline phosphatase and blood urea nitrogen value 9.24g/rat kg group or 28days had 100mg/이 37.5u 32mg/이 respectively which were increased significantly. The pathological findings of all test groups especially 9.24g/kg group did not showed any characterized sign of acute or subacute liver damage or intestine lesion. So it is supposed that there is not any tocixants originated from some molds in fermented Korean domestic Meju which is prepared traditionally in winter.

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Oral Acute and Subacute Toxicity studies of Captopril(SR Tablet 25mg) in SD Rats.

  • Shin, Chun-Chul;Song, Si-Whan;Kang, Boo-Hyun;Kim, Eun-Joo;Chi, Heung-Woo;Lee, Kyou-Heung;Paik, Woo-Hyun
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1996년도 춘계학술대회
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    • pp.248-248
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    • 1996
  • 경구투여급성독성시험 : 암수동물의 모든 투여군에서 시험물질투여에 의한 일반증상, 체중변화 및 육안적 부검소견은 관찰되지 않았으며. 따라서 반수치사량(LD$_{50}$)은 암수동물의 경우 5000mg/kg이상이었다. 경구투여아급성독성시험 : SD랫트의 암수 동물에 있어서 Captopril(SR Tablet 25mg)의 2000mg/kg 용량은 확실중독량에 해당되며, 무영향량(NOEL)은 220mg/kg용량이라고 사료되었다.

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Anti-Helicobacter pylori IgY의 안전성 및 임상적 효과 (The Safety and Clinical Test of Anti-Helicobacter pylori IgY)

  • 정순희;김현주;이수원;류영수;박형석;이남형
    • 한국축산식품학회지
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    • 제25권4호
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    • pp.465-471
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    • 2005
  • 본 연구는 H. pylori를 산란계에 과면역시켜서 얻은 anti-H pylori IgY난황 분말의 안전성과 위염 환자에 있어서 H. pylori에 대한 억제 효과를 알아보기 위하여 실시하였다. Anti-H. pylori IgY난황 분말의 안전성 실험은 급성 독성실험과 아급성 독성실험으로 알아보았다. 급성 독성 실험시 식이섭취나 성장 모두 정상적이었고, 마우스의 체중(kg)당 400mg까지 투여했을 때 이상을 관찰할 수 없었다. 아급성 독성실험에서 외관상의 이상현상은 관찰할 수 없었고, 혈청의 CBC 검사에서 백혈구 수치도 정상적이었다. 그리고 소화기관과 간조직의 병리학적 이상은 관찰되지 않았다. 이 결과로 미루어 anti-H pylori IgY난황분말은 독성이 없음이 확인되었다. 임상실험에서는 WSF 분말 급이군의 UBT 수치는 58.65에서 35.33으로 약 23.31 감소하였으며, anti-H pylori IgY 난황분말 혼합 급이군의 UBT 수치는 47.77에서 28.81로 약 17.95 감소 효과를 보였다. WSF 분말 급이군은 anti-H. pylori IgY 난황분말 혼합 급이군보다 UBT 수치의 감소율이 더 크게 나타났다. 이와 같이 임상실험에서 anti-H, pylori IgY는 H. pylori의 억제 효과가 있음이 확인되었다.

Evaluation of analgesic and antiinflammatory activity of Ophiorrhiza nicobarica, an ethnomedicine from Nicobar Islands, India

  • Chattopadhyay, Debprasad;Das, Sonali;Mandal, Asit Baran;Arunachalam, G;Bhattacharya, SK
    • Advances in Traditional Medicine
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    • 제7권4호
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    • pp.395-408
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    • 2007
  • This study reports the analgesic, anti-inflammatory and membrane-stabilizing property of alcoholic extract of Ophiorrhiza nicobarica (ON), a wild herb, used as an anti-infective ethnomedicine of Nicobarese and Shompen tribes of Great Nicobar Island, India. We for the first time investigated the analgesic and antiinflammatory potential of this herb in acute, subacute and chronic model of inflammation in Swiss albino mice and Wistar albino rats, along with sheep RBC-induced sensitivity and membrane stabilization. The acetic acid induced writhing, tail flick and tail immersion tests are used as a model for evaluating analgesic activity; while the carrageenin-induced paw oedema was used as the model for acute inflammation, dextran-induced oedema as sub-acute and cotton-pellateinduced granuloma as chronic inflammatory model. The probable mode by which ON mediate its effect on inflammatory conditions was studied on sheep RBC-induced sensitivity and membrane stabilization. The in vitro results revealed that the ON extract possesses significant (P < 0.05) dose dependent analgesic and antiinflammatory activity at 200 and 300 mg/kg and its fractions at 50 mg/kg, p.o. respectively, compared to the control groups. However, the extract failed to exhibit membrane-stabilizing property as it unable to reduce the level of haemolysis of RBC exposed to hypotonic solution. The acute toxicity studies of ON extract in rats and mice revealed that the extract was nontoxic even up to 3.0 g/kg body weight of the animals, with a high safety profile. We have isolated ursolic acid, ${\beta}$-sitosterol and harmaline respectively, from the bioactive part of the extract. The results indicated that the O. nicobarica is indeed beneficial in primary health care, and suggest that its anti-inflammatory activity may not be related to membrane-stabilization.

Mancozeb이 마우스 비장세포의 IFN-$\gamma$생성능에 미치는 영향 (Effects of Mancozeb on IFN-$\gamma$Production of Mice Splenocytes)

  • 표명윤;정애희
    • Environmental Analysis Health and Toxicology
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    • 제20권3호
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    • pp.243-248
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    • 2005
  • Mancozeb (MCZ), a polymeric complex of zinr and manganese salts of ethylene bisthiocarbamate, is widely used in agriculture as fungicidel, insecticides, and herbicides. MCZ can be occupationally and environmentally exposed to human and has been reported to have detrimental effects on the reproductive system, but the toxicity of MCZ on immune responses has not been systematically investigated. We investigated the effects of MCZ exposure on the activities of murine splenocytes through evaluation of splenocytes cellularity and INF-$\gamma$ synthesis. Splenocytes were examned ex vivo from mice orally treated with various doEes of MCZ for 1 day (acute exposure, 2,100, 5,000, 10,000 mg/kg) or ior 5 consecutive days per week for 4 weeks (subacute exposure,250, 1,000, 1,500 mg/kg/day) fellowed by culture for 2 days in the presence of Con A or PHA plus IL-2. Splenocytes Iron naive mice were cultured with various concentration of MCZ (50, 500, 1,000 ng/ml) in the presence of Con A or PHA plus IL-2 for 2 days in vitro. IFN-$\gamma$ production was decreased with the in vitro exposure to all concentration of MCZ. The spleen cellularity and IFN -$\gamma$ production by splenocytes from MCZ -acutely and - subacutely exposured mice were decreased in comparision with that oi control group.

분말녹용의 약물활성 연구(I) (Pharmacological Studies on Powdered Whole Part of Unossified Antler)

  • 신국현;이은방;김재현;정명숙;조성익
    • 생약학회지
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    • 제20권3호
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    • pp.180-187
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    • 1989
  • Systematic pharmacological studies on powdered whole part of unossified antler obtained from Cervus nippon Temminck var. mantchuricus have been carried out in mice and rats. Powdered antler, with a single oral administration, showed a very weak acute and subacute toxicity; its MLD being >5g/kg orally in mice. On daily oral treatments of the antler for 14 days, it did not cause any significant differences in body weight gain, various organ weights and serum transaminase activities compared to those of the control rats. Powdered antler, with a single oral administration, showed a remarkable analgesic activity as evaluated by writhing syndrome and tail-pressure test, a weak CNS depressant activity as well as a weak immunopotentiating action as evaluated by carbon clearance test in mice. Powdered antler, with repeated treatments, showed a moderate antifatigue effect against immobilized stress and showed significant increases in both adrenal weight and its ascorbic acid content in rats, suggesting that the mode of antifatigue effect of antler is related to adrenal and its components.

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살충제(殺蟲劑) Monocrotophos가 흰쥐에 대한 독성(毒性) 및 혈액중(血液中) Cholinesterase 활성도(活性度)에 미치는 영향(影響) (Acute Toxicity and the Effect of an Insecticide Monocrotophos on plasma Cholinesterase Acitivity in Albino Rat.)

  • 김광포;최인후;양재설
    • 한국환경농학회지
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    • 제7권1호
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    • pp.58-64
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    • 1988
  • 살충제 Monocrotophos의 독성평가(毒性評價)를 위하여 흰쥐에 $1{\sim}4$주동안 투여후 급성(急性) 및 아급성(亞急性) 독성검정(毒性檢定) 그리고 혈액성상(血液性狀) 및 혈장중(血漿中) Cholinesterase(ChE)를 측정(測定)하여 그 변화(變化)를 구명(究明) 하므로서 농약중독(農藥中毒)에 대(對)한 기초자료(基礎資料)를 얻고자 본(本) 시험(試驗)을 실시(實施)한 결과(結果)는 다음과 같다. 1. Monocrotophos의 급성경구(急性經口) 반수치사(半數致死) 약량(藥量)$LD_{50}$은 흰쥐에서 암, 수 각각(各各) 5.1, 8.7mg/kg이었고 복강내(腹腔內) 투여시(投與時)에는 암컷이 4.9mg/kg 수컷이 6.0mg/kg 이었다. 2. Monocrotophos는 경구(經口)에 6.4mg/kg, 복강내(腹腔內) 4.0mg/kg 투여시(投與時)에 4시간(時間)이 지난후 암, 수 모두의 혈장(血漿) ChE 활성도(活性度)를 최대(最大)로 억제(抑制) 시켰고 투여(投與) 24시간(時間) 이후(以後)부터는 점차 회부(回復) 되었다. 3. Monocrotophos를 흰쥐에 4주간(週間) 경구투여(經口投與) 할 때 3.5mg/kg/day 투여군(投與群)에서는 대조군(對照群)에 비(比)해 암, 수 모두 체중증체량(體重增體量)과 수컷에서 사료섭취량이 현저하게 감소(減少) 되었다. 4. 약제 투여시(投與時)에는 혈장(血漿) ChE 활성도(活性度)를 크게 억제(抑制)시켰으나 투여(投與) 중단(中斷)후에는 2주(週)가 지나면서 거의 회부(回復)되었다. 5. 약제투여(藥劑投與)된 쥐의 적혈구(赤血球), 백혈구(白血球), Ht치(値), Hb량(量)에 대(對)한 혈액상(血液狀) 변화(變化)는 거의 없었다.

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Cytotoxicity, Toxicity, and Anticancer Activity of Zingiber Officinale Roscoe Against Cholangiocarcinoma

  • Plengsuriyakarn, Tullayakorn;Viyanant, Vithoon;Eursitthichai, Veerachai;Tesana, Smarn;Chaijaroenkul, Wanna;Itharat, Arunporn;Na-Bangchang, Kesara
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권9호
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    • pp.4597-4606
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    • 2012
  • Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma which arises from the epithelial cells of the bile ducts. The aim of the study was to investigate the cytotoxicity, toxicity, and anticancer activity of a crude ethanolic extract of ginger (Zingiber officinale Roscoe) against CCA. Cytotoxic activity against a CCA cell line (CL-6) was assessed by calcein-AM and Hoechst 33342 assays and anti-oxidant activity was evaluated using the DPPH assay. Investigation of apoptotic activity was performed by DNA fragmentation assay and induction of genes that may be involved in the resistance of CCA to anticancer drugs (MDR1, MRP1, MRP2, and MRP3) was examined by real-time PCR. To investigate anti-CCA activity in vivo, a total of 80 OV and nitrosamine (OV/DMN)-induced CCA hamsters were fed with the ginger extract at doses of 1000, 3000, and 5000 mg/kg body weight daily or every alternate day for 30 days. Control groups consisting of 10 hamsters for each group were fed with 5-fluorouracil (positive control) or distilled water (untreated control). Median $IC_{50}$ (concentration that inhibits cell growth by 50%) values for cytotoxicity and anti-oxidant activities of the crude ethanolic extract of ginger were 10.95, 53.15, and $27.86{\mu}g/ml$, respectively. More than ten DNA fragments were visualized and up to 7-9 fold up-regulation of MDR1 and MRP3 genes was observed following exposure to the ethanolic extract of ginger. Acute and subacute toxicity tests indicated absence of any significant toxicity at the maximum dose of 5,000 mg/kg body weight given by intragastric gavage. The survival time and survival rate of the CCA-bearing hamsters were significantly prolonged compared to the control group (median of 54 vs 17 weeks). Results from these in vitro and in vivo studies thus indicate promising anticancer activity of the crude ethanolic extract of ginger against CCA with the absence of any significant toxicity. Moreover, MDR1 and MRP3 may be involved in conferring resistance of CCA to the ginger extract.