• 제목/요약/키워드: chronic toxicity

검색결과 305건 처리시간 0.023초

인진청간탕가미방(茵蔯淸肝湯加味方)이 간세포(肝細胞)의 증식능력(增殖能力)에 미치는 영향(影響) (The Effect of Injinchunggantang-derivative on Proliferation of Hepatocyte)

  • 박용진;김영철;이장훈;우홍정
    • 대한한의학회지
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    • 제19권1호
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    • pp.145-164
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    • 1998
  • The purpose of this study is to evaluate the effect of Injinchunggantang-derivative on proliferation of hepatocyte in rats. Cell viability is studied by MTI assay. The gene related to cell replication such as p53, waf1, bcl-2 and $bcl-_{X_L}$ is quantitized by quantitative RT-PCR and the proteins coded by these genes are studied by Western blotting. The results are as follows. 1. The hepatocytes cultured in medium with lnjinchunggantang-derivative showed better viability compared with control grroup in MTI assay, and the hepatocytes cultured in medium with the Injinchunggantang-derivative-and-ethanol-mixed group showed better viability than the hepatocytes cultrued in 10% ethanol culture medium(control group), noting that Injinchunggantang-derivative has protective effect on hepatocyte injury. There was no dose- and time-dependence. 2. In quantitative RT-PCR, i) Bel-2 gene increased significantly both in Injinchunggantang-derivative group and in Injinchunggantang-derivative-and-ethanol-mixed group, while it showed no significant increase or decrease in other group. ii) $Bcl-_{X_L}$ gene increased significantly in Injinchunggantang-derivative group as well as in Injinchunggantang-deri vative-and-ethanol -mixed group. iii) P53 gene showed no significant increase or decrease in hepatocytes cultured in medium with 10% ethanol and in hepatocytes cultured in medium with Injinchunggantang-derivative-and-ethanol-mixed group, suggesting that 10% ethanol induced cell toxicity, thus increased p53 gene expression. iv) Wafl gene showed no significant increase or decrease in hepatocytes cutured in medium with Injinchtrnggantang-derivative, while increased in hepatocytes cultured in medium with 10% ethanol and in hepatocytes cultured in medium with Injinchtrnggantang-derivative-andethanol-mixed group, suggesting that 10% ethanol induced cell toxicity increased wafl gene expression. 3. In the study on protein by western blotting, the band of bcl-2 and $bcl-_{X_L}$ were widened in Injinchtrnggantang-derivative group. Especially the amount of $bcl-_{X_L}$ increased significantly compared with other groups. But in the study on p53 and wafl, there was no significant difference among those groups. Above study shows that Injinchunggantang-derivative has good effect on cell viability and that the genes resistant to cell death such as bcl-2 and $bcl-_{X_L}$ are induced by Injinchunggantang-derivative to resist to cell death by toxic agent And this is reconfirmed in protein study using' western blotting: These results suggest that Injinchunggantang-derivative has inhibitory effect on cell death as well as protective effect on hepatocyte. Therefore this prescription is recommended in various liver diseases such as chronic liver disease and-induced hepatic injury.

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넙치, Paralichthys olivaceus 자어의 생존과 성장에 미치는 암모니아의 영향 (Effects of Ammina on Survival and Growth of the Flounder Larva, Paralichthys olivaceus)

  • 김형수;김흥윤;진평
    • 한국수산과학회지
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    • 제30권3호
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    • pp.488-495
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    • 1997
  • 넙치, Paralichthys olivaceus의 자어의 생존과 성장에 미치는 암모니아의 급성 및 만성독성 영향을 단기 독성시험법에 준하여 생물검정시험을 실시하고 자어의 성장단계별 암모니아 내성 및 성장에 미치는 영향농도를 산출하였다. $96hr-LC_{50}$ 부화후 7일이 경과한 자어가 $0.300mg\;NH_3/\ell$, 21일된 것은 $0.572mg\;NH_3/\ell$로 증가하다가 부화후 23일째에는 $1023mg\;NH_3/\ell로 증가하여 넘치 자어는 성장단계의 초기에 암모니아의 독성에 민감하고 성장하면서 강한 내성을 보이는 것으로 나타났다. 부화후 경과일수와 비이온성 암모니아의 농도(X)에 대한 $96hr-LC_{50}(Y)$과의 관계식은 $Y=0.0516+0.034{\cdot}X(r=0.854)$였다. 부화 후 1, 3, 5일째의 자어에서 $24hr-LC_{50}$은 부화후 경과일수가 길어질수록 높았으나, 노출시간이 지속되이도 $LC_{50}$은 매우 완만하게 감소하여 threshold $LC_{50}$ 각각 $0.293mg\;NH_3/\ell,\;0.248mg\;NH_3/\ell$ 이었다. 부화 후 16일째의 자어를 암모니아 농도별로 7일간 노출시킨 후의 생존율은 대조구의 경우 $96.7\%,\;0.341mg\;NH_3/\ell$에서는 $83.3\%$였으며, 자어의 체장과 체중은 암모니아 농도가 높을수록 유의하게 감소하였다. 체장에 대한 NOEC와 LOEC는 각각 0.102 및 0.151mg $NH_3/\ell$, 체중에 있어서는 각각 0.151 및 $0.198mg\;NH_3/\ell$으로 체장성장에 미치는 영향이 큰 것으로 추정되었다. 자어의 체장측정치에 대한 변동계수 (CV, coefficient of variation)는 암모니아 농도가 증가할수록 높아져서 고농도일수록 체장성장은 느리고 개체간 체장변이가 많았다.

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한국산 고사리의 독성조사에 관한 연구 (A Toxicological Study of Young Fronds of Bracken Fern (Pteridium aquilinum var latiusculum) Collected in Kwang Ju Area)

  • 서화중;이명렬
    • 한국식품영양과학회지
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    • 제18권3호
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    • pp.255-264
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    • 1989
  • 고사리의 ethanol extract를 독성실험한 결과는 mouse에 시료 10g/kg까지는 급성독$(LD_{50})$을 나타내지 않았다. Rat에 매일 시료40mg/kg, 400mg/kg, 1200mg/kg을 경구투여한 처음 7일간에는 체중, 해부소견, 혈액의 생화학적 검사에서 별이상이 없었다. 14일째 전시료투여군의 체중증가율은 대조군보다 평균 약 7% 감소를 보이고 혈청의 생화학적 측정치가 대부분 약간 증가하였다. 21일째 400mg/kg군과 1200mg/kg군의 체중증가율이 대조군보다 $6.7{\sim}5.7%$ 감소되고 1200mg/kg군 1필이 황색간증세를 보였다. 모든 시험군 GPT 및 GOT는 각각 $88{\sim}102u$$164{\sim}200u$로 증가하고 alkaline phosphatase도 상승하여 중독의 징후를 보였다. 28일째 400mg/kg군과 1200mg/kg군의 체중증가율이 대조군보다 감소되고 이들군에서 각각 $1{\sim}2$필이 황색간을 보였다. 1200mg/kg군 2필이 소장염을 보였다. 모든 시험군은 GPT $92{\sim}116u$와 GOT $56{\sim}215u$ 및 alkaline phosphatase $57{\sim}70u$로 증가 되었다.

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랫드에서 향부자 추출물의 13주 반복 경구투여 독성평가 (Toxicity Assessment of Cyperi rhizoma Aqueous Extract Orally Administered to Rats for 13 Consecutive Weeks)

  • 한소리;한형윤;박희진;민병선;정문구;문경식;정자영;노항식;석지현;김상겸
    • 약학회지
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    • 제57권4호
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    • pp.258-264
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    • 2013
  • Herbal medicine has been traditionally used in Asian countries for a long time. Many pharmacological effects are identified in the herbs and these herbs are believed to be safe for human. However, the safety or adverse effect of some traditional herbal medicines has not been established. We have chosen Cyperi rhizoma based on the Korea Herbal Pharmacopoeia and which have been widely used for an anti-inflammatory effect in Korea. The object of the study was to evaluate safety of Cyperi rhizoma in rats. The aqueous extract of Cyperi rhizoma was prepared according to the standard hot water extraction method of the Korea Pharmacopoeia. In the sub-chronic study, the aqueous extract of Cyperi rhizoma was orally administered once daily as 0, 125, 250, 500, 1000 and 2000 mg/kg/day to male and female F344 rats for 13 weeks. There were no treatment related abnormalities in mortality, clinical signs, food consumption, ophthalmologic examination, hematology, serum chemistry, urinalysis, gross observation, organ weight and histopathologic examination. In conclusion, The NOAEL (No Observed Adverse Effect Level) for Cyperi rhizoma aqueous extract was determined as more than 2000 mg/kg/day in the present experimental condition.

유산균을 이용한 대두 발효 추출물이 면역계 활성에 미치는 영향 (Effects of soybean extracts fermented with Lactic acid bacteria on immune system activity)

  • 박병두;김혜자
    • 대한예방한의학회지
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    • 제16권3호
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    • pp.139-153
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    • 2012
  • Objectives : NK cells are spontaneously cytotoxic lymphocytes. These are not only important parts in the first line of defence against bacterial and viral infections of outside, but they may also play a critical role in chronic viral diseases. NK cells kill their targets spontaneously, without the need for prior sensitization and class I MHC restriction by the regulation of cytolytic functions and secretion of a variety of cytokines, such as interleukin-12(IL-12), MCP-1, IL-6, TNF-${\alpha}$, IFN-${\gamma}$. In addition, macrophage and NK cells cooperate through the production of cell mediates. These cooperation and modulation are one of major factors to prevent for evading immune surveillance of cancer. Hence, it could be assumed that if any candidate to enhance activities of macrophage and NK cell, it is considered as a potentially useful agents against cancer. Methods : In our study, to investigate effect of fermented soybean extracts by Lactic acid bacteria (SFE, soybean fermented extracts) work on intestinal immune cell to maintain general immune modulating and anti-cancer activity. We analyzed NK cytotoxicity assay and gene expressions of cytokine related with macrophage and NK cell activity. Results : In vitro experiment, SFE was verified as safety material for cell toxicicty to tumor cell strain without any toxicity of tumor growth inhibition and various cell strain. Effects of macrophage activity stimulating directly by SFE measured induced cytokine. The studies showed that IL-12 production by stimulation of SFE depended on concentration from 0.16mg/mL to 0.63mg/mL with non toxicity to cell, and it was the best activity at 0.63mg/mL. Besides, the effective concentration of SFE producing TNF-${\alpha}$ is similar to IL-12, but it was the best activity at 1.25mg/mL. The level of MCP-1, IL-6 and IFN-${\gamma}$ depended on concentration from 0.16mg/mL to 10mg/mL, IFN-${\gamma}$ showed the best activity at the effective concentration of 0.63mg/mL. With the result of NK cell activity measurement, the spleen cell of mouse injected SFE had 1.5 times higher killing effect than non injected cell. Conclusions : The result of this studies is that Soybean fermetated extracts(SFE) has possibility to immune aided material for the function not only inhibition of microbial infection to macrophage but also activity of adaption immune and cellular immune system.

INS-1 췌장 베타 세포에서 ferulic acid의 당독성 개선 효과 (Ferulic Acid Protects INS-1 Pancreatic β Cells Against High Glucose-Induced Apoptosi)

  • 박재은;한지숙
    • 생명과학회지
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    • 제34권1호
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    • pp.9-17
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    • 2024
  • 제 2형 당뇨병에서 나타나는 인슐린 분비 감소는 베타세포의 자가사멸에 의한 베타세포질량의 급격한 감소로 인한 것으로 보고되고 있으며, 베타세포의 자가사멸을 촉진하는 요인으로 고혈당에 의한 당독성 및 활성산소종들의 증강에 의한 산화스트레스 등이다. Ferulic acid는 항산화, 항염, 항암 등 다양한 생리활성을 나타내며, 본 연구에서는 고혈당으로 유도된 세포 당독성 개선 효과와 그 기전을 INS-1 췌장 베타세포에서 규명하고자 하였다. Ferulic acid는 고농도 포도당 처리된 INS-1 췌장 베타 세포에서 세포 생존율을 증가시키고, 지질과산화물, 세포 내 ROS 및 NO 수준을 감소시켰다. 세포사멸 관련 인자의 유전자 발현결과 pro-세포자가사멸 인자인 bax, cytochrome c, caspase-3 및 caspase-9의 단백질 발현을 유의적으로 감소시켰고, anti-세포자가사멸 인자인 bcl-2 발현을 증가시켰다. Ferulic acid는 annexin V/I propidium iodide 분석을 통하여 고농도 포도당으로 유도된 세포 사멸을 감소시키고, INS-1 췌장 베타세포에서의 인슐린 분비능을 증가시키는 것으로 사료된다. 따라서ferulic acid는 고농도 포도당으로 손상된 INS-1 췌장 베타세포의 보호효과를 나타낸다.

Effects of total body irradiation-based conditioning on allogeneic stem cell transplantation for pediatric acute leukemia: a single-institution study

  • Park, Jongmoo;Choi, Eun Kyung;Kim, Jong Hoon;Lee, Sang-Wook;Song, Si Yeol;Yoon, Sang Min;Kim, Young Seok;Kim, Su Ssan;Park, Jin-Hong;Park, Jaehyeon;Ahn, Seung Do
    • Radiation Oncology Journal
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    • 제32권3호
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    • pp.198-207
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    • 2014
  • Purpose: To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients. Materials and Methods: From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes. Results: The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%). Conclusion: The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT.

pH 저하가 소백옆새우(Gammarus sobaegensis Ueno)에 미치는 급, 만성 생태독성학적 특성 -1. 정체성 조건- (Ecotoxicological Characteristics of Gammarus sobaegensis Ueno by Acute and Chronic pH Depression on Artificial Static Waters)

  • 박정호;조동현;정근
    • 환경생물
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    • 제18권4호
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    • pp.377-385
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    • 2000
  • 인위적인 산성스트레스가 담수산 소백옆새우(Gammarus sobaegensis Ueno)에 미치는 영향을 정체성 수조건 하에서 급, 만성 생태독성실험을 통해 알아보았다. 급성독성 실험 시 pH 3 대역에서의 반수치사시간($LT_{50}$)은 평균 0.271($\pm$0.146)day로 개체의 크기 또는 먹이의 유무 그리고 주변 환경에 대한 적응능력에 관계없이 일정한 모습을 나타내고 있었다. pH4.0대역에서의 $LT_{50}$은 0.812($\pm$0.377) day로 연장되는 것이 확인되었다. 만성 독성실험의 경우 본 종의 반수치사시간은 pH 3.0일 때 약 6-7 day로 평균 6.313 ($\pm$0.828) day 인 것으로 나타났으며, pH 5.0일 때는 평균 9.475($\pm$4.881)day의 오랜 적응 기간을 갖는 것으로 확인되었다. 이러한 차이는 먹이의 공급유무에 따라 변동이 있다는 것을 알 수 있었고, 또한 주변 환경에 적응이 잘 된 개체일수록 오랜 기간동안 생존한다는 것을 알 수 있었다. 그리고 급, 만성 pH스트레스가 가해진 소백옆새우(G. sobaegensis)의 제 2아가미 표면조직에서 심한 주름현상을 확인할 수 있어, 결국 산성스트레스는 소백옆새우(G. sobaegensis)에 있어서 급성뿐만 아니라 만성적인 영향에서도 최종적으로는 매우 치명적으로 작용한다는 사실을 알 수 있었다.

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홍삼의 장기 투여가 흰쥐 간 대사효소 유도에 미치는 영향 (Modulation of Cytochrome P-450 Induction by Long-Term Supplementation with Korean Red Ginseng to Rats)

  • 임흥빈
    • 한국약용작물학회지
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    • 제15권6호
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    • pp.437-443
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    • 2007
  • 홍삼의 물추출물을 장기간 흰쥐에 급여했을 때 흰쥐 간의 이물질대사효소 활성도 유도에 미치는 영향을 조사하였다. 홍삼 물추출물의 급여농도는 25 mg/kg body weight이었으며, 간의 이물질대사효소 유도제는 항경련제 PB (80 mg/kg)와 발암제 3-MC (20 mg/kg)을 사용하였다. 간에서 이물질대사에 관여하는 cytochrome P-450의 함량, cytochrome P-450 dependent monooxygenase인 ECOD와 BPDM, cytochrome P-450 reductase와 GST의 활성도는 PB와 3-MC 투여에 의해서 대조군과 홍삼투여군 모두 크게 증가되었다. 흰쥐의 나이가 3개월에서는 두 유도제를 투여했을 때 이물질대사효소의 활성은 대조군이 인삼투여군에 비해 상대적으로 더 많이 유도되었다. 그러나 12개월에서는 두 시험군 모두 유도정도가 감소하였으나 홍삼투여군은 그 활성도 감소정도가 대조군에 비해 상대적으로 크지 않았다. 한편 두 그룹 모두 이물질대사 효소 중 cytochrome $B_5$ 함량과 cytochrome $b_5$ reductase의 활성도는 PB와 3-MC 투여에 의해서 뚜렷한 차이를 보이지 않았다. 따라서 이러한 결과는 흰쥐에 홍삼의 장기간 급여는 간에서 효소유도제의 이물질대사효소유도 정도를 조절하여 무독화에 기여할 수 있다는 것을 의미한다.

단삼(丹蔘)이 간성상세포의 섬유화 억제에 미치는 영향 (Inhibitory Effect of Salvia Miltiorrhiza on Fibrogenesis in Rat Hepatic Stellate Cells)

  • 최은경;이장훈;김영철;우홍정
    • 대한한방내과학회지
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    • 제29권2호
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    • pp.299-310
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    • 2008
  • Objectives : This study was performed to investigate the anti-fibrogenic effect of Salvia miltiorrhiza on rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells(HSC-T6) were treated with various concentrations of Salvia miltiorrhiza extract for 24 hours. It was extracted either with distilled water or 50% EtOH. After the treatment, cell viability, proliferation, procollagen levels and the mRNA of the collagen type 1a2 and ASMA were measured Results : The viability and proliferation of the hepatic stellate cells were decreased as concentration increased. The mRNA expression decreased consistently with the volume of the secreted procollagen with the extraction made with distilled water. This indicates the herb has inhibitory effect on fibrogenesis of the liver by regulating one of the fibrosis associated genes in transcription. However it increased in 50% EtOH extraction, which shows that a more stable reaction is expected of the extraction made with distilled water than the extraction made with 50% EtOH. The production of procollagen was decreased by a low-concentration treatment with Salvia miltiorrhiza, but increased by a high concentration. It seemed that the cells were responding to Salvia miltiorrhiza in low- concentration, thus producing smaller amounts of collagen. When the drug was administered in high enough concentration to give direct toxicity to cells, an overproduction of collagen was observed. Conclusion : These results suggest that Salvia miltiorrhiza is a possible candidate for the treatment of cirrhotic patients as well as for patients with chronic hepatitis when extracted with water in the proper concentrations.

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