• 한국식품영양과학회지
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• 제31권5호
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• pp.910-916
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• 2002

생약재의 식품ㆍ생물 산업적 이용증대에 따라 생약재의 안전한 위생화 기술이 요구되고 있다 본 연구에서는 생약재의 위생화 기술로서 방사선 조사기법의 활용 가능성을 검토하기 위하여, 감마선을 조사한 생약재 3종에 대한 유전독성학적 안전성을 평가하고자 하였다. 공시 재료는 오염유기체 완전 구제선량인 10 kGy의 감마선을 조사시킨 황기, 백출 및 승마로 하였으며, 각각의 열수 추출물의 유전독성을 in vitro 시험으로 평가하였다. 유전독성 평가는 Salmonella typhimurium TA98 및 TA100 균주를 이용한 복귀 돌연변이 시험(Ames test)과 Chiilese hamster ovary(CHO) 세포를 이용한 in vitro 소핵 유발 시험으로 시행하였다. 각각의 시험은 59 nix를 첨가한 대사 활성화 시스템과 첨 가하지 않은 비활성화 시스템으로 구분하여 실시하였으며, 시료의 최고 처리 농도는 복귀돌연변이 시험에서는 5mg/plate로, 소핵유발시험에서는 50%의 세포증식 억제를 나타내는 농도(1 mg/mL)로 하였다. 복귀 돌연변이 시험 결과 대사 활성화 및 비활성화의 경우 모두에서 각 시료에 의한 복귀변이 집락수의 증가를 인정할 수 없었으며, 각 용량단계에서 감마선 조사군과 비조사군 간의 차이도 볼 수 없었으므로 음성으로 판정하였다. 소핵 유발시험에서도 음성 대조군 및 감마선 조사군과 비조사군 모두 각 용량 단계에서 세포 내에 생성된 소핵의 빈도가 3% 이하로 나타남에 따라, 시료에 의한 소핵의 유발을 인정할 수 없었으므로 음성으로 판정하였다 따라서 감마선이 조사된 각각의 시료는 직접 및 간접 돌연변이원으로 작용하지 않으며 세포유전 독성을 나타내지 않음을 확인할 수 있었다. 향후, 생체내 유전독성 시험, 만성독성 시험 및 생식독성 시험 등의 추가적인 in vivo실험이 행하여진다면 감마선 조사 생약재의 안전성을 보다 명확히 밝힐 수 있을 것으로 생각된다.

• 환경생물
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• 제21권1호
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• pp.36-41
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• 2003

연안지역의 환경오염 및 양식용수의 이용과정에 파생될 수 있는 구리의 오염에 따른 넙치의 생존, 대사율, 사료효율 및 성장율에 미치는 구리의 영향을 검토하였다. 4개의 아치사구리 농도(50, 80, 180, 320 $\mu\textrm{g}$ L$^{-1}$)에서 6주동안 실험하였다. 실험기간 동안 넙치는 대조구에서는 실험종료시 까지 사망개체가 전혀 나타나지 않아 100%의 생존율을 나타내었다. 구리 노출농도 180 $\mu\textrm{g}$ L$^{-1}$에서는 노출 4주부터 감소하기 시작하였으며, 노출기간이 길어짐에 따라 지속적으로 감소하여 노출 6주에는 84.0%까지 감소하였다. 또한 구리 노출농도 320 $\mu\textrm{g}$L$^{-1}$에서 노출 2주부터 감소하여 노출 6주에 82.0%로 높은 두 개의 농도구에서 유의한 감소가 나타났다. 산소 소비량은 노출농도 180, 320 $\mu\textrm{g}$ L$^{-1}$에서 대조구보다 각각 27.0, 42.0%가 저하하여 유의한 감소를 나타냈다. 사료효율은 대조구가 43.6%로서 가장 높은 효율을 나타냈고, 노출농도가 320 $\mu\textrm{g}$ L$^{-1}$에서는 30.0%로서 가장 낮은 성장 상태를 보였으며, 노출농도 80 $\mu\textrm{g}$ L$^{-1}$이상에서는 대조구에 비해 유의한 감소를 나타냈다. 성장율은 대조구에서 평균 16.8%로 나타나 가장 높은 성장을 보였으며, 노출농도 320 $\mu\textrm{g}$ L$^{-1}$에서는 5.4%로서 가장 낮은 성장을 보였다. 성장률의 전체적인 양상은 노출농도가 증가할수록 성장이 떨어지는 결과를 보였으며, 사료효율과 마찬가지로 노출농도 80 $\mu\textrm{g}$ L$^{-1}$ 이상에서 유의한 감소를 나타냈다.

• 대한약리학회지
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• 제21권1호
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• pp.34-48
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• 1985

항균제 nitrofurantion에 의한 폐독작용의 생화학적 기전을 규명하기 위한 연구 일환으로 in vitro에서 폐장 microsome 지질의 과산화 및 반응성 산소 radical $(O^{-}_{2}{\cdot},\;H_2O_2,\;OH{\cdot},\;^1O_2)$의 생성에 대한 nitrofurantion의 영향과 양자 간의 상호 관련성을 검토하였다. Nitrofurantion은 호기성 반응 조건에서 돼지 폐장 microsome의 NADPH 의존성 지질 과산화를 용량 의존적으로 증가시킬 뿐 아니라 $O^{-}_{2}{\cdot},\;H_2O_2$ 및 두 radical의 상호 작용으로 2차적으로 형성되는 $OH{\cdot}$의 생성 또한 촉진하였으며 $^1O_2$생성은 관찰되지 않았다. 이와 같은 폐장 microsome지질 과산화 증가는 SOD 및 catalase에 의하여 억제될 뿐만 아니라 $OH{\cdot}$ 제거 물질인 mannitol, thiourea에 의하여도 현저히 억제되었으며, $^1O_2$ 제거 물질에 의하여는 영향을 받지 않았던 한편 염기성 반응 조건에서는 nitrofurantoin에 의한 지질 과산화가 관찰되지 않았다. 이상의 결과로 미루어 보아 nitrofurantoin은 폐장 microsome의 NADPH 의존적이 반응성산소 radical $(O^{-}_{2}{\cdot},\;H_2O_2$ 및 $OH{\cdot})$의 생성을 증가시키며 이들 중 특히 $OH{\cdot}$ 에 의한 microsome막 지질 과산화를 촉진하는 것으로 결론지었고, 이와 같은 in vivo 현상은 nitrofurantion의 in vitro 폐독작용의 기전을 설명하는 일부가 될 것으로 사료하였다.

• Radiation Oncology Journal
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• 제31권4호
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• pp.206-215
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• 2013

Purpose: Re-irradiation (re-RT) is considered a treatment option for inoperable locoregionally recurrent head and neck cancer (HNC) after prior radiotherapy. We evaluated the efficacy and safety of re-RT using Helical Tomotherapy as image-guided intensity-modulated radiotherapy in recurrent HNC. Materials and Methods: Patients diagnosed with recurrent HNC and received re-RT were retrospectively reviewed. Primary endpoint was overall survival (OS) and secondary endpoints were locoregional control and toxicities. Results: The median follow-up period of total 9 patients was 18.7 months (range, 4.1 to 76 months) and that of 3 alive patients was 49 months (range, 47 to 76 months). Median dose of first radiotherapy and re-RT was 64.8 and 47.5 $Gy_{10}$. Median cumulative dose of the two courses of radiotherapy was 116.3 $Gy_{10}$ (range, 91.8 to 128.9 $Gy_{10}$) while the median interval between the two courses of radiation was 25 months (range, 4 to 137 months). The response rate after re-RT of the evaluated 8 patients was 75% (complete response, 4; partial response, 2). Median locoregional relapse-free survival after re-RT was 11.9 months (range, 3.4 to 75.1 months) and 5 patients eventually presented with treatment failure (in-field failure, 2; in- and out-field failure, 2; out-field failure, 1). Median OS of the 8 patients was 20.3 months (range, 4.1 to 75.1 months). One- and two-year OS rates were 62.5% and 50%, respectively. Grade 3 leucopenia developed in one patient as acute toxicity, and grade 2 osteonecrosis and trismus as chronic toxicity in another patient. Conclusion: Re-RT using Helical Tomotherapy for previously irradiated patients with unresectable locoregionally recurrent HNC may be a feasible treatment option with long-term survival and acceptable toxicities.

• Journal of Preventive Medicine and Public Health
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• 제24권3호
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• pp.287-304
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• 1991

Tolerance to several toxic effects of cadmium, including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicityandrenaltoxicity. Three groups of rats (A, B, C), each consisting of 16 rats, were studied and each group was divided into four subgroups (1, 2, 3, 4), 4 rats for each subgroup. Rats were subcutaneously pretreated with saline (A), $CdCl_2$ (0.5 mg/kg, B), and $ZnCl_2$ (13.0 mg/kg, C) during time periods of $1{\sim}6$ weeks. At the end of the period, rats were challenged with $CdCl_2$ (3.0, 6.0 and 9.0 mg/kg, ip). After giving the challenge dose, cadmium and metallothionein (MT) concentrations were determined and also observed the histologic change in liver and kidney. The concentration of cadmium in liver and kidney increased dose-dependently to the challenge dosage. These da indicate the kidney is a major target organ of chronic cadmium poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play an important role in the nephrotoxicity observed in response to long-term exposure to cadmium. In addition, histologic examination of group $A_2,\;A_3\;and\;A_4$ revealed moderate to severe cadmium toxicity, evidenced by infiltration of inflammatory cells, cell swelling, pyknosis, enlarged sinusoids and necrosis in liver, and tubule cell necrosis and degeneration in kidney. However, MT concentrations in liver and kidney were increased by the pretreatment of $CdCl_2$ and $ZnCl_2$, and their morphological findings were not significantly changed, comparing with control group. Higher MT concentration in liver and kidney observed in the pretreated groups constitutes a plausible explanation of the protective effects of pretreatment against the cadmium toxicity after challenge dosing.

• 대한한의학회지
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• 제20권3호
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• pp.45-53
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• 1999

Since Radix Stemonae was recorded hypothennal and a little toxic in the 'Myngyubelrok (名醫別錄)', it has been recorded as having the same nature in many herbal books. However, the security of Radix Stemonae when used to treat respiratory disease over a long term has not been studied until now. Therefore, the objective of this study is to determine the effects of Radix Stemonae on the main organs if Radix Stemonae is administrated over a long term. In order to investigate the histological changes of the liver and kidneys of rats after oral administration of Radix Stemonae extract, the experimental rats were subdivided into control, 1, 3, 5, 7, 21, 28 and 35 days after administration groups, and 10 rats per group were used in this study. The control group was sufficiently supplied with water and solid forage. The other groups were administrated the reagent at 5mg/kg once a day by oral injection. Several times each day, the experimental groups were carefully observed for any changes of general condition, toxic symptoms, activity, appearance and the number of dead rats. The experimental groups were weighed and narcotized. For the histological observation, the tissues of liver and kidneys of the experimental groups were collected, stained by hematoxylin-eosin stain, and evaluated by observing the changes of gross appearance and by observing microscopic findings. 1. This drug, during the experimental term, did not induce any toxicological effect in mortality, abnormal symptoms or changes of body weight except for the 1 day after administration groups whose body weights were decreased, compared to the control group. 2. No gross changes of the liver and kidneys were observed in this study. 3. No histological changes of the liver were detected in 1 day after administration groups. However, dilation of the central vein was observed in 3, 5 and 7 days after administration groups and chronic passive congestion of the liver was demonstrated in the 21 days after administration groups. In the 28 and 35 days after administration groups, a centrolobular disposition of fatty tissue (adipose cell) was observed. 4. No histological changes of the kidneys were observed in this study. It is evaluated that if Radix Stemonae is administrated for a long term, it induces toxicity in the liver. So, to examine the toxicity of Radix Stemonae on the liver and kidney, it is necessary that the studies of biochemistry and electron microscopic findings about Radix Stemonae be systematically performed.

• 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.

• 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.

• 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 $88{\sim}102u$와 $164{\sim}200u$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.

• 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.