• Title/Summary/Keyword: Acute and repeated toxicity

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Safety Evaluation of Korean Mistletoe Extract (한국산 겨우살이 추출물의 안전성 평가)

  • Kim, Inbo;Jeong, Ju-Seong;Yoon, Taek Joon;Kim, Jong Bae
    • The Korean Journal of Food And Nutrition
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    • v.26 no.3
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    • pp.383-390
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    • 2013
  • Mistlero C was shown to be non-genotoxic in a series of genotoxicity tests, including a bacterial reverse mutation test and a combined in vivo mammalian erythrocyte micronucleus test. In a bacterial reverse mutation assay, no significant increases in the number of revertant colonies, compared to the negative control, was detected in $5,000{\mu}g/plate$ of Mistlero C. In addition, with Mistlero C, no changes were shown in the number of micronucleated polychromatic erythrocytes (MNPCE) among 2,000 polychromatic erythrocytes compared to the negative control. Mistlero C was administered orally in rats to investigate acute toxicity. The $LD_{50}$ values in rats were above 2,000 mg/kg. In a repeated dose, 13-week, oral toxicity study conducted in rats, no compound-related adverse effects were shown at doses of Mistlero C of up to 1,000 mg/kg body weight/day. The results of these studies support the safe use of Mistlero C in food for human consumption.

In Vivo Effects of Lead on Erythrocytes Following Chronic Exposure through Drinking Water

  • Lee, Moo-Yeol;Shin, Jung-Hun;Han, Hee-Shim;Chung, Jin-Ho
    • Archives of Pharmacal Research
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    • v.29 no.12
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    • pp.1158-1163
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    • 2006
  • More than 95% of lead, a environmental heavy metal, entering into blood accumulates in erythrocytes suggesting erythrocytes as an important target of lead toxicity. Recent studies reported that erythrocytes could contribute to blood coagulation via phosphatidylserine (PS) exposure in erythrocytes. However, in vivo effects of chronic lead exposure especially by drink-ing water on procoagulant activity of erythrocytes have not been studied yet. In the present study, we investigated the effects of chronic exposure of lead by drinking water on erythrocytes in rats. Groups of 40 male rats were provided with drinking water containing various concentrations of lead for 4 weeks and complete blood cell count, procoagulant activities of erythrocytes and platelets were evaluated with basic inspections on body weight and food/water consumption. The administration of lead containing drinking water increased the blood lead level (BLL) in a dose-dependent manner up to $22.39{\pm}2.26\;{\mu}g/dL$. Water consumption was significantly decreased while food consumption or body weight gain was not affected. In contrast to the previous findings with acute lead exposure, chronic lead exposure failed to increase PS exposure in erythrocytes with statistical significance although some trends of enhancement were observed. It implies that a certain adaptation might have happened in body during repeated exposure to lead, resulting in attenuation of PS exposure. With this study, we believe that a valuable information was provided for the study on the toxicological significance and the risk assessment of lead contaminated drinking water.

Experiment on the effect of Artemisia sieversiana extract on hair loss prevention and cell growth

  • Yang, Seungbo;Jin, Chul;Kwon, Seungwon;Cho, Seung-Yeon;Park, Seong-Uk;Jung, Woo-Sang;Moon, Sang-Kwan;Park, Jung-Mi;Cho, Ki-Ho;Ko, Chang-Nam
    • The Journal of Korean Medicine
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    • v.43 no.1
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    • pp.18-32
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    • 2022
  • Objectives: This study aimed to examine the safety, effects on proliferation of hair papilla cells, and anti-inflammatory and antioxidant mechanisms of Artemisia sieversiana Ehrh. ex Willd. (AS) extract. Methods: Safety tests through purity testing, acute toxicity tests, and repeated toxicity tests were performed using AS extract (ASE) which had been dried for over two years. Cell culture and proliferation tests were conducted; VEGF (vascular endothelial growth factor), bFGF (basic fibroblast growth factor), and EGF (epidermal growth factor) and protein expression analyses were performed for mechanistic evaluation; and inhibitory effects of ASE on the RNA expression of testosterone, 5𝛼-reductase, and aromatase was assessed. The anti-inflammatory and antioxidant efficacy of ASE was confirmed by measuring the levels of nitric oxide, inflammatory mediators (TNF-𝛼 and PGE2), inflammatory cytokines (IL-1𝛽, IL-6, and IL-8), and chemokine MCP-1. Results: The safety of ASE was confirmed. The mechanism of cell proliferation in human hair follicle dermal papilla cells involved the promotion of VEGF, bFGF, and EGF expression. ASE decreased mRNA expression of testosterone, 5𝛼-reductase, and aromatase-1 in a concentration-dependent manner. PGE2 and TNF-𝛼 production by inflammatory mediators was also significantly decreased in a concentration-dependent manner, and inflammatory cytokine and chemokine expression was inhibited. Conclusions: ASE is suggested to promote papillary cell growth at the cellular level, to suppress expression of various enzymes involved in hair cycle and cell death, and to inhibit hair loss through anti-androgen, anti-inflammatory, and antioxidant effects.

Combined Modality Treatment in Nasopharyngeal Carcinoma (비인강암의 병합요법)

  • Yun, Sang-Mo;Kim, Jae-Cheol;Park, In-Kyu
    • Radiation Oncology Journal
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    • v.19 no.2
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    • pp.100-106
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    • 2001
  • Purpose : We performed a retrospective analysis to compare short term results of induction chemotherapy-radiotherapy versus concurrent chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma. Materials and Methods : From Oct. 1989 to May 1998, 62 patients with locally advanced nasopharyngeal carcinoma were treated with induction chemotherapy followed by radiotherapy (induction group) or concurrent chemo-radiotherapy (concurrent group). Induction chemotherapy was done for 50 patients, and concurrent chemotherapy for 12 patients. Age, sex, performance status, and pathologic types were evenly distributed between two groups. Stage distribution showed $32\%$ with IIB, $32\%$ with III, and $38\%$ with IV in induction group, and $50\%,\;33.3\%,\;and\;16.7\%$ in concurrent group, respectively. Chemotherapy regimen was CF (cisplatin and 5-FU) in both groups, and drug delivery method also same. Cisplatin $100\;mg/m^2$ was intravenously infused on day 1, and 5-FU $1,000\;mg/m^2$ on day $2\~6$. This was repeated at 3 weeks interval. At the end of radiotherapy, total cycles of chemotherapy were $1\~3$ (median 2) in both groups. Conventionally fractionated radiotherapy with daily fraction size $1.8\~2.0\;Gy$ and 5 fractions/week was done. Total dose was $69.4\~86\;Gy$(median 73.4 Gy) for induction group, and $69.4\~75.4\;Gy$ (median 70.8 Gy) for concurrent group. Follow-up time was $9\~116$ months (median 40.5 months) for induction group, $14\~29$ months (median 21 months) for concurrent group, respectively. Results : Overall 2 year survival rate (2YSR) for all patients was $78.7\%$. According to treatment modality, 2YSR were $77\%$ for induction group, $87\%$ for concurrent group (p>0.05). 2 year disease-free survival rate were $56\%$ and $81\%\;(p>0.05)$, respectively. Complete response to treatment were $75.5\%$ for induction group and $91.7\%$ for concurrent group, but there was no statistical difference. The incidence of grade $3\~4$ hematologic toxicity during radiotherapy was not differ between two groups, but grade 2 leukopenia was more frequent in concurrent group $(18\%\;vs\;66.7\%)$Grade $3\~4$ mucositis was more frequent in concurrent group $(4.0\%\;vs\;33.3\%)$. Overall incidence of grade $3\~4$ acute toxicity during radiotherapy was more frequent in concurrent group $(6.0\%\;vs\;41.7\%,\;p=0.005)$. Conclusion : Concurrent chemo-radiotherapy showed a trend of improvement in short-term survival and in treatment response when compared with induction chemotherapy-radiotherapy in locally advanced nasopharyngeal carcinoma. More controlled randomized trial are needed.

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