• Title/Summary/Keyword: 반복투여

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Single-Dose Toxicity and Four Week Repeated-Dose Toxicity Study on Tensolin-F® (3,9-diferuloyl-6-oxopterocarpen) (Tensolin-F® (3,9-diferuloyl-6-oxopterocarpen)의 단회 독성시험 및 4주 반복투여 독성시험)

  • Kim, Keun-Su;Park, Sung-Min;Lee, Nam-Jin;Pyo, Hyeong-Bae;Chai, Hee-Yul;Jung, Yu-Ri;Lin, Chun-Mai;Kim, Sun-Hee;Lee, Hye-Young;Kang, Jong-Koo
    • Toxicological Research
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    • v.23 no.4
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    • pp.405-413
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    • 2007
  • This study was to investigate single and repeated-dose toxicities of Tensolin-$F^{(R)}$, an anti-wrinkle agent, in Sprague-Dawley (SD) rats or ICR mice. In single-dose oral toxicity study, the test materials were administered once by gavage to male and female SD rats at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and Tensolin-$F^{(R)}$ treated group. Therefore, the approximate lethal dose of Tensolin-$F^{(R)}$ was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test material was administered once daily by gavage to male and female ICR mice at dose levels of 0, 25, 50 and 100 mg/kg/day for 4-weeks. In the results, no abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, necropsy findings, histopathological findings. In hematological analysis, there was a trend of increase in reticulocyte at male 25 mg/kg, although such changes were in normal ranges. On the other hand, there was a trend of decrease in hemoglobin at female 50, 100 mg/kg, such changes were in normal ranges. In addition, serum biochemical parameters including sodium, BUN and chloride increased at 25, 50 and 100 mg/kg. Relative organ weights of right testis, brain, lung and left epididymis were increased in 100 mg/kg groups of male rats in contrast to not change in female groups. However, these changes of relative organ weights, hematological and serum biochemical parameters were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, 4-week repeated oral dose of Tensolin-$F^{(R)}$ to ICR mice did not cause apparent toxicological change at the dose of 25, 50, 100 mg/kg body weight. Consequently the no-observed-adverse-effect level (NOAEL) for Tensolin-$F^{(R)}$ in ICR mice following gavage for at least 4-week is higher than 100 mg/kg/day.

Repeated Dose and Reproductive/Developmental Toxicities of Acetanilide in Rats (랫드를 이용한 Acetanilide의 반복투여 및 생식/발생독성 병행시험)

  • Chung, Moon-Koo;Baek, Sung-Soo;Lee, Sang-Hee;Kim, Hyun-Mi;Choi, Kyung-Hee;Han, Sang-Seop
    • Toxicological Research
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    • v.23 no.4
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    • pp.391-403
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    • 2007
  • The study was conducted to assess the repeated dose and reproduction and developmental toxicities of acetanilide, an intermediate for drug production, as a part of OECD Screening Information Data Set (SIDS) program. The test agent was administered by gavage at dose levels of 0, 22, 67, 200 and 600 mg/kg to Sprague-Dawley rats (12/group/sex) during pre-mating and mating period for males(up to 30 days) and females and pregnancy and early lactation period for females (up to 39-50 days). At 22 mg/kg, decreases in HGB, HCT (males) and MCHC (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow (both sexes) were observed. At 67 mg/kg, salivation (males), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC (males), increases in MCV (males) and spleen weight (males), hyperplasia of spleen red pulp and femur bone marrow (both sexes) were observed. At 200 mg/kg, decreases in locomotor activity and salivation (both sexes), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and increases in MCV, MCH, BUN, T-BIL (males), enlargement of spleen (both sexes), increased weight of spleen (males), hyperplasia of spleen red pulp and femur bone marrow and extramedullary hematopoiesis of liver (both sexes), atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. At 600 mg/kg, decreases in locomotor activity, cyanosis (both sexes), reddish tear, and salivation (males), mortality (4 out of 12 females), decreased body weight (females), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC and increases in WBC, MCV, MCH, reticulocyte, neutrophil, lymphocyte, monocyte, AST, ALT, BUN, T-BIL, ALB, Ca and A/G ratio (males), enlargement of spleen, increased weights of spleen (both sexes), liver (males), kidney and ovary, decreased weights of thymus (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow and extramedullary hematopoiesis of liver (both sexes), and atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. Regarding the reproduction and development toxicities, there were no treatment-related changes in precoital time, mating index, fertility index and pregnancy index at all doses tested. At 22 and 67 mg/kg, there were no adverse effects on all the parameters observed. At 200 mg/ kg, decreased body weight of pups (day 4 p.p.) were observed. At 600 mg/kg, decreased body weight of pups (day 0 and 4 p.p.) and viability index (day 4 p.p.), increased incidence of newborns dead or with abnormal clinical signs were observed. The results suggest that the NOAELs for general toxicity are < 22 mg/kg, LOAELs are 22 mg/kg and the NOAELs for reproductive toxicity are 67 mg/kg.

Four-week Repeated Oral Toxicity Study of the Extract of Aralia elata in Rats (랫드에서 두릅 추출물의 4주 반복투여 독성시험)

  • Jin, Ju-Youn;Yang, Hee-Kyoung;Kim, Ji-Min;Ko, Mun-Su;Hong, Hyun-Ju;Jin, Young-Gun;Kim, Dong-Gun;Kim, Sang-Chul;Lee, Il;Hyon, Min-Kyong;Kang, Sang-Chul;Kim, Jae-Hoon;Lee, Young-Jae
    • Toxicological Research
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    • v.22 no.4
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    • pp.445-452
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    • 2006
  • Aralia elata, a common medicinal and culinary herb, has beer consumed for centuries without any reported adverse effects. However, due to its limited safety information, we decided to investigate the repeated-dose toxicity of ethanolic extract of Aralia elata. The test was administered once daily by the gavage to male and female rats at doses of 0, 250, 500 and 1,000 mg/kg/day for four weeks. Throughout the study, no treatment-related deaths or clinical signs were observed. Also, no apparent changes were detected in ophthalmoscopy, urinalysis, serum biochemistry, hematology and gross necropsy. The test result showed a significant decrease in body and heart weight of males treated with 250 mg/kg of extract of Aralia elata compared to normal control, a significant increase in relative brain weight and adrenal weight in females treated with 250 mg/kg of extract compared to normal control. However, all these changes were not considered toxicologically important due to irrelevant dose-response relationship to gross and microscopic findings. Histopathologically, abnormal changes were not observed in any target organs. On the basis of these results, the NOAEL of extract of Aralia elata was estimated to be more than 1,000 mg/kg/day under the tested conditions.

Modulation Effects of Antioxidant Vitamins on Ochratoxin A-induced Oxidative Toxicity in Mice (마우스에서 Ochratoxin A로 유발된 산화적 독성에 대한 항산화 비타민의 완화작용)

  • Park, Jung-Hyun;Kang, Sung-Jo;Kang, Jin-Soon;Ryu, Jae-Chun;Chung, Duck-Hwa
    • Korean Journal of Food Science and Technology
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    • v.31 no.3
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    • pp.831-837
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    • 1999
  • Ochratoxin A (OA), a naturally occurring mycotoxin, has been known to cause renal and hepatic lesion in human and animals. This study was carried out to investigate the modulation effects of antioxidant vitamins on OA-induced lipid peroxidation associated with oxidative damage. Vitamin C (10 mg/kg/day) and vitamin E (63.8 mg/kg/day) were administered by intraperitoneal (i.p.) injection to male ICR mice, and 1 hr later, OA which was dissolved in 0.1 M $NaHCO_3$, treated 4 mg/kg/day by i.p. injection. During 4 days repeated, and then measured superoxide dismutase (SOD) activity, catalase activity and malondialdehyde (MDA) formation in microsomes of liver and kidney. Additionally, the relationship between cell damage and modulation effects of antioxidant vitamins was evaluated by comet assay. Results were as followed; i) SOD, catalase activity and MDA level were significantly increased by OA treated, ii) SOD, catalase activity and MDA formation were significantly decreased by antioxidant vitamins combine treated, iii) blood cell damage associated with lipid peroxidation, induced by OA, also modulated by antioxidant vitamins. These results indicated that antioxidant vitamins might be used for prevention of renal and hepatic damage due to ochratoxicosis.

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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.

Helicobacter pylori Infection in Children with Recurrent Abdominal Pain (소아에서 만성 반복성 복통(Recurrent Abdominal Pain)과 Helicobacter pylori 감염과의 연관성에 대한 연구)

  • Na, So Young;Seo, Jeong Kee
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.8 no.1
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    • pp.1-11
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    • 2005
  • Purpose: The aim of this study was to evaluate the relationship between H. pylori infection and recurrent abdominal pain (RAP) in children and to evaluate the effects of eradication therapy on RAP. Methods: From January 1998 to January 2005, 166 children with RAP (61 male, 105 female) aged $10.0{\pm}3.3$ years were included. Upper gastrointestinal endoscopies were performed for all the patients. All H. pylori infected children (n=70) received the eradication therapy and were divided into two groups: Group Ia (n=52); eradicated, Group Ib (n=18); non-eradicated. H. pylori-negative children (n=96) were divided into three groups according to the medication: Group IIa (n=67); no medication, Group IIb (n=13); acid-suppressant, Group IIc (n=16); both acid-suppressant and antibiotics. Questionnaire for symptoms were asked at the first, 6th, 12th, 24th, and 36th months following the treatment (grade 0; completely resolved, grade 1; definitely improved, but there are occasional episodes of mild abdominal pain, grade 2; no change in the frequency and intensity of abdominal pain). Results: In about 90% of H. pylori positive children, RAP improved in the both H. pylori-eradicated and non-eradicated children in a follow-up survey. In about 75% of H. pylori-negative children, RAP also improved among in the three groups of patients regardless of medication. Conclusion: These results suggest that there was no correlations between improvement of RAP and eradication of H. pylori, and between improvement of RAP and medication. Consequently the reassurance that the children with RAP have no serious organic cause was important to improvement of RAP.

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Ischemic Preconditioning and Its Relation to Glycogen Depletion (허혈성 전처치와 당원 결핍과의 관계)

  • 장대영;김대중;원경준;조대윤;손동섭;양기민;라봉진;김호덕
    • Journal of Chest Surgery
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    • v.33 no.7
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    • pp.531-540
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    • 2000
  • Baclgrpimd; Recent studies have suggested that the cardioprotective effect of ischemic preconditioning(IP) is closely related to glycogen depletion and attenuation of intracellular acidosis. In the present study, the authors tested this hypothesis by perfusion isolated rabbit hearts with glucose(G) is closely related to glycogen depletion and attenuation of intracellular acidosis. In the present study, the authors tested this hypothesis by perfusion isolated rabbit hearts with glucose(G)-free perfusate. Material and Method; Hearts isolated from New Zealand white rabbits(1.5~2.0 kg body weight) were perfused with Tyrode solution by Langendorff technique. After stabilization of baseline hemodynamics, the hearts were subjected to 45 min global ischemia followed by 120 min reperfusion with IP(IP group, n=13) or without IP(ischemic control group, n=10). IP was induced by single episode of 5 min global ischemia and 10 min reperfusion. In the G-free preconditioned group(n=12), G depletion was induced by perfusionwith G-free Tyrode solution for 5 min and then perfused with G-containing Tyrode solution for 10 min; and 45 min ischemia and 120 min reperfusion. Left ventricular functionincluding developed pressure(LVDP), dP/dt, heart rate, left ventricular end-distolic pressure(LVEDP) and coronary flow (CF) were measured. Myocardial cytosolic and membrane PKC activities were measured by 32P-${\gamma}$-ATP incorporation into PKC-specific peptide and PKC isozymes were analyzed by Western blot with monoclonal antibodies. Infarct size was determined by staining with TTC(tetrazolium salt) and planimetry. Data were analyzed by one-way analysis of variance (ANOVA) and Turkey's post-hoc test. Result ; In comparison with the ischemic control group, IP significantly enhanced functional recovery of the left ventricle; in contrast, functional significantly enhanced functional recovery of the left ventricle; in contrast, functional recovery were not significantly different between the G-free preconditioned and the ischemic control groups. However, the infarct size was significantly reduced by IP or G-free preconditioning(39$\pm$2.7% in the ischemic control, 19$\pm$1.2% in the IP, and 15$\pm$3.9% in the G-free preconditioned, p<0.05). Membrane PKC activities were increased significantly after IP (119%), IP and 45 min ischemia(145%), G-free [recpmdotopmomg (150%), and G-free preconditioning and 45 min ischemia(127%); expression of membrane PKC isozymes, $\alpha$ and $\varepsilon$, tended to be increased after IP or G-free preconditioning. Conclusion; These results suggest that in isolated Langendorff-perfused rabbit heart model, G-free preconditioning (induced by single episode of 5 min G depletion and 10 min repletion) colud not improve post-ischemic contractile dysfunction(after 45-minute global ischemia); however, it has an infarct size-limiting effect.

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Antihyperglycemia Effect of Medicinal Plants Mixture in Streptozotocin-Induced Diabetic Rats (Streptozotocin 유발 당뇨쥐에서 항당뇨 생약 복합물의 혈당강하 효과)

  • Park, Keum-Ju;Jin, Hwi-Seung;Park, Seung-Hee;Kim, Eun-Ho;Kim, Jae-Ki
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.12
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    • pp.1554-1559
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    • 2008
  • This study was performed to investigate the hypoglycemic effect of single and repeated oral administration of medicinal herbal mixture (AD) in streptozotocin (STZ) induced diabetic rats. Angelica decursiva, Lycium chinense and Adenophora triphylla var. japonica Hara were selected by oral glucose tolerance test (OGTT) and mixed for AD mixture. In an oral glucose tolerance test, the AD inhibited the increase in blood glucose levels at 1 hr and 2 hr and decreased incremental glycemic response area under the curve. In a single administration of AD1 (100 mg/kg) and AD2 (500 mg/kg), significant reductions by 5.3% and 12.3% were observed in fasting blood glucose level for 4 hours. During the 1 month of the experimental period, AD1 and AD2 was given to the STZ induced diabetic rats. At 4th week, the fasting blood glucose levels of AD1 and AD2 caused a fall of 25.5% and 37.9%, respectively. In addition, the body weights were decreased by 7.7% (AD1) and 1.7% (AD2), respectively, compared with diabetic control (DC, decreasing of 10.2%). This study suggests that AD could be potentially useful for fasting and post-prandial hyperglycemia treatment and all these effects concluded to the use of this plant extract to manage diabetes mellitus.

Mixture of Extracts of Cynanchum wilfordii and Phlomis umbrosa Turcz. Does Not Have an Estrogenic Effect in Ovariectomized Rats (백수오와 한속단 추출물의 비에스트로젠 효과에 관한 연구)

  • Han, Song-Hee;Lee, Tae-Hee;Jang, Ja-Young;Song, Hyun-Kyung;Hong, Sang-Keun;Kim, Yu-Ri;Han, Beom-Seok
    • Korean Journal of Food Science and Technology
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    • v.47 no.5
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    • pp.667-672
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    • 2015
  • Cynanchum wilfordii and Phlomis umbrosa Turcz. are known to contain isoflavone, a representative phytoestrogen. This study was performed to determine whether the extract mixture of C. wilfordii and P. umbrosa Turcz. would induce an estrogenic effect in ovariectomized rats. The extracts were administered to the ovariectomized rats at 30, 60, 120 mg/kg per day for 4 weeks, respectively. They showed no estrogenic effect, which was indicated by the decrease in uterus wall thickness as well as the increase in body weight and the level of cholesterol and triglyceride. The extracts also had no effect on the concentrations of estrogen and growth hormone in the serum. However, the increase in alkaline phosphatase activity, which leads to protection against the bone loss caused by ovariectomy, was noted on administration of the extract. Therefore, it seemed that the extracts of C. wilfordii and P. umbrosa Turcz. had no estrogenic effect in rats.

Characterization of Biomass-Based Foam Structures for Home-Meal-Replacement Containers (가정간편식 용기용 바이오매스 기반 발포구조체의 특성에 관한 연구)

  • Kim, Inae;Kim, Sumin;Kambiz, Sadeghi;Han, Jeonggu;Hwang, Kiseop;Kwon, Hyukjoon;Kim, Yongsu;Yoo, Seung Ran;Seo, Jongchul
    • KOREAN JOURNAL OF PACKAGING SCIENCE & TECHNOLOGY
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    • v.26 no.2
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    • pp.77-83
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    • 2020
  • A series of foamed plastic sheets containing biomass (as HMR container) were developed via different foaming process temperatures, and their density, porosity, WVTR, and pore morphology were evaluated. Thermal stability of samples during re-heating the food in oven, change in morphology, density, porosity, and WVTR were investigated using a simulated thermal shock process according to MIL-STD-883E assay. As such, the pore size of samples was generally increased with increasing temperature of the foaming process. It can be explained that as foaming temperature increased, the viscosity of molten resins and the repulsive force against pore expansion decreased. In addition, an increase in the thermal shock cycle reduced the pore size and WVTR, while density increased because high temperature treatment that softened the sheet matrix was followed by a low temperature incubation, which contracted the matrix, thereby changing the physical and morphological properties of samples. However, an insignificant change in density was observed and WVTR tended to be decreased, indicating that as-prepared foamed plastic sheets could be used as a high thermal stable container for HMR application. Therefore, it found that the properties of newly developed HMR containers containing biomass were dependent on the foaming process temperature. Moreover, to better understanding of these newly developed containers, further investigations dealing with foaming process temperature based on various food items and cooking conditions are needed.