• 대한한방부인과학회지
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• 제26권1호
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• pp.59-68
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• 2013

Objectives: This study was conducted to investigate the acute toxicity of Pyungwi-san(Pingwei-san in Chinese) in ICR mice, according to KFDA and OECD guideline. Methods: In the present study, 15 male and female ICR mice administrated singly by gavage at dose levels of 0 and 2000 mg/kg of Pyungwi-san. During the experimental period, no treatment-related death was observed. There were no adverse effects on clinical signs, body weight, and gross findings at all treatment groups. Results: These results showed that the single oral adminstration of Pyungwi-san (Pingwei-san) did not cause any toxic effect at the dose levels of 2000 mg/kg in rats. Conclusions: Taken together, the median lethal dose($LD_{50}$) of Pyungwi-san (Pingwei-san) was considered to be over 2000 mg/kg body for both sexes.

• Toxicological Research
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• 제17권
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• pp.329-333
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• 2001

Apoptosis is the normal physiological process of cell death essential for the maintenance of homeostasis. The function of nicotinamide adenine dinucleotide (NAD) and adenine diphosphate (ADP) ribosylation (transfer of ADP-ribose to proteins) reactions in modifying apoptosis have recently been of great interest. Recently. CD38. a type 2 transmembrane glycoprotein expressed in hematopoietic and non hematopoietic cell lines. has been reported to possess NAD glycohydrolase activity (Han. 1999) and PC-1 and CD38 NADase regulates T cells by inhibition of phosphodiesterase/pyrophosphatase activity of PC-1 by its association with glycosaminoglycan (Hozada et al., 1999). Sindhuphak et al. (2000) has reported that cervical cancer cells can be differentiated from normal cells by using FTIR (Fourier-Transformed Infrared) technique. which has characterized shifts to be due to the phosphodiester bond in nucleic acid. protein amide I&II. carbohydrate and glycogen bands. Mechanisms how phosphodiester bond shift in cervical cancer cells as compared to control cells remain to be elucidated. Suramana et al. (2000) as well as Lohitnavy and Sinhaseni (1998) have studied methomyl and colchicine effects in rat splenocytes. Lactate Dehydroge-nase Isozymes 3 (LDH3) and LDH4 were observed to increase transiently and subsided in plasma of rats exposed to 6~8 mg/kg methomyl after 48 hours. Phosphodiester bond shift of nucleic acid. detected by FTIR. was also reported (Suramana et al., 2000). We report here, after analysis of bond shift patterns. a similar bond shifts detected by FTIR spectrum observed in human cervical cells and splenocytes of rats exposed orally to 2~8 mg/kg methomyl as well as rats exposed to colchicine 2~6 mg/kg orally.

• Toxicological Research
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• 제22권2호
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• pp.117-126
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• 2006

This study was conducted to obtain the acute information of the oral dose toxicity of lyophilized water extract of Picrorrhiza Rhizoma (PR) - dried underground stem of Picrorrhiza kurroa, having various pharmacological effects, in male and female mice. In order to calculate 50% lethal dose ($LD_{50}$), approximate lethal dose and target organs, test article was administered once by oral gavage to male and female ICR mice at 2000, 1000, 500 and 250 mg/kg. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing with organ weight and histopathology of 12 types of principle organs. As the results, we could not find any mortality, clinical signs, changes in the body weight and gross findings except for hair loss, a significantly (p<0.05) increase of body weight gains in 2000mg/kg of PR extracts-dosing male group and some sporadic gross findings. In addition, no meaningful changes on the organ weight and histopathology of 12 types of principle organs were detected in the present study except for significantly (p<0.05) but dose independent changes on thymus, spleen and popliteal lymph nodes weights, and some sporadic accidental histopathological findings. The results obtained in this study suggest that the PR extract is non-toxic in mice and is therefore likely to be safe for clinical use. The $LD_{50}$ and approximate lethal dose of PR extracts in both female and male mice were considered as over 2000 mg/kg.

• Toxicological Research
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• 제16권4호
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• pp.269-274
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• 2000

Epoxidised soya bean oil (ESBO, 1000, 2000 or 4000 mg/kg) was orally administered to BALB/c mice daily for 28 consecutive days, and the control mice were exposed to vehicle (corn oil). Mice were immunized and challenged with sheep red blood cells (SRBC) or bovine serum albumin (BSA). In groups exposed to ESBO, the body weight gains and the relative lymphoid organ weights were not significantly changed as compared with control group. Secondary IgG antibody response to BSA was not significantly changed by ESBO, but plaque-forming cell (PFC) response to SRBC was significantly suppressed in mice treated with 4000 mg ESBO/kg/day. The mitogenic response of splenic B cells induced by LPS was not effected by ESBO in any of the groups. These results indicate that ESBO did not induce significant humoral immune response at a dose less than 2000 mg/kg/day in mice.

• 동의생리병리학회지
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• 제23권5호
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• pp.993-1002
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• 2009

The object of this study was to evaluate the single dose toxicity of Taeumjowui-tang(TUJWT), a polyherbal formula have been traditionally used as prevention or treatment agent for obesity, in male and female mice. Aqueous extracts of TUJWT (Yield = 10.5%) was administered to female and male ICR mice as an oral dose of 2000, 1000 and 500 mg/kg (body wt.) according to the recommendation of KFDA Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy, organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, and changes in the body and organ weight except for diarrhea restricted in TUJWT 2000 mg/kg treated one male mouse at 1 day after administration, and increases of popliteal lymph node weights in all TUJWT administered groups. In addition, no TUJWT-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for increases of the frequency of hypertrophy and hyperplasia of lymphoid cells in the popliteal lymph nodes in all TUJWT treatment groups with some sporadic accidental findings. These increases of popliteal lymph node weights with hypertrophy and hyperplasia of lymphoid cells were considered that related to the immune modulate effect of TUJWT not toxicological signs. The results obtained in this study suggest that the TUJWT does not cause any toxicological signs. The 50% lethal dose and approximate lethal dose of TUJWT aqueous extracts in both female and male mice were considered as over 2000 mg/kg.

• Toxicological Research
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• 제22권4호
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• pp.431-438
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• 2006

The object of this study was to obtain acute toxicity information (single oral dose toxicity) of lyophilized water extract of Puerariae Radix (PR) in both male and female mice. In order to investigate the 50% lethal dose $(LD_{50})$, approximate lethal dosage (ALD), test substances were once orally administered to female and male ICR mice at dose levels of 2000 and 0 (control) mg/kg (body wt.) according to the recommendation of KFDA Guidelines [2005-60, 2005]. The mortality and body weight changes, clinical signs and gross observation were monitored during 14 days after dosing. Organ weight and histopathology of 12 principal organs were measured. As the results, we could not find any mortality, clinical signs, body weight changes and gross findings except for PR extracts unrelated sporadic findings. In addition, no abnormal changes related PR extracts treatment on the organ weight and histopathology of principal organs were detected except for some sporadic findings including hyperplasia of lymphoid follicles in the popliteal lymph nodes and spleen as pharmacological effects of PR extracts. The results obtained in this study suggest that the PR extracts does not cause any toxicological signs except for pharmacological effects of enhancement of Immune system. The $LD_{50}$ and ALD of PR extracts in both female and male mice were considered as over 2000 mg/kg because no mortalities were detected up to 2000mg/kg that was the highest dose recommended by KFDA and Organization for Economic Co-Operation and Development.

• 대한본초학회지
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• 제28권2호
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• pp.61-65
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• 2013

Objectives : Samchulgeonbi-tang (shenzhujianpi-tang) has been prescribed as one of traditional herbal medicine for treatment of stomach diseases since ancient time in Korea. Samchulgeonbi-tang extract was fermented by Lactobacillus spp. for improving the effect. However, the toxicity and safety of fermented Samchulgeonbi-tang (FS) extract were not confirmed. Therefore, this study was performed to evaluate the acute toxicity and safety of FS extract. Methods : To evaluate the acute toxicity and safety of FS extract, several doses of FS extract, 0, 500, 1000 and 2000 mg/kg, were orally administered to 20 male and 20 female ICR mice, respectively. After treatment with FS extract, we observed mortality, general toxicity, behavior and change of body weight for the 14 days. After 14 days of oral administration, all mice were sacrificed and hematological parameters were analyzed from blood serum. Results : In present study, the toxic signs such as mortality or abnormal behaviors by FS extract were not observed. There are no significant differences between FS-treated group and control group in body weight, organ weights, and hematological parameters. Conclusions : The remarkable adverse effects by FS extract were not observed in ICR mice. Also, any death was not occurred at all treated FS doses, 500, 1000 and 2000 mg/kg. Therefore, the approximate lethal dose (ALD) of FS extract may be more than 2000 mg/kg.

• 약학회지
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• 제44권6호
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• pp.572-577
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• 2000

The effects of ibuprofen on bioavailability of ciprofloxacin were studied in rabbits. Animals were divided into three groups ; group A received 60 mg/kg of ciprofloxacin; group B and C received 60 mg/kg of ciprofloxacin with 60 and 240 mg/kg of ibuprofen, respectively. Ciprofloxacin and ibuprofen were given by single oral administration. Serum concentrations of ciprofloxacin were measured by high performance liquid chromatography with UV detector and pharmacokinetic parameters were calculated. Area under the serum concentrations versus time curve (${\pm}\;S.E.$) of ciprofloxacin were decreased in group B and C compared with group A ($12.26\;{\pm}\;0.94$ and $12.57\;{\pm}\;0.94$ vs. $15.71\;{\pm}\;1.06\;{\mu}g{\cdot}hr/ml$, p<0.05), whereas total clearances were increased ($1.81\;{\pm}\;0.13$ and $1.76\;{\pm}\;0.12$ vs. $1.40\;{\pm}\;0.09\;l/hr/kg$, p<0.05). No significant differances in these parameters were observed between group B and C. Relative bio-availability of group B and C to group A were 78 and 80%, respectively. These results suggest that the coadministration of ibuprofen with ciprofloxacin may reduce the bioavailability of ciprofloxacin.

• Radiation Oncology Journal
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• 제18권4호
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• pp.329-336
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• 2000

목적 : 마우스 간암에서 방사선과 각종 항암제와의 복합요법을 시행하여, 방사선 감수성을 증가시킬 수 있는 약물을 탐색하고자 하였다. 방법 : C3H/HeJ마우스에 마우스 간암인 HCa-1을 이식하고, 평균 직경 8 mm에 이르렀을 때, 방사선 조사(25 Gy), 항암 약물(5-Fu, 150 mg/kg; adriamycln, 8 mg/kg; paclltaxel, 40 mg/kg; gemcltablne, 50 mg/kg), 또는 방사선과 항암 약물의 복합 치료를 시행하였다 치료에 대한 종양 반응은 종양 성장 지연과 항진 요인으로 분석하였다. 항진 효과를 보인 약물에 대하여 그 기전 연구는 조직 절편에서 apoptotic 수준을 평가하고, 또한 조절물질의 발현을 분석하였다. p53, Bcl-2, Bax, Bcl-XL, Bcl-XS, p21$^{WAF1/CIP1}$의 발현 분석은 westeblotting으로 하였다. 결과 : Gemcltabine 만이 방사선 감수성을 증가시키는 것으로 나타났다(항진요인:1.6). Gemcltabine과 방사선의 복합 치료는 apoptosis 유도에서는 부가적 수준만을 보였다. 조절울질의 발현 양상은 방사선 단독에 비하여 방사선과 gemcitabine의 병용시 p21$^{WAF1/CIP1}$의 증가가 유의하게 관찰되었다. 결론 : Gemcitabiue은 마우스 간암에서 방사선 감수성을 증가시키는 것으로 나타났다. 이를 조절하는 요소로서 p21$^{WAF1/CIP1}$ 이 관여할 것으로 생각 된다.

• Toxicological Research
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• 제16권2호
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• pp.163-172
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• 2000

Recently, there is a worldwide concern that a great number of man-made chemicals have a hormone-like action both in humans and in animals. DECD is developing screening programs using validated test systems to determine whether certain substances may have an effect in humans. In the present study. the establishment oj repeated-dose toxicity test method was tried. Flutamide. an anti-androgenic agent. was administered by gavage to Sprague-Dawley rats for 28 days at dose levels of 0. 0.5. 3 and 18 mg/kg body weight (10-15 rats/sex/group) to examine the effects on general findings. especially reproductive and endocrine parameters. Clinical signs. body weights, food consumption, and sexual cycle were checked and measured. For the gross and microscopic examinations. 10 rats/sex/group were sacrificed at the end of dosing period and the remaining animals of control and high dose groups (5 each) were sacrificed after 14 days recovery. Examinations for hematology and clinical chemistry were carried out at necropsy. There were no treatment-related changes in clinical signs. body weights, food consumption. gross necropsy. hematology and clinical chemistry at all doses of both sexes. The period and regularity of sexual cycle were not adversely affected at all doses by the test agent. At 18 mg/kg. both decreased weights of prostate, seminal vesicle and epididymis in males and increased weights of spleen and thymus in females were observed. In addition, decreased number of spermatids and sperms. increased serum testosterone concentration and increased incidence (100%) of interstitial cell hyperplasia were seen in males. At 18 mg/kg of the recovery group. decreased prostate weight. reduced sperm count and increased incidence (20%) of interstitial cell hyperplasia in males and increased thymus weight in females were observed. At 3 mg/kg. reduced sperm count was found. There were no adverse effects on parameters examined at 0.5 mg/kg of both sexes. The results suggested that the potential target organs of flutamide may be accessory sexual glands including testes for males and spleen and thymus for females. Taken together. this test method was found to be a useful screening test system for endocrine disrupting chemicals.