• Toxicological Research
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• v.28 no.1
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• pp.11-18
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• 2012

The aim of this study was to evaluate the single oral dose toxicity of Bupleuri Radix (BR) aqueous extracts, it has been traditionally used as anti-inflammatory agent, in male and female mice. BR extracts (yield = 16.52%) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (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 14 principal organs were examined. As the results, no BR extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs were detected up to 2,000 mg/kg in both female and male mice, except for soft feces and related body weight decrease detected in male mice treated with 2,000 mg/kg. Therefore, $LD_{50}$ (50% lethal dose) and approximate LD of BR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg, respectively. Although it was also observed that the possibilities of digestive disorders, like soft feces when administered over 2,000 mg/kg of BR extracts in the present study, these possibilities of digestive disorders can be disregard in clinical use because they are transient in the highest dosages male only.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2002.10a
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• pp.172-172
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• 2002

Previously, we reported a novel polymeric micellar solubilizer, Aceporol 330, that showed relatively low toxic effects when it was compared with that of Cremophor EL which is currently being used for paclitaxel. In this study, we have developed a new micellar solubilizer, Aceporol 460, that has 3-4 times higher loding capacity for paclitaxel than Aceporol 330. The single-dose and the repeated-dose toxicity of Aceporol 460 were evaluated in ICR mice. For single dose toxicity test, male and female mice were randomly assigned to one of five study groups to receive, and injected intravenously with dosages of 0, 3, 4mL Cremophor EL/kgbody weight, and 3, 4mL Aceporol 460/kg body weight, respectively. In both male and female mice, LD50 for Aceporol 460 can not he determined even at the maximal administrable dosage, 4mL/kg due to the high viscosity of chemical and there was no significant change in body weight, hematological and serum biochemical analysis, organ weight, and histopathological examination compared with that of Cremophor EL. For the repeated dose toxicity test, male and female mice were given the dosage of 0, 1.6mL Cremophor EL/kgbody weight/day, and 1.6mL Aceporol 460/kg body weight/day for 2 weeks. Results of repeated dose toxicity tests for 2 weeks suggested that Aceporol 460 treated group show no significant toxicological findings with body weight, hematological and serum biochemical analysis, organ weight, urinalysis, and ophthalmoscopic and histopathological examination compared with that of Cremophor EL. These results indicate that Aceporol 460 have higher paclitaxeL-loading capacity than Aceporol 330 and less toxic effects than Cremophor EL in male and female mice.

• Toxicological Research
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• v.8 no.2
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• pp.205-216
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• 1992

cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R), an antitumor platinum complex, was selected for clinical evaluation on the basis of its experimental antitumor and toxicologic profiles in preclinical studies. These studies were performed to obtain information on its toxic signs, orgnas which are mainly affected, and to estimate its lethality in mice and rats given SKI 2053R through two routes of administration. In male and female rats given a single intragastrical dose of SKI 2053R, we estimated that $LD_{50}$ values were over 3.00g/kg, respectively. In male and female mice given a signle intragastrical dose of SKI 2053R, we estimated that $LD_{50}$ values were 2.44g/kg and 1.59g/kg, respectively, In a single intraperitoneal dose of SKI 2053R, we determined that $LD_{50}$ values of male and female rats were 227mg/kg and 182mg/kg, and those of male and female mice were 198mg/kg and 207mg/kg, respectively. In gross and histopathological examinations on dead animals, we found that kidney and liver were mainly affected.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.769-773
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• 1998

Brazilin was examined for its effects on the induction of immunological tolerance. Brazilin was administered to C57BL/6 female mice for 2 consecutive days before the immunization with high dose SRBC (109 cells) which can produce immunological tolerance. Delayed type hypersensitivity, IgM plaque forming cells, ConA induced IL-2 production and mitogen- or antigen-induced proliferation of lymphocytes were measured as evaluation parameters. Administration of brazilin prior to immunization could keep the DTH and IL-2 production almost optimaly immunized levels. Brazilin also inhibited the elevation of non-specific suppressor cell activity. ConA induced proliferation of splenocytes in high dose SRBC immunized mice was significantly decreased by pretreatment of brazilin. And this might be one of the reason for augmentation of DTH by brazilin. However, IgM plaque forming cells were not affected by the treatment of brazilin. These results indicate that brazilin prevents the induction of mmunological tolerance caused by high dose SRBC by suppressing the elevation of suppressor cell activity and by inhibiting the decrease in IL-2 production in C57BL/6 female mice.

• The Journal of Internal Korean Medicine
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• v.32 no.4
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• pp.599-609
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• 2011

Objectives : The aim of this study was to evaluate the single oral dose toxicity and safety of Bojungikgi-tang (Buzhongyiqi-tang) and fermented Bojungikgi-tang (Buzhongyiqi-tang) extracts in male and female ICR mice. Methods : In the single oral dose toxicity study, non-fermented and fermented Bojungikgi-tang (Buzhongyiqi-tang) were administered to male and female ICR mice as an oral dose of 1250, 2500 and 5000 mg/kg. Changes of body weights, general behaviors, adverse effects and mortality were determined throughout the experimental period. Hematological parameters, serum chemistry, organ weights and necropsy findings were evaluated at the end of the experiment. Results : There was no mortality or sign of toxicity in the single oral dose toxicity study. There were also no significant differences in body weights, organ weights, and hematological parameters, serum chemistry values between treatment and control groups. Conclusions : The results obtained in this study suggest that the 50% lethal dose of fermented Bojungikgi-tang (Buzhongyiqi -tang) in both female and male mice can be considered as well over 5,000 mg/kg, so these medicines can be safe in clinics.

• Biomolecules & Therapeutics
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• v.15 no.2
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• pp.127-132
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• 2007

The object of this study was to evaluate the acute toxicity of lyophilized water extract of Radix Araliae Cordatae (RA) in male and female mice. The extract was administered to female and male ICR mice as an oral dose of 2000 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, changes in the body weight and gross findings except for increases of hypertrophy of lymph nodes in male RA extracts-dosing group. In addition, no RA extracts-treatment related abnormal changes in the organ weight and histopathology of principle organs except for some sporadic accidental findings. The results obtained in this study suggest that the RA extracts does not cause any toxicological signs. The LD$_{50}$ and approximate LD of RA extracts in both female and male mice were considered as over 2000 mg/kg.

• Journal of Korean Academy of Nursing
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• v.31 no.2
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• pp.268-278
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• 2001

Many women in the world have suffered from anemia produced by menstruation, pregnancy and delivery. In the theory of oriental medicine, a sour taste is believed to have a tonic effect on the blood. Thus this paper is to investigate the effect of sour tastes on the improvement in anemia-induced female mice, using citric acid and Fructus schizandrae(五味子). The method used in this experiment was the change of RBC, WBC, Hemoglobin, Hematocrit, Fe, and TIBC in the blood of female mice who were fed citric acid and Fructus schizandrae(五味子). The results obtained were as follows ; 1. Compared with the control group (anemia- induced group without treatment), the mean number of RBC in the blood of mice was significantly increased only in evaluating the change of sample group fed Fructus schizandrae (五味子) 500mg/kg. 2. Compared with the control group (anemia- induced group without treatment), the mean number of WBC in the blood of mice was not significantly larger in both sample groups fed citric acid and Fructus schizandrae(五味子). 3. Compared with the control group (anemia- induced group without treatment), the mean number of Hemoglobin in the blood of mice was significantly larger only in evaluating the change of the sample group fed Fructus schizandrae(五味子). 4. Compared with the control group (anemia- induced group without treatment), the mean percentage of Hematocrit in blood of mice was significantly increased only in evaluating the change of sample group fed Fructus schizandrae(五味子) 500mg/kg and sample group fed Fructus schizandrae(五味子) 250mg/kg for 3days. 5. Compared with control group (anemia- induced group without treatment), the mean volume of Fe in serum of mice was significantly increased only in evaluating the change of sample group fed Fructus schizandrae(五味子) 500mg/kg. 6. Compared with control group (anemia- induced group without treatment), the mean TIBC in serum of mice was significantly increased only in evaluating the change of sample group fed Fructus schizandrae(五味子) 500mg/kg and sample group fed Fructus schizandrae(五味子) 250mg/kg for 7days. According to these results, a sour taste is presumed to have a general tonic effect on anemia, but more study must be taken on the effects of citric acid in improving female anemia.

• Development and Reproduction
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• v.18 no.4
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• pp.301-309
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• 2014

Nesfatin-1, an anorexic nucleobindin-2 (NUCB2)-derived hypothalamic peptide, controls appetite and energy metabolism. Recent studies show that nesfatin-1/NUCB2 is expressed not only in the brain but also in gastric and adipose tissues. Thus, we investigated the distributions of nesfatin-1/NUCB2 in various tissues of male and female mice by real-time PCR, western blotting, and immunohistochemical staining. Real-time PCR analyses showed that NUCB2 mRNA was predominantly expressed in the pituitary and at lower levels in the hypothalamus, spleen, thymus, heart, liver, and muscle of both male and female mice. Expression was much higher in reproductive organs, such as the testis, epididymis, ovary, and uterus, than in the hypothalamus. Western blot analysis of the nesfatin-1 protein level showed similar results to the real-time PCR analyses in both male and female mice. These results suggest that nesfatin-1/NUCB2 have widespread physiological effects in endocrine and non-endocrine organs. In addition, immunohistochemical staining revealed that nesfatin-1 was localized in interstitial cells, including Leydig cells and in the columnar epithelium of the epididymis. Nesfatin-1 was also expressed in theca cells and interstitial cells in the ovary and in epithelial cells of the endometrium and uterine glands in the uterus. These results suggest that nesfatin-1 is a novel potent regulator of steroidogenesis and gonadal function in male and female reproductive organs. Further studies are required to elucidate the functions of nesfatin-1 in various organs of male and female mice.

• Journal of Applied Biological Chemistry
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• v.58 no.1
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• pp.75-79
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• 2015

Extracted mushroom water showed an ability to suppress the accumulation of body fat in female mice after feeding 5 weeks with high fat diet. Particularly, in parametrial and mesenteric adipose, it significantly reduced 44 and 47% of weight, respectively. In non-obese mice, maturated NK cell ($CD11b^{hi}CD27^{lo}$) population were increased ($70.9{\pm}3.8%$) in mushroom water fed mice compared to control ($61.4{\pm}4.3%$) and NK cell population were augmented in mushroom fed mice compared to control.

• Toxicological Research
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• v.22 no.2
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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.