• Journal of Sasang Constitutional Medicine
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• v.22 no.2
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• pp.101-107
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• 2010

1. Objectives: The aim of this study is to investigate the acute toxicity and safety of Taeeumjowi-tang. 2. Methods: We investigated the acute toxicity for water-extracted Taeeumjowi-tang. 25 male and 25 female mice were observed for 14 days after one day oral administration of Taeeumjowi-tang at the respective doses of 0(control group), 2560, 3200, 4000 and 5000 mg/kg. 3. Results: We observed survival rates, general toxicity, change of body weight and autopsy. 4. Conclusions: The data confirmed that Taeeumjowi-tang is free from the toxicity and safety problems in oral route respectively. Compared with the control group, we could not find any toxic alteration in all treated groups(2560, 3200, 4000 and 5000 mg/kg). In conclusion, LD50 of Taeeumjowi-tang was over 5000 mg/kg and it is very safe to mice.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.89-89
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• 2001

Paclitaxel is currently administered i.v. as a slow infusion of a solution of the drug in an ethanol: cremophor EL: saline admixture. However, poor solubilization and toxicity are associated with this drug therapy. We have tried to develop a new surfactant for paclitaxel to improve efficacy and reduce toxicity of solubilizer. We performed the hemolysis test for chemicals which passed the paclitaxel-stabilizing test and 5 chemicals showing relatively low hemolytic effects were tested for a single dosing toxicity test. And then aceporol 330, which showed the most favorable result, was introduced to the repeated dosing toxicity tests in mouse and beagle dog. According to data based on body weight, mortality, dissection, homological test and biochemical test, Aceporol 330 exhibited much more reduced toxicity than cremophor EL.

• Journal of Sasang Constitutional Medicine
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• v.21 no.1
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• pp.247-253
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• 2009

1. Objectives This study was designed to andyze the acute toxicity and safety of Yeoldahanso-tang 2. Methods We investigated the acute toxicity for water-extracted Yeoldahanso-tang. 25 male and 25 female mice were observed for 14 days after one day oral administration of Yeoldahanso-tang at the respective doses of 0(control group), 2560, 3200, 4000 and 5000 mg/kg. 3. Results We observed survival rates, general toxicity, change of body weight and autopsy. 4. Conclusions The data confirmed that Yeoldahanso-tang is free from the toxicity and safety problems in oral route respectively. Compared with the control group, we could not find any toxic alteration in all treated groups(2560, 3200, 4000 and 5000 mg/kg). In conclusion, LD50 of Yeoldahanso-tang was over 5000 mg/kg and it is very safe to mice.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.161-172
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• 1994

This study was conducted to examine DA-3002, a biosynthetic human growth hormone, for its acute and subacute toxicities in mice and rats. The drug was administered subcutaneously and orally at a dose level of 1.0, 3.0, 8.9, 26.7 or 80.0 lU/kg once for single dose toxicity and given subcutaneously at a dose level of 0.34, 1.7 or 8.4 lU/kg daily for 13 weeks to investigate repeated dose toxicity. In the acute toxicity study, doses up to 80 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal changes which could be attributed to toxic effect of DA-3002. In the subacute toxicity study, the growth hormone was tolerated well in broth mice and rats. No drug related deaths occurred and all animals appeared to be normal throughout the dosing period. Increases in body weight gain, food utilisation and absolute organ weights were observed in the rats in the high dose group. Mild changes in the blood chemical parameters were also seen in the treated groups. Histopathologically, however, no abnormal changes were observed in any organ. The changes noted during the treatment periods presumably represent exaggerated pharmacological effects of the growth hormone, and no observed adverse effect level (NOAEL) was considered to be more than 8.4 lu/kg/day.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.442-448
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• 2006

To obtain the 50% lethal dose (LD50), approximated lethal dose (ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study like repeat dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male ICR mouse according to KFDA Guideline 1999-61 [KFDA, 1999] at a dosage level of 2,000, 1,000, 500, 250 and $125\;mg/kg/10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. After 2 or 3 days of dosing, 1 or 2 animals in 2,000 and 1,000 mg/kg-dosing groups were died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and they were recovered to normal within 4 days after dosing in case of survivors. A significant decrease of body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group from 1 days after dosing compared to those of vehicle control group. A significant decrease of body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. LD50 in this study was detected as 2,242.42 mg/kg. ALD in this study was detected as 1,000 mg/kg and the target organ was considered as the heart and kidney.

• Molecules and Cells
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• v.40 no.4
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• pp.280-290
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• 2017

Several lines of evidence suggest that endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Protein tyrosine phosphatase 1B (PTP1B) is known to regulate the ER stress signaling pathway, but its role in neuronal systems in terms of ER stress remains largely unknown. Here, we showed that rotenone-induced toxicity in human neuroblastoma cell lines and mouse primary cortical neurons was ameliorated by PTP1B inhibition. Moreover, the increase in the level of ER stress markers ($eIF2{\alpha}$ phosphorylation and PERK phosphorylation) induced by rotenone treatment was obviously suppressed by concomitant PTP1B inhibition. However, the rotenone-induced production of reactive oxygen species (ROS) was not affected by PTP1B inhibition, suggesting that the neuroprotective effect of the PTP1B inhibitor is not associated with ROS production. Moreover, we found that MG132-induced toxicity involving proteasome inhibition was also ameliorated by PTP1B inhibition in a human neuroblastoma cell line and mouse primary cortical neurons. Consistently, downregulation of the PTP1B homologue gene in Drosophila mitigated rotenone- and MG132-induced toxicity. Taken together, these findings indicate that PTP1B inhibition may represent a novel therapeutic approach for ER stress-mediated neurodegenerative diseases.

• The Journal of Internal Korean Medicine
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• v.34 no.1
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• pp.46-58
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• 2013

Objectives : The object of this study was to obtain acute information (single oral dose toxicity) of Scutellariae Radix Aqueous Extracts (SR; yield = 27.20%) which traditionally have been used in Korean medicine for treating various diseases including inflammatory diseases. Methods : In order to observe the 50% lethal dose ($LD_{50}$), approximate lethal dosage (ALD) and target organs, SR Aqueous Extracts were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight.) according to the recommendation of KFDA Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after single oral treatment of SR according to KFDA Guidelines with organ weights and histopathological observations of 14 types of principle organs. Results : After single oral treatment of SR, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents, on the body and organ weights, clinical signs, gross and histopathological observations, except for some accidental findings. Conclusions : The results obtained in this study suggest that the $LD_{50}$ and ALD of SR in both female and male mice after single oral treatment be considered as over 2,000 mg/kg because no mortalities were detected up to 2,000 mg/kg that was the highest dose recommended by KFDA and OECD, and can be safely used in clinics.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.7
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• pp.986-990
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• 2003

The living Glass puffers, Takifugu niphobles (Bogseom as Korean name), 10 specimens, were purchased at Tongyeong traditional fisheries market every month from November, 2001 to October, 2002, and tested anatomical distribution of the toxicity such as muscle, skin, intestine, liver and ovary by mouse bioassay method. Significant seasonal variations of the toxicity were not shown in muscle, skin, intestine and liver except having lower toxicity in spawning season (May and June) than non-spawning seasons. 92 specimens (76.7%) out of 120 ones were non toxic (below 10 MU/g) for the edible and 28 ones (23.3%) were weakly toxic (10 MU/g∼l00 MU/g) for the non-edible in muscle ranged between 0 MU/g and 46.4 MU/g. All of those toxicity were shown over 10 MU/g in skin for the non-edible in skin ranged from 10.0 MU/g to 674.4 MU/g. Toxicity range in intestine and liver was varied between non-toxic and strongly toxic (over 1,000 MU/g) for individual specimens. Toxicity range of the ovary found only in May (7 specimens) and June (1 specimens) was 84.2 MU/g to 2,191.3 MU/g.

• Applied Microscopy
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• v.18 no.2
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• pp.187-204
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• 1988

The present experiment was performed to investigate the acute and subacute effect of lead acetate on ultrastructural and biochemical changes in mouse diencephalon. In acute case, mouse were peritoneally injected with lead acetate at a dose of 0.26 mmole/kg body weight, and after treatment, mouse were sacrificed at time intervals of 12, 24, 48, and 96 hours. In subacute case, mouse were injected at doses of 0.07 mmoie/kg B. W. and 0.13 mmole/kg B.W. once at two days, and after treatment, mouse wee sacrificed at 1 week, 2 weeks, and 3 weeks. It was observed that after acute treatment, changes composed of increased monoamine oxidase activity, $Na^{+}-K^{+}$ ATPase activity, decreased $Mg^{2+}$-APTase activity, wrinkled myelin, swollen Golgi apparatus and more dense synaptic vesicle in nerve terminal. After subacute treatment, decreased monoamine oxidase activity, increased $Mg^{2+}$-ATPase, $Na^{+}-K^{+}$ ATPase, lose of myelin, uneven mitochondrial distribution, synaptic vesicular density and edema, but at a higher dose the effect was more severe. Therefore, lead acetate caused abnormal change of diencephalon, and at a subacute, it appears metal accumulative toxicity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.5
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• pp.612-617
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• 2008

Tetrodotoxin (TTX) analogues were first determined from the liver extracts of puffer fish, Takifugu niphobles, by LC/MS with Hydrophilic Interaction Liquid Chromatography (HILIC). In total, 7 TTX analogues were detected within 20 minutes as follows; 5,6,11-trideoxyTTX (34.0%, 1,029.6 nmol/g), 6,11-dideoxyTTX (29.3%, 887.6 nmol/g), TTX (22.1%, 667.8 nmol/g), 4,9-anhydro-TTX (11.2%, 339.3 nmol/g), 11-deoxyTTX＋5-deoxyTTX (2.6%, 78.6 nmol/g), and 4-epiTTX (0.8%, 23.6 nmol/g). Mouse toxicity of diluted liver extracts showed the highest toxicity at pH 3 (8.7 MU/mL) and decreased, as increasing pH, to 1.4 MU/mL at pH 10. At acidic (pH 5) and neutral conditions (pH 7), mouse toxicity of liver extracts (79 MU/mL) decreased slowly, as increasing temperature from $80^{\circ}C$ to $115^{\circ}C$, and time until 1 hour; in contrast, at the akaline condition (pH 9), the toxicity decreased rapidly to the more than half within 10 minutes. Individual toxicity of the fillet of T. niphobles were between $43.2{\sim}106.7$ MU, and $64{\sim}78%$ of its toxicity was eluted to soup when boiled with 3 volumes of water during 10 minutes.