• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.846-853
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• 2004

This study was carried out for establishment of toxicological monitoring system in oriental medicinal plants. Hence on our research, we used Banha(Pinellia ternata) and Kangbanha, Bubbanha, Jaebanha, Geokbanha by distinguished processing methods. These are frequently used in Bangyakhabpeon, which is one of the most well-known clinical book in oriental medicine. As we reviewed the reported documents, we judge homogentisic acid(HA) and 3,4-dihydroxybenzaldehyde(3,4-DBA) as poisonous substance and to verify its existence, we established analysis condition of HPLC by gaining sequential fraction extracts and studied the degree of its virulence to provide basic information on the guidelines of using this medicine. Optimum condition of HPLC was H₂O : MeOH : CH₃COOH (57:35:8) in HA and 3,4-DBA analysis. HA content of raw Banha was 11.03mg/100g and HA contents of its processed product were decreased. Exceptionally, Jaebanha was increased in 175.97% than raw Banha. 3,4-DBA content of raw Banha was 2.93mg/100g and 3,4-DBA contents of its processed product were decreased. These results will be applies in intake guideline establishment, quality control and stability evaluation of oriental medicinal plants.

• Herbal Formula Science
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• v.20 no.1
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• pp.13-24
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• 2012

Objectives : Yukmijihwang-tang(Wan), a well-known formula for invigorating yin-particular kidney yin, was first recorded in "Xiao er Yao Zheng Zhi Jue", consisting of Radix Rehmanniae Preparata, Fructus Macrocarpii, Rhizoma Dioscoreae Oppositae, Poria, Rhizoma Alismatis and Cortex Moutan Radicis with dose proportion of 8:4:4:3:3:3. Although clinical trials have been lacking, various pharmacological actions for Yukmijihwang-tang has been identified newly using animal models. In addition, it was reported that Yukmijihwang-tang increases structural chromosome aberrations significantly in Chinese hamster lung cells. In this article, it is purposed that new studies for pharmacology and toxicology of Yukmijihwang-tang are reviewed. Insight into new studies of Yukmijihwang-tang at the cellular and animal levels will enhance our understanding of Yukmijihwang-tang against various diseases will provide new tools to diagnose and treat patients. Methods : Recent researches for Yukmijihwang-tang were reviewed and summarized in terms of pharmacological action and toxicity. All sources for review were based on recent studies loaded on data base of web sites such as Science Direct and National Center for Biotechnology Information. Results and Conclusions : Recently, reports showed that YMJ had antiaging effects, antioxidant and free radical scavenging activities, anti-renal hypertension and prevented tumors, and diabetes mellitus. However, there is little information on its safety except general toxicity, acute and sub-chronic oral toxicity, or genotoxicity. In addition, clinical trial for Yukmijihwang-tang was limited even though Yukmijihwang-tang has been used extensively in Korean traditional medicine. Thus, further studies are necessary to focus on safety evaluation and clinical trial for Yukmijihwang-tang.

• Journal of Environmental Health Sciences
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• v.46 no.4
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• pp.470-479
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• 2020

Objectives: The Coronavirus Disease 2019 (COVID-19) pandemic has caused the death of 740,000 people around the world as of August 12, 2020. Foot-and-Mouth Disease, Avian Influenza, and African Swine Fever are serious livestock diseases. Government agencies in Korea have provided ingredient information and usage instructions for disinfectants used to counter those infectious diseases. The purpose of this study was to provide information on the chemical ingredients in disinfectant products used against COVID-19 and certain livestock diseases. Methods: We collected information from the Korean government. The Central Disaster Management Headquarters and Central Disease Control Headquarters provided information on disinfectant products used against COVID-19. The Animal and Plant Quarantine Agency of Korea provided information on efficacy-certified disinfectant products for use against selected livestock diseases. Health hazard and environmental hazard information on the ingredients in the disinfectants was collected from the Korea Occupational Safety & Health Agency's Material Safety Data Sheets, and toxicity value information was collected from United States Environmental Protection Agency's CompTox Chemicals Dashboard. Results: There were 76 COVID-19 disinfectant products in use, and the most common ingredients were benzalkonium chloride (51%), alkylbenzyl dimethyl ammonium (30%), and ethanol (3%). There were 216 livestock disease disinfectant products comprised of 89 acidic, 88 oxidic, 30 aldehydic, three alkaline, and six other products. Among the 49 active ingredients used in the disinfectants that were investigated, health and environmental hazard information was provided for many of them, but only 20 chemicals had official toxicological information. Conclusion: Since the disinfectants included numerous chemicals, an understanding of their chemical characteristics could be critical to prevent unintended human or environmental exposure.

• The Korea Journal of Herbology
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• v.20 no.4
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• pp.83-94
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• 2005

Objectives : The present study attempted to reveal the effects of Morindae Radix extracts on the sciatic nerve neurectomized osteoporotic ddy mice model. Methods : Thickness of hind limbs and their differences, absolute and relative tibia weight and thickness, bone failure load, bone mineral density (BMD), histomorphometrical index, serum osteocalcin level, tibia calcium and phosphorus contents were monitored. Results : In sciatic neurectomized mice, thickness of hind limb, absolute and relative weights, thickness, failure loads, BMD of tibia, trabecular bone volume (TBV), thickness of trabecular bone and cortical bone thickness, length were significantly decreased. However, these changes of those dose-dependently reduced in MR extract-dosing group. Conclusions : it is considered that MR extracts have some favorable effect to prevent, the osteoporosis induced by sciatic neurectomy. However, the exact mechanism and the possibility of MR extract were remains unknown. In addition, the potential toxicity of these MR extracts were also unknown. So the further studies were needed about toxicological and pharmacological aspects.

• Toxicological Research
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• v.34 no.1
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• pp.55-63
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• 2018

As a part of general toxicity studies of Enterococcus Faecalis 2001 (EF 2001) prepared using heat-treatment bacillus mort body EF 2001 in mice, this study examined the toxicity of EF 2001 in single and repeated administrations following the previous report in order to apply this product to preventive medicine. The safety of oral ingestion of EF 2001 was examined in 6-week-old male and female ICR mice with 1,000 mg/kg, 3,000 mg/kg and 5,000 mg/kg body weight/day administrated by gavage of the maximum acceptable dose of EF 2001. The study was conducted using distilled water as a control following the methods for general toxicity studies described in the "Guidelines for Non-clinical Studies of Pharmaceutical Products 2002". As a control, 1) observation of general conditions, 2) measurement of body weight, 3) determination of food consumption, 4) determination of water consumption, 5) blood test and urinalysis and 6) pathological examination were performed for the administration of EF 2001. Mice received EF 2001 for 13 weeks and results were compared with those of the control group that received distilled water. The results of the above examinations revealed no significant differences between control and EF 2001 groups for both males and females. Thus, no notable toxicity was confirmed with single and repeated oral administrations of EF 2001. Oral administration in the above doses did not result in abnormal symptoms or death during the observation period. No abnormalities in blood cell count or organ weights were seen. Without any evidence of toxicity to cells and organs, EF 2001 is speculated to not adversely affect living organisms. The 50% lethal dose of EF 2001 with oral administration in mice is estimated to be greater than 5,000 mg/kg body weight/day for both male and female mice. Therefore, $LD_{50}$ value for animals was 5,000 mg/kg or more.

• Toxicological Research
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• v.3 no.1
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• pp.15-26
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• 1987

The mutagenicity of pranoprofen, a new antiinflammatory agent primarily used in Japan, was evaluated by employing several different methods such as the Ames test, micronucleus test, and the sister chromatid exchange test. For the Ames test, various doses of pranoprofen (5 and 1 mg, 100, 10, and 1 ${\mu}$g per plate) were applied, with or without the mammalian liver S-9 fraction, to the S. typhimurium LT2. For the micronucleus test, 24 hours after administering the various doses of pranoprofen (200, 100, and 50 mg/kg) to male mice by aral intubation, the femura of each group were isolated and the bone marrow samples were prepared. The micronucleated red cells and the ratio of the polychromatic versus the normochroomatic cells were counted. For the sister chromatid exchange test, the maximal non-cytotoxic concentrations (10 to 0.1 mM pranoprofen) were applied to the culture media of the Chinese Hamster Ovary (CHO) cells for 24 hrs. The numbers of revertant colonies did not increase with the increasing doses of pranoprofen when teseted with various strains of S. typhimurium. In the micronucleus test employing mice, the pranoprofen was identkfied to be a non-clastogen and a non-spindle poison. In the sister chromatid exchange test employing the cultured CHO cells, the pranoprofen did not increase the incidences of chromosomal abnormality. Based on these results, pranoprofen was found to have no mutagenic activity.

• Journal of Korean Neurosurgical Society
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• v.38 no.5
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• pp.366-374
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• 2005

Objective : Nitric oxide[NO] is implicated in a wide range of biological processes in tumors and is produced in glioma. To investigate the role of NO and its interaction with the tumoricidal effects of anticancer drugs, we study the antitumor activities of NO donors, with or without anticancer drugs, in human glioma cell lines. Methods : U87MG and U373MG cells were treated with the NO donors sodium nitroprusside[SNP] and S-nitroso-N-acetylpenicillamine[SNAP], alone or in combination with the anticancer drugs 1,3-bis[2-chloroethyl]-1-nitrosourea[BCNU] and cisplatin. Cell viability, cell proliferation, DNA fragmentation, nitrite level, and the expression of Bcl-2 and Bax were determined. Results : NO was markedly increased after treatment with SNP or SNAP; however, the addition of the anticancer drugs did not significantly affect NO production NO donors or anticancer drugs reduced glioma cell viability and, in combination, acted synergistically to further decrease cell viability in a dose- and time-dependent manner. Cell proliferation was inhibited and apoptosis were enhanced by combined treatment. Bax expression was increased by combined treatment, whereas Bcl-2 expression was reduced. The antitumor cytotoxicity of NO donors and anticancer drugs differed according to cell type. Conclusion : BCNU or cisplatin can inhibit cell viability and proliferation of glioma cells and can induce apoptosis. These effects are further enhanced by the addition of a NO donor which modulates the antitumor cytotoxicity of chemotherapy depending on cell type. Further biological, chemical, and toxicological studies of NO are required to clarify its mechanism of action in glioma.

• The Journal of Internal Korean Medicine
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• v.31 no.3
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• pp.539-553
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• 2010

Objectives : The object of this study was to obtain accurate information (single oral dose toxicity) of Lonicerae Flos (LF; Dried flower bud parts of Lonicera japonica Thunb (Caprifoliaceae)), which has traditionally been used in Korean medicine for treating various inflammatory diseases. Methods : In order to observe the 50% lethal dose (LD 50), approximate lethal dosage (ALD) and target organs, test articles 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.). The mortality and changes on body weight, clinical signs and gross observation were monitored for 14 days after single oral treatment of LF aqueous extracts with organ weights and histopathological observations of 12 types of principle organs. Results : 1. After single oral treatment of LF aqueous extracts, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents at body and organ weights, clinical signs, gross and histopathological observations. 2. Slight diarrhea was detected in most mice treated with 2,000 mg/kg of LF aqueous extracts and male mice of LF aqueous extracts 1,000 mg/kg within 2 days after end of treatment, respectively. Conclusion : The results obtained in this study suggest that the LD 50 and ALD of LF aqueous extracts in both female and male mice after single oral treatment were considered as over 2,000 mg/kg because no mortalities were detected up to 2000 mg/kg, the highest dose recommended by KFDA and OECD. However, we also observed the possibility of digestive disorders like diarrhea when over 1,000 mg/kg of LF aqueous extracts were administered in the present study.

• Journal of Society of Preventive Korean Medicine
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• v.12 no.1
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• pp.89-102
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• 2008

Purpose : The experiments was undertaken to evaluate the effects of herbal medicine, Ojeoksan, in pregnant rats Methods : Female Sprague-Dawley rats were orally administered with the Ojeoksan at dose of 5mg/kg/day for 20 days. Pregnant rats were sacrificed at 20th day of gestation, and observed internal and reproductive organs. Approximately live fetuses in the 20th day of gestation were randomly selected and fixed in 95% ethanol. Results : Maternal body weight of Ojeoksan treated group has a tendency to increase compared to that of control group. There were no significant difference in internal and reproductive organs. There were no significant changes between two groups in blood chemistry and hematological values. There were no significant changes in number of corpus luteum, implantation, live fetuses and sex ratio. But Ojeoksan administered group showed higher delivery rate, early resorption rate than the control group. Also Ojeoksan administered group showed higher implantation rate, late resorption rate than the control group. Conclusion : From these results, it can be concluded that Ojeoksan showed no toxicity effects on maternal body weight and number of live fetuses. There were no significant changes in organ weight, hematological data, reproductive organs. We need more precise study to investigate the mechanism of early or late resoption by the herbal medicines such as Ojeoksan.

• Toxicological Research
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• v.17
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• pp.127-133
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• 2001

Together with cytochrome P450 (CYP), flavin-containing monooxygenase (FMO) present in liver microsomes oxidizes various endogenous and exogenous chemicals. In an effort to determine the human FMO activity, we have developed two non-invasive urine analysis methods using caffeine (CA) and ranitidine (RA) as the probe compounds. As the production of theobromine (TB) and ranitidine N-oxide (RANO) from CA and RA is catalyzed primarily by the hepatic FMO, we have assigned the urinary molar ratios of TB/CA and RA/RANO as the in vivo FMO activity. In 200 age-matched Korean volunteers, the obtained TB/CA ratio ranged from 0.4 to 15.2 (38-fold difference) and the RA/RANO ratio from 5.7 to 27.2 (4.8-fold). The FMO activity of 20's, determined by caffeine metabolism, was the highest (2.5$\pm$l.9) and those of 30's, 40's, 50's, 60's and 70's were 40%, 50%, 24%, 39% and 36% of the 20's, respectively. Intake of grapefruit juice, known to contain flavonoids, inhibited the in vivo FMO (TB/CA) activity by 79%. Addition of the flavonoids like naringin, quercitrin and kaempferol, present in grapefruit juice, to the in vitro microso-mal FMO assay, thiobenzamide S-oxidation, produced 75%, 70% and 60% inhibition, respectively. Obtained Ki values of quercitrin, kaempferol and naringin on the in vitro FMO activity were 6.2, 12.0 and 13.9 $\mu\textrm{M}$, respectively. This suggested that the dose of drug should need to be adjusted to suit the individual FMO activities when the drugs metabolized by FMO are given to patients. As the intake of grapefruit juice has been identified to inhibit the FMO as well as CYP3A4 and lA2 activities, patients taking drugs metabolized by these enzymes should not drink grapefruit juice as the carrier.