• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.11a
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• pp.11-15
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• 2007

Metabolomics is an emerging technology which makes it possible to evaluate change of biological system in response to the physiological, environmental alterations. It has advantages in the simplicity and sensitivity to analyze metabolites since the researcher can use cutting edge instrument, such as mass spectrometry and simple sample preparation method compared to genomics or proteomics. Nowadays this technology has been tried in pharmaceutical area to investigate toxicity and efficacy of drug candidates and drugs in preclinical test. The metabolomic applications on the pharmaceutics for early prediction on toxicity and efficacy are described in this presentation. The multivariate analysis to get metabolic fingerprinting and its relations with the physiological changes are investigated with several drugs. Feasibility of metabolomic application for pharmaceutical area would be suggested from those researches.

• KSBB Journal
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• v.9 no.3
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• pp.266-271
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• 1994

Lipsome system composed of egg phosphatidylcholine was employed to reduce the membrane toxicity of Amphotericin B(Amp. B). Liposomal Amp. B, which showed a free drug equivalent antibiotic effect on fungi, displayed a remarkable reduction of toxicity of the drug against the membrane of red blood cell than that of fungizone which has been used in clinical treatment, and it shows conspicuously lowered toxicity on red blood cells. However liposomal Amp. B which contains cholesterol as a component of liposome lowered the antibiotic effect and toxicity than that phosphatidylcholine liposome. This due to the affinity between Amp. B and cholesterol. In addition to this, ${\beta}$-glucuronidase from snail juice crude enzyme reveals synergistic effect on liposomal Amp. B and free Amp. B. We also obtained positively raised antibiotic effect, when enzyme which is coupled with palmitic acid using NHSP inserted into liposome bilayer From these results, we suppose that the use of liposomal system in the case of Amp. B shows increasing antibiotic effect and dramatically lowered toxicity, thus, we think that we can solve the problem of Amp. B toxicity, which cause hesitate of clinical use.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.11a
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• pp.55-56
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• 2007

• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.165-171
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• 2007

Mitomycin C (MMC), an antitumor antibiotic isolated from Streptomyces caespitosus, is used in chemotherapy of gastric, bladder and colorectal cancer. MMC is activated in vivo to alkylate and crosslink DNA, via G-G interstrand bonds, thereby inhibiting DNA synthesis and transcription. This study investigates gene expression changes in response to MMC treatment in order to elucidate the mechanisms of MMC-induced toxicity. MMC was admistered with single dose (0.32 and 1.6 ${\mu}M$) to TK6 cells. Applied Biosystem's DNA chips were used for identifying the gene expression profile by MMC-induced toxicity. We identified up- or down-regulated 90 genes including cyclin M2, cyclin-dependent kinase inhibitor 1A (p21, cip1), programmed cell death 1, tumor necrosis factor (ligand) superfamily, member 9, et al. The regulated genes by MMC associated with the biological pathways apoptosis signaling pathway. Further characterization of these candidate markers related to the toxicity will be useful to understand the detailed mechanism of action of MMC.

• Natural Product Sciences
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• v.21 no.1
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• pp.34-41
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• 2015

The objective of this study is to characterize a toxicity of Epimedii Herba (EH) in F344 rats and to find a dose levels for the 13 weeks toxicity study. EH is well known as medicinal herb in many Asian countries for traditional medicines of antibacterial and antiviral effects, estrogenic and antiestrogenic effects, and for treatment of osteoporosis, hypotensives, fatigue, kidney disorders, and related complications. However, the indispensable and basic information of toxicological evaluation of EH extract is insufficient to support its safe use. Therefore, we conducted toxicological evaluation of this drug in compliance with OECD and MFDS guideline in this study. The extract of EH was administered orally to F344 rats at dose levels of 0, 500, 1000, 2000, 3500, and 5000 mg/kg/day for 2 weeks. Each group was composed of 5 male and female rats. In this study, there were no treatment of EH-related adverse changes in clinical observations, mortality, body weights, food consumption, urinalysis, gross finding at necropsy, and organ weight examination. Total red blood cell count, hematocrit, mean corpuscular hemoglobin concentration, total cholesterol, and phospholipid were decreased in males and females at 5000 mg/kg/day compared to the control animals. Mean corpuscular volume and reticulocyte counts were increased in males and females at 5000 mg/kg/day compared to control animals. Therefore, we recommend that dose level of 5000 mg/kg/day is a highest treatment group in 13-week EH extract exposure study for further toxicity assessment.

• Toxicological Research
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• v.27 no.2
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• pp.61-70
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• 2011

Brominated flame retardants (BFRs) are present in many consumer products ranging from fabrics to plastics and electronics. Wide use of flame retardants can pose an environmental hazard, which makes it important to determine the mechanism of their toxicity. In the present study, dose-dependent toxicity of tetrabromobisphenol A (TBBPA), a flame retardant, was examined in male prepubertal rats (postnatal day 18) treated orally with TBBPA at 0, 125, 250 or 500 mg/kg for 30 days. There were no differences in body weight gain between the control and TBBPA-treated groups. However, absolute and relative liver weights were significantly increased in high dose of TBBPA-treated groups. TBBPA treatment led to significant induction of CYP2B1 and constitutive androstane receptor (CAR) expression in the liver. In addition, serum thyroxin (T4) concentration was significantly reduced in the TBBPA treated group. These results indicate that repeated exposure to TBBPA induces drug-metabolising enzymes in rats through the CAR signaling pathway. In particular, TBBPA efficiently produced reactive oxygen species (ROS) through CYP2B1 induction in rats. We measured 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, in the kidney, liver and testes of rats following TBBPA treatment. As expected, TBBPA strongly induced the production of 8-OHdG in the testis and kidney. These observations suggest that TBBPA-induced target organ toxicity may be due to ROS produced by metabolism of TBBPA in Sprague-Dawley rats.

• Natural Product Sciences
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• v.14 no.2
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• pp.122-126
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• 2008

Chronic oral toxicity studies (90 days) on aqueous and methanol extracts of the whole plant of Peristrophe paniculata (Forssk) Brummitt were carried out in Wistar rats. The dosage was 200 mg/kg/day, p.o. for both the extracts. All external morphological and biochemical changes, in addition to body weight and vital organ weights were recorded. During this investigation, no significant mortality was observed. The results showed that both the extracts were devoid of any toxicity at the dose level studied as compared to the control group.

• Electronics and Telecommunications Trends
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• v.38 no.1
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• pp.46-54
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• 2023

The announcement of the US Environmental Protection Agency that it will stop conducting or funding experimental studies on mammals by 2035 should prioritize ongoing efforts to develop and use alternative toxicity screening methods to animal testing. Toxicity screening is likely to be further developed considering the combination of human-induced pluripotent-stem-cell-derived organ-on-a-chip and multielectrode array (MEA) technologies. We briefly review the current status of MEA technology and MEA-based neuropharmacological drug screening using various cellular model systems. Highlighting the coronavirus disease pandemic, we shortly comment on the importance of early prediction of toxicity by applying artificial intelligence to the development of rapid screening methods.

• 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.

• 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.