• YAKHAK HOEJI
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• v.57 no.4
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• pp.258-264
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• 2013

Herbal medicine has been traditionally used in Asian countries for a long time. Many pharmacological effects are identified in the herbs and these herbs are believed to be safe for human. However, the safety or adverse effect of some traditional herbal medicines has not been established. We have chosen Cyperi rhizoma based on the Korea Herbal Pharmacopoeia and which have been widely used for an anti-inflammatory effect in Korea. The object of the study was to evaluate safety of Cyperi rhizoma in rats. The aqueous extract of Cyperi rhizoma was prepared according to the standard hot water extraction method of the Korea Pharmacopoeia. In the sub-chronic study, the aqueous extract of Cyperi rhizoma was orally administered once daily as 0, 125, 250, 500, 1000 and 2000 mg/kg/day to male and female F344 rats for 13 weeks. There were no treatment related abnormalities in mortality, clinical signs, food consumption, ophthalmologic examination, hematology, serum chemistry, urinalysis, gross observation, organ weight and histopathologic examination. In conclusion, The NOAEL (No Observed Adverse Effect Level) for Cyperi rhizoma aqueous extract was determined as more than 2000 mg/kg/day in the present experimental condition.

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.307-312
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• 2013

Quetiapine is an atypical or second-generation antipsychotic agent and has been a subject of a series of case report and suggested to have the potential for misuse or abuse. However, it is not a controlled substance and is not generally considered addictive. In this study, we examined quetiapine's dependence potential and abuse liability through animal behavioral tests using rodents to study the mechanism of quetiapine. Molecular biology techniques were also used to find out the action mechanisms of the drug. In the animal behavioral tests, quetiapine did not show any positive effect on the experimental animals in the climbing, jumping, and conditioned place preference tests. However, in the head twitch and self-administration tests, the experimental animals showed significant positive responses. In addition, the action mechanism of quetiapine was found being related to dopamine and serotonin release. These results demonstrate that quetiapine affects the neurological systems related to abuse liability and has the potential to lead psychological dependence, as well.

• Korean Journal of Veterinary Pathology
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• v.5 no.1
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• pp.23-28
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• 2001

This study was conducted to assess the chemopreventive effects of sodium selenite in the rat medium-term multi-organ bioassay using a DMBDD model (DEN+MNU+BBN+DMH+DHPN). Seventy five,6-week-old, male SD rats were divided into 3 groups. The animals in group 1 received DEN(diethylnitrosamine,100 mg/kg bw, single i.p., in saline), MNU (N-methyl-nitrosourea,20 mg/kg bw, i.p.,4 times for 2 weeks), BBN (N-butyl-N-(4-hydroxybutyl) nitrosamine, 0.2% in drinking water for 2 weeks), DMH (1,2-dimethylhydrazine, 40 mg/kg bw, s.c., in saline.4 times (or 2 weeds), and DHPN (N-bis(2-hydroxy-pro-pal)nitrosamine,0.1% in drinking water for 2 weeks), then were placed on sodium selenite (4 ppm in drinking water) for 22 weeks from weeks 4 to 26. The animals in group 2 were given DMBDD alone. The animals in group 3 were given sodium selenite alone. Animals were sacrificed at week 12 for ACF quantitative analysis and at week 26 for tumor induction. The body weights in the group 1 were significantly decreased compared with those of group 2. The tumor multiplicities of large intestine in the group 1 were significantly decreased compared with those of group 2 (P<0.05). These results indicate that sodium selenite may have a potential as chemopreventive agents of colon carcinogenesis.

• Genomics & Informatics
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• v.6 no.3
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• pp.117-125
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• 2008

Recently, obesity has become a worldwide public health concern and the use of anorectic drugs has drastically increased. In this study, sibutramine and phendimetrazine, representative marketed anorectics, were repeatedly administered per os on a daily basis into C57BL/6 mice and the effects of these drugs on food intakes, body weight changes and gene expression profiles were monitored for up to following 7 days. Methamphetamine, which has a potent anorectic effect, was used as a positive control. Anorectic effects were sustained only for two days by phendimetrazine or methamphetamine, but for six days by sibutramine. The modulations of gene expressions in the hypothalamus and the striatum were investigated using microarrays on day 2 and day 7 post-administration, which corresponded to the anorectic period and a return of appetite respectively, for all three drugs tested. Differences in overall gene expression profiles in the stratum on day 2 for sibutramine and phendimetrazine seems to reflect difference between the two in terms of the onsets of drug tolerance. According to microarray findings, the Ankrd26 gene appears to have an important anorectic role, whereas the up-regulation of the olfaction system appeared to be involved in the drug tolerance of anorectics. The microarray data presented in this study demonstrates the usefulness of gene expression analysis for gathering information on the efficacy and safety of anorectic drugs.

• Journal of Embryo Transfer
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• v.26 no.4
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• pp.297-304
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• 2011

Polybrominated diphenyl ethers (PBDEs) are a class of "brominated" (bromine containing) man-made chemicals used as flame retardant additives in plastics, foams, and textiles. PBDEs are found in various environmental contaminants in air, soil, sediment, and water, and 209 individual forms (congeners) of PBDE exist. Among these, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is the dominant congener found in the environment. Exposure to BDE-47 is now worldwide, and levels of BDE-47 have been detected in the blood of animals, including humans. BDE-47 can adversely affect the developmental system in both humans and animals. BDEs have structural similarities to polychlorinated biphenyls and thyroid hormones. However, recent studies have shown that BDEs may act as hormonal disrupting chemicals with detrimental effects. Therefore, a reliable assessment of BDE-47 toxicological action is required to understand the detrimental impacts of BDE-47 on human health. In this review, we overview recent studies on the distribution and potential toxicological effects of BDE-47 in humans and animals.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.13.1-13.4
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• 2016

An analysis of patients and fatalities due to exposure to polyhexamethylene guanidine (PHMG) shows that PHMG causes mainly lung diseases such as pulmonary fibrosis. However, no research on the other organs has been conducted on this matter yet. So, an in-depth discussion on toxicological techniques is needed to determine whether or not PHMG is toxic to organs other than just the lungs. For the test of target organ toxicity by PHMG exposure, a toxicokinetic study must first be conducted. However, measurement method for PHMG injected into the body has not yet been established because it is not easy to analyze polymer PHMG, so related base studies on analytical technique for PHMG including radio-labeling chemistry must come first. Moreover, research on exposure-biomarker and effect-biomarker must also be conducted, primarily related to clinical application. Several limitations seem to be expected to apply the biomarker study to the patient because much time has passed after exposure to the humidifier disinfectant. It is why a more comprehensive toxicological researches must be introduced to the causality for the victims.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.8 no.1
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• pp.23-35
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• 2002

This study was carried out to investigate the oral toxicity of HAD in mice. The results were summarized as follows: 1. HAD did not induced any toxicological effect in the body weight changes of mice. 2. HAD(2.5g/kg, 0.25g/kg) treated group were increased as compared with control group in the hematological values of mice. 3. ALT, AST, BUN, creatinine, CPK were not increased in HAD(2.5g/kg, 0.25g/kg) treated group as compared with control group in the serological values of mice. 4. Brain, Heart, Liver, Spleen, Kidney's weight were not increased in HAD(2.5g/kg, 0.25g/kg) treated group as compared with control group in the organ's weight of mice. 5. HAD(2.5g/kg, 0.25g/kg) treated group did not induced any toxicological effect in the gross findings in mice's any organs. 6. HAD(10g/kg , 5g/kg, 2.5g/kg, 1.25g/kg) treated group did not induced any toxicological effect in the histopathological findings in mice's any organs. 7. HAD(2.5g/ kg, 0.25g/ kg) treated group did not induced any toxicological effect in the histopathological findings in mice's any organs. From above results, HAD has not toxicological effects to mice.

• YAKHAK HOEJI
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• v.42 no.4
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• pp.422-430
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• 1998

In order to study the effects of Rhei rhizoma, Ephedrae herba and Scutellariae radix on hepatic metabolism, we examined the pretreatment effect of those on the metabolism of 7-e thoxycoumarin (EC). Water extracts (1g/kg) of Rhei rhizoma, Ephedrae herba and Scutellariae radix were administered orally to rats for 7 days, respectively. Livers were then isolated and perfused with 100mcM EC for 2 hours. The metabolites of EC, 7-hydroxycoumarin, sulfate conjugate and glucuronide conjugate were measured in the perfusates. The amount of glucuronide conjugates was decreased in Rhei rhizoma pretreated rats (p<0.01), however, 7-hydroxycoumarin was increased in Ephedrae herba pretreated rats (p<0.01). We examined whether the change of enzyme activity is related to the change of cytochrome P4501A1 and P4502B1 mRNA level in the perfused rat liver, which are responsible for EC metabolism. CYP1A1 and CYP2B1 mRNA level was increased, which was was not statistically significant with rhei rhizoma nor ephedrae herba pretreatment. We also assessed the hepatotoxicity of Rhei rhizoma, Ephedrae herba and Scutellariae radix. The activities of ALT and AST were assayed at 24 hours after 7 days administration. Only the ratio of ALT over AST was increased in ephedrae herba pretreated rats (p<0.05). Lipid peroxidation was increased in Rhei rhizoma treatment (p<0.05), while histopathological examination performed after liver perfusion did not show any difference compared with vehicle treatment. These results suggest that Ephedrae herba pretreatment increases the o-deethy-lation of 7-ethoxycoumarin in rats, which may be mediated by CYP1A1 mRNA induction.

• Environmental Mutagens and Carcinogens
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• v.26 no.4
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• pp.125-132
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• 2006

Previous studies showed that epigallocatechin gallate(EGCG) have substantial effects of suppressing the N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)-initiated cell transformation process on the bases of foci formation frequency and loss of anchorage dependency. In this study we tried to clarify the molecular mechanism of suppressing the cell transformation process. Mouse cell line balb/c 3T3 A31-1-1 was exposed 2 days to MNNG followed by 15 days 12-O-tetradecanoylphorbol-13-acetate(TPA) treatment for our transformation process. EGCG was added after the time point of 24 hours exposure to TPA and incubated for 19 days. 2029 genes were selected in our transformation process that showed fold change value of 1.5 or more in the microarray gene expression analysis covering the mouse full genome. These genes were found to be involved mainly in the cell cycle pathway, focal adhesion, adherens junction, TGE-$\beta$ signaling, apoptosis, lysine degradation, insulin signaling, ECM-receptor interaction. Among the genes, we focused on the 631 genes(FC>0.5) reciprocally affected by EGCG treatment. Our study suggest that EGCG down-regulate the gene expressions of up stream signaling factors such as nemo like kinase with MAPK activity and PI3-Kinase, Ras GTPase and down stream factors such as cyclin D1, D2, H, T2, cdk6.

• Biomolecules & Therapeutics
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• v.15 no.2
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• pp.102-107
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• 2007

Cimetidine, a substrate for P-glycoprotein (P-gp), is a well known drug interacting with a variety of drugs and results in alteration of pharmacokinetic parameters by concomitant administration. The aim of present study was to investigate whether cimetidine affects the transport of various quinolone antibiotics in human colorectal cancer cell line (Caco-2) system which has been typically used to investigate drug transport via P-gp. The apparent permeability coefficients (P$_{app}$) value of 9 quinolone antibiotics in the co-treatment with cimetidine was examined. Apical to basolateral (AP-to-BL) transport of fleroxacin in the co-treatment with cimetidine was increased to 1.5-fold (p<0.01) compared with that of fleroxacin alone, whereas basolateral to apical (BL-to-AP) transport of fleroxacin was decreased to 0.83-fold significantly (p<0.05). Ofloxacin was decreased to 0.8-fold (p<0.01) and 0.72-fold (p<0.01) significantly in AP-to-BL and BL-to-AP direction, respectively by cimetidine cotreatment. The P$_{app}$ values of gatifloxacin, moxifloxacin, ciprofloxacin and rufloxacin also were changed by cimetidine. These results have a potential that cimetidine influences on the pharmacokinetics of quinolone antibiotics. It suggests that careful drug monitoring and dosage adjustment may be necessary during the co-administration of quinolone antibiotics with cimetidine.