• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.141-149
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• 2006

Tamoxifen (TAM), a non-steroidal anti estrogen anticancer drug and chemopreventive agent for breast cancer, have caused cholestasis in liver. The potent hepatocarcinogenicity of this drug has been reported. Methotrexate (MTX) is dihydrofolate reductase inhibitor which interfaces with the synthesis for urine nucleotide and dTMP. And it may cause atrophy, necrosis and steatosis in liver. These two anticancer drug have well-known hepatotoxicity. So, in this study we compare the gene expression pattern of antitumor agent TAM and MTX, using the cDNA microarray. We have used 4.8 K cDNA microarray to identify hepatotoxicity-related genes in 5-week-old male Sprague-Dawley (SD) rats. Confirm the pattern of gene expression, we have used Real time PCR for targeted gene. In the case of MTX, Protease related gene (Ctse, Ctsk) and Protein kinase (Pctk 1) have shown specific expression pattern. And in the case of TAM, apoptosis related gene (Pdcd 8) and signal transduction related gene (kdr) have significantly up regulated during treatment time. Gene related with growth factor, lipid synthesis, chemokins were significantly changed. From the result of this study, the information about influence of TAM and MTX to hepatoxicity will provide.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.20 no.3
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• pp.29-42
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• 2007

Objectives : Allergic rhinitis is an inflammation or irritation of the mucous membranes that in the nose. Common symptoms include sneezing; a stuffy or runny nose; itch eyes, nose and throat; and watery eyes. We aimed to determine therapeutic effect of Onpye-tang by observing changes in blood cells and the nasal mucosal tissue. Methods : Twenty-four Sprague-Dawley rats were divided into three groups: normal, control, and sample group. Allergic rhinitis was induced in the control and sample group by intraperitoneal and intranasal sensitization with 0.l% Ovalbumin solution. Then Onpye-tang was orally administered only to the sample group for 28days, while the rats in the control group was given normal saline. We observed changes in the number of RBC and WBC; changes of neutrophils, lymphocyte, monocyte, and eosinophil proportions; total IgE level and AST & ALT change; also, changes in the nasal mucosal tissue. We used Student T-test statistically(p<0.05). Results : Onpye-tang showed significantly decreased IgE level on the serum of the rat model. Onpye-tang showed significantly decreased eosinophil level on the blood of the rat model. Onpye-tang inhibited the inflammatory reaction on the nasal mucosal tissue, according to nasal mucosal biopsy. Onpye-tang showed an inhibitory effect on the process of allergic rhinitis, according to IgE level, Eosinophil level, nasal mucosal biopsy. Onpye-tang had no hepatoxicity, according to AST and ALT on the serum. Conclusion : According to the above results, it is considered that Onpye-tang has an inhibitory effect on the process of allergic rhinitis and it can be used in relieving symptoms of allergic rhinitis.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.26 no.2
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• pp.119-138
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• 2016

Objectives: The purpose of this study is to review size, shape, and crystal structure-dependent toxicity of major metal oxide particles such as silicon dioxide, tungsten trioxide, aluminum oxide, and titanium dioxide as byproducts generated in semiconductor fabrication facility. Methods: To review the toxicity of major metal oxide particles, we used various reported research and review papers. The papers were searched by using websites such as Google Scholar and PubMed. Keyword search terms included '$SiO_2$(or $WO_3$ or $Al_2O_3$ or $TiO_2$) toxicity', 'health effects $SiO_2$(or $WO_3$ or $Al_2O_3$ or $TiO_2$). Additional papers were identified in references cited in the searched papers. Results: In various cell lines and organs of human and animals, cytotoxicity, genotoxicity, hepatoxicity, fetotoxicity, neurotoxicity, and histopathological changes were induced by silicon dioxide, tungsten trioxide, aluminium oxide, and titanium dioxide particles. Differences in toxicity were dependent on the cell lines, organs, doses, as well as the chemical composition, size, surface area, shape, and crystal structure of the particles. However, the doses used in the reported papers were higher than the possible exposure level in general work environment. Oxidative stress induced by the metal oxide particles plays a significant role in the expression of toxicity. Conclusions: The results cannot guarantee human toxicity of the metal oxide particles, because there is still a lack of available information about health effects on humans. In addition, toxicological studies under the exposure conditions in the actual work environment are needed.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.18 no.3
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• pp.55-65
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• 2005

Objectives: Allergic rhinitis is an inflammation or irritation of the mucous membranes that line the nose. Common symptoms include sneezing; a stuffy or runny nose; itchy eyes, nose and throat; and watery eyes. We aimed to determine therapeutic effects of Gudambope-tang by observing changes in blood cells and the nasal mucosal tissue. Methods: Fifteen Spraque-Dawley rats were divided into three groups: normal, control, and sample group. Allergic rhinitis was induced in the control and sample group by intraperitoneal and intranasal sensitization with 0.1% ovalbumin solution. Then Gudambope-tang was orally administered only to the sample group for 28days, while the rats in the control group was given normal saline. We observed changes in the number of RBC and WBC; changes of neutrophil, Iymphocyte and monocyte proportions; total IgE level and AST & ALT changes; also, changes in the nasal mucosal tissue. We used ANOVA test statistically(p<0.05). Results: 1. Gudambope-tang showed an inhibitory effect on the process of allergic rhinitis. 2. Gudambope-tang inhibited the inflammatory reaction on the nasal mucosal tissue. 3. Gudambope-tang had no hepatoxicity. Conclusions: According to the above results. it is considered that Gudambope-tang has an inhibitory effect on the process of allergic rhinitis and it can be used in relieving symptoms of allergic rhinitis.

• Toxicological Research
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• v.35 no.4
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• pp.295-301
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• 2019

In this review, we describe the absorption rates (Caco-2 cell permeability) and hepatic/plasma pharmacokinetics of 53 diverse chemicals estimated by modeling virtual oral administration in rats. To ensure that a broad range of chemical structures is present among the selected substances, the properties described by 196 chemical descriptors in a chemoinformatics tool were calculated for 50,000 randomly selected molecules in the original chemical space. To allow visualization, the resulting chemical space was projected onto a two-dimensional plane using generative topographic mapping. The calculated absorbance rates of the chemicals based on cell permeability studies were found to be inversely correlated to the no-observed-effect levels for hepatoxicity after oral administration, as obtained from the Hazard Evaluation Support System Integrated Platform in Japan (r = -0.88, p < 0.01, n = 27). The maximum plasma concentrations and the areas under the concentration-time curves (AUC) of a varied selection of chemicals were estimated using two different methods: simple one-compartment models (i.e., high-throughput toxicokinetic models) and simplified physiologically based pharmacokinetic (PBPK) modeling consisting of chemical receptor (gut), metabolizing (liver), and central (main) compartments. The results obtained from the two methods were consistent. Although the maximum concentrations and AUC values of the 53 chemicals roughly correlated in the liver and plasma, inconsistencies were apparent between empirically measured concentrations and the PBPK-modeled levels. The lowest-observed-effect levels and the virtual hepatic AUC values obtained using PBPK models were inversely correlated (r = -0.78, p < 0.05, n = 7). The present simplified PBPK models could estimate the relationships between hepatic/plasma concentrations and oral doses of general chemicals using both forward and reverse dosimetry. These methods are therefore valuable for estimating hepatotoxicity.

• Journal of Society of Preventive Korean Medicine
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• v.11 no.2
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• pp.23-39
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• 2007

Objectives : The aim of this study was to evaluate effects of herbal medicine and other associated factors for abnormal liver function tests(especially total bilirubin, AST, ALT, and ${\gamma}GT$) levels in outpatients at an oriental medical clinic. Methods : A cross-sectional study based on clinical records was conducted on 1,871 patients at one Oriental medical clinic in Seoul, Korea. 504 patients received a liver function tests for screening and 497 patients ranging from the age of 4 to 74 were chosen for the study. Patients with basal liver disease or DM were excluded during the screening process. Patients were classified into case(abnormal) and control(normal) groups by normal liver function test references. Results and Conclusions : In this study, 33.0% of the patients were females, and 67.0% were males. The mean age was $34.7{\pm}11.9$ years old. The mean total protein value was $6.78{\pm}0.66g/dL$(male $6.79{\pm}0.61$, female $6.76{\pm}0.76$), albumin $3.89{\pm}0.50g/dL$(male $3.94{\pm}0.47$, female $3.81{\pm}0.54$), total bilirubin $0.51{\pm}0.35mg/dL$(male $0.54{\pm}0.39$, female $0.45{\pm}0.23$), AST $23.31{\pm}18.22U/L$(male $26.37{\pm}20.73$, female $17.09{\pm}8.72$), ALT $33.49{\pm}36.36U/L$(male $40.56{\pm}41.77$, female $19.13{\pm}12.64$), LDH $258.07{\pm}74.84mg/dL$(male $263.68{\pm}73.77$, female $246.70{\pm}75.92$), and ${\gamma}GT$ $39.64{\pm}59.16U/L$(male $50.15{\pm}69.43$, female $17.83{\pm}8.36$). The percentage of abnormal total bilirubin levels(>1.0) in these patients was 2.6%, abnormal AST levels(>39m, >29f) 8.5%, ALT levels(>47m, >32f) 18.8%, and ${\gamma}GT$ (>50m, >40f) 19.9%.

• Journal of Society of Preventive Korean Medicine
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• v.12 no.2
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• pp.61-72
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• 2008

Objectives : The aim of this study was to evaluate effects of herbal medicine and other associated factors for abnormal liver function tests(especially total bilirubin, AST, ALT, and ${\gamma}$GT) levels in outpatients at an oriental medical clinic. Methods : A cross-sectional study based on clinical records was conducted on 504 patients at one Oriental medical clinic in Seoul, Korea. They were tested a liver function tests for screening and 497 patients ranging from the age of 4 to 74 were chosen for the study. Patients with basal liver disease or DM were excluded during the screening process. Patients were classified into case(abnormal) and control(normal) groups by normal liver function test references. Results and Conclusions : In this study, Significant correlations for abnormal total bilirubin levels was age, for abnormal AST was gender, for abnormal ALT were gender, smoking, marriage status, and job, for abnormal ${\gamma}$GT were age, gender, obesity, alcohol, smoking, marriage status, and job using the Chi-square test(p<0.05). There was no significant correlations for abnormal LFTs by using herbal medication history, and intake duration. After controlling other covariates, logistic regression analysis showed that the significant associated factors for abnormal total bilirubin levels were age(odds ratio[OR]=0.87, 95% confidence intervals [CI]=0.87-0.99). For abnormal AST levels was obesity(OR=2.45, CI=1.2-4.9), for abnormal ALT levels were age(OR=1.01, CI=0.99-1.03), male gender(OR=3.31, CI=1.62-6.76), and obesity(OR=3.71 CI=2.28-6.08). For abnormal ${\gamma}$GT levels were male gender(OR=4.83 CI=1.34-17.43), obesity(OR=3.29, CI=1.74-6.22), alcohol (OR=2.51, CI=1.19-5.28), and smoking(OR=2.29, CI=1.16-4.50). Herbal medication history was not as a risk factor for all abnormal liver function tests. Therefore, people who are male, obese, alcohol drinker and smoker will have higher liver function test levels. But intake of herbal medication or the duration of intake may not be the risk factor for abnormal liver function test results.

• Herbal Formula Science
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• v.25 no.1
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• pp.11-28
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• 2017

Objectives : The contents of aconitine in aconiti radix lateralis preparata, purified hot water extract of Aconiti Radix lateralis preparata, and purified hot water extract of Sambutang-P that contains Aconiti Radix lateralis preparata was analyzed to compare toxicity. Toxicity of Sambutang-P that contains Aconiti Radix lateralis preparata was assessed with a single oral toxicity test on 6-week-old male and female Sprague-Dawley rats. Methods : 1. The contents of aconitine in Aconiti Radix lateralis preparata, purified hot water extract of Aconiti Radix lateralis preparata, and purified hot water extract of Sambutang-P that contains Aconiti Radix lateralis preparata was analyzed using the purity test according to the "Korean Herbal Pharmacopoeia". 2. 2,000mg/kg was injected for the single oral toxicity test of purified hot water extract of Sambutang-P that contains Aconiti Radix lateralis preparata, and the test was done for a test group (injection) and a control group, each with 5 male and 5 female rats. For 14 days after injection, rats were observed for general symptoms and changes in weight. Afterwards, blood biochemical test, autopsy, and histophathological exam of the liver was conducted. Results : 1. The contents of aconitine was 0.0785% for Aconiti Radix lateralis preparata, 0.1510% for purified hot water extract of Aconiti Radix lateralis preparata, and 0.1248% for purified hot water extract of Sambutang-P that contains Aconiti Radix lateralis preparata. 2. There was no death of either male or female rats in both the control group and the test group (injection of 2,000mg/kg). 3. No unusual symptom was observed in both the control group and the test group (injection of 2,000mg/kg). 4. No significant change in weight was observed for both male and female rats in the test group (2,000mg/kg). 5. The histopathological exam of ALT, AST, ALP, GGT and LDH showed no significant changes for both male and female rats in the test group (2,000mg/kg). 6. According to the autopsy results, no visible abnormality of organs or tissues was found in both the control group and the test group (2,000mg/kg). 7. According to the histopathological exam of the liver, the effect of the injected material was not observed for either male or female rats in the test group (2,000mg/kg). Conclusions : The contents of aconitine in Aconiti Radix lateralis preparata was lower for decoction of Sambutang-P with ginseng radix alba than for decoction of only Aconiti Radix lateralis preparata. This suggests that ginseng radix alba can dilute toxicity of Aconiti Radix lateralis preparata. As for a single oral toxicity test of Sambutang-P that contains Aconiti Radix lateralis preparata, no abnormal reaction was observed even when the injection amount far exceeded a toxic dose or a lethal dose. Thus, it is deemed that using Sambutang-P at a clinically prescribed dose would not lead to hepatoxicity.

• Journal of Life Science
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• v.20 no.1
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• pp.133-141
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• 2010

The protective effect of a mixed powder from solid-cultured and liquid-cultured Lentinus edodes mycelia (2:1, w/w) (designate LED) on the carbon tetrachloride ($CCl_4$)- and ethanol-induced hepatotoxicity of male Sprague-Dawley (SD) rat was investigated. In the $CCl_4$-induced rat hepatotoxicity experiment, rats of 4 groups (6 rats/group) were administere with Normal (0.2 ml distilled water), Control (0.2 ml distilled water), LED (LED 200 mg/kg BW + 0.2 ml distilled water), and Silymarin (200 mg/kg BW + 0.2 ml distilled water), p.o., daily for 2 weeks. Afterwards, all groups except for the Normal group were subjected to abdominal injection with $CCl_4$ ($CCl_4$ : corn oil, 1:1 v/v; 0.5 ml/kg BW). For the ethanol- induced rat hepatotoxicity experiment, rats were divided into 5 groups (5 rats/group): Normal; Pair-fed control (PFC); Control (ethanol); LED (ethanol + LED 200 mg/kg BW); and Silymarin (ethanol + silymarin 200 mg/kg BW). Rats of the Normal and PFC groups were fed a basal liquid diet, and rats of the Control, LED, and Silymarin groups were fed a liquid ethanol diet containing LED or Silymarin. Eight weeks later, blood and liver samples were collected to analyze biomarkers. In $CCl_4$-induced SD rats, LED elevated hepatic superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH peroxidase) activities and thiobarbituric reactive substances (TBARS) were reduced, resulting in the reduction of glutamate-oxalate transaminase (GOT), glutamate-pyruvate transaminase (GPT) and lactic dehydrogenase (LDH) activities in plasma. Similar results of these enzymes and biochemical markers in both liver tissues and plasma were seen in ethanol-induced hepatotoxicity of SD rats. In addition, elevated alcohol dehydrogenase (ADH) activity and reduced expression of cytochrome p450 mixed monooxygenase enzyme (CYP2E1) were seen in liver tissues from ethanol-treated rats by LED treatment. These effects of LED were similar to those of Silymarin. In in vitro experiments, LED showed antioxidant activity in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) system and mouse liver mitochondria system induced by NADPH/$Fe^{2+}$ and cumine hydroperoxide (CuOOH). These results indicate that LED protected SD rat hepatotoxicity, induced by $CCl_4$ and ethanol, through its antioxidative activity and might be useful as a material for protection from hepatoxicity in humans.