• 대한한방소아과학회지
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• 제29권3호
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• pp.65-79
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• 2015

Objectives : In this study, effects of haepyoijintang (HIJ) on the increase in airway epithelial mucosubstances of rats and ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells were investigated. Methods : Hypersecretion of airway mucus was induced by exposure of rats to $SO_2$ during 3 weeks. Effect of orally-administered HIJ during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats was evaluated using histopathological analysis after staining the epithelial tissue with PAS-alcian blue. Possible cytotoxicity of HIJ was evaluated by examining the potential damage of kidney and liver functions by measuring serum GOT/GPT activities and serum BUN and creatinine concentrations of rats and the body weight gain during experiment, after administering HIJ orally. At the same time, the effect of HIJ on ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of HIJ and treated with ATP ($200{\mu}M$), PMA (10 ng/ml), EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24 hrs, to evaluate the effect of HIJ both on ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). Results : (1) HIJ decreased the amount of intraepithelial mucosubstances of trachea of rats. (2) HIJ did not show renal and hepatic toxicities and did not affect body weight gain of rats during experiment. (3) HIJ significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions from NCI-H292 cells. (4) HIJ significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin gene expression from NCI-H292 cells. Conclusions : The result from the present study suggests that HIJ might control the production and gene expression of airway mucin observed in various respiratory diseases accompanied by mucus hypersecretion and do not show in vivo toxicity to liver and kidney functions after oral administration. Effect of HIJ with their diverse components should be further investigated using animal experimental models that can reflect the pathophysiology of airway diseases through future studies.

• 대한한방소아과학회지
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• 제27권1호
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• pp.69-81
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• 2013

Objectives In this study, effects of Macmundongtang (MMT) on ATP or TNF-${\alpha}$ or PMA or EGF induced MUC5AC mucin production and gene expression from human airway epithelial cells and the increase in airway epithelial mucosubstances of rats were investigated. Materials and Methods Confluent NCI-H292 cells were pretreated for 30min in the presence of MMT and treated with ATP ($200{\mu}M$) or PMA (10 ng/ml) or EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24hrs, to assess the effect of MMT both on ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). At the same time, hypersecretion of airway mucus was induced by exposure of rats to SO2 during 3 weeks. Effect of orally-administered MMT during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats was assesed using histopathological analysis after staining the epithelial tissue with PAS-alcian blue. Possible cytotoxicity of MMT was assessed by investigating the potential damage of kidney and liver functions by measuring serum GOT/GPT activities and serum BUN concentration of rats and the body weight gain during experiment, after administering MMT orally. Results (1) MMT did not only inhibit but also increased MUC5AC mucin productions and expression levels of MUC5AC gene from NCI-H292 cells. (2) MMT did not decrease the amount of intraepithelial mucosubstances of trachea of rats. (3) MMT did not show renal and hepatic toxicities and did not affect body weight gain of rats during experiment. Conclusions The result from the present study suggests that MMT might normalize the production and gene expression of airway mucin observed in various respiratory diseases accompanied by yin-deficiency, without in vivo toxicity to liver and kidney functions after oral administration.

• Toxicological Research
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• 제21권4호
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• pp.339-345
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• 2005

Aflatoxins are produced by Aspergillus flavus, parasiticus that grows in improperly stored cereals. Aflatoxin $B_1\;(AFB_1)$ is a potent hepatocarcinogen in a variety of experimental animals including human beings. In spite of a high attention to the hepatocarcinogenecity of aflatoxins, the relative toxicity of other types $(AFB_2,\;AFG_1\;and\;AFG_2)$ of the toxins is not fully clarified. Sprague-Dawley male rats were orally administered with $AFB_1,\;AFB_2,\;AFG_1\;and\;AFG_2$ at the dose of 250, 1250, and $2500\;{\mu}g/kg$ body weight. Animals were then killed at 12, 24 or 48 hrs following aflatoxin adminstration. Subsequently the relative weight of liver was measured and histopathological examination on the liver was performed. Level of 8-OxodG and expression of ras gene in the liver was determined. The relative liver weights at high doses of $AFB_1\;and\;AFG_1$ was significantly low. The treatment of $AFB_1$ at the high dose of $2500\;{\mu}g/kg$ showed vacuolar degeneration and centrilobular hepatic necrosis with inflammatory cells. The pathological changes by $AFB_2\;AFG_1,\;and\;AFG_2$ were not clearly found. The formation of 8-OxodG by $AFB_1$ increased in a dose-dependent manner up to 24 hrs after a single treatment of $AFB_1$ thereafter decreased to the level of the control. The treatments of $AFB_2\;AFG_1,\;and\;AFG_2$ showed an inconsistent pattern in the formation of 8-OxodG in the liver of rats with increasing time. The expression of ras oncogene in the liver by $AFB_1$ at the dose of $1250\;{\mu}g/kg$ was increased twice compared to the control. The treatments of $AFB_2\;AFG_1,\;and\;AFG_2$ at all doses decreased the expression of ras in the liver. These results in the present study indicate that $AFB_1$ among aflatoxins with low comparable levels is the most toxic as determined by early biomarkers such as 8-OxodG formation and ras expression. However, the levels of 8-OxodG and ras as biomarkers were not useful to predict the relative hepatocarcinogenicity of aflatoxins to $AFB_1$ in the present model. Further studies are required to look for other biomarkers to predict carcinogenic potency of aflatoxins.

• Molecular & Cellular Toxicology
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• 제2권4호
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• pp.236-243
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• 2006

Microarray analysis of gene expression has become a powerful approach for exploring the biological effects of drugs, particularly at the stage of toxicology and safety assessment. Acetaminophen (APAP) has been known to induce necrosis in liver, but the molecular mechanism involved has not been fully understood. In this study, we investigated gene expression changes of APAP using microarray technology. APAP was orally administered with a single dose of 50 mg/kg or 500 mg/kg into ICR mice and the animals were sacrificed at 6, 24 and 72 h of APAP administration. Serum biochemical markers for liver toxicity were measured to estimate the maximal toxic time and hepatic gene expression was assessed using high-density oligonucleotide microarrays capable of determining the expression profile of >30,000 well-substantiated mouse genes. Significant alterations in gene expression were noted in the liver of APAP-administered mice. The most notable changes in APAP-administered mice were the expression of genes involved in apoptosis, cell cycle, and calcium signaling pathway, cystein metabolism, glutatione metabolism, and MAPK pathway. The majority of the genes upregulated included insulin-like growth factor binding protein 1, heme oxygenase 1, metallothionein 1, S100 calcium binding protein, caspase 4, and P21. The upregulation of apoptosis and cell cycle-related genes were paralleled to response to APAP. Most of the affected gene expressions were returned to control levels after 72 hr. In conclusion, we identified potential hepatotoxicity makers, and these expressions profiling lead to a better understanding of the molecular basis of APAP-induced hapatotoxicity.

• 약학회지
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• 제40권6호
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• pp.727-733
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• 1996

2-(Allylthio)pyrazine is effective in selectively suppressing constitutive and inducible expression of cytochrome P450 2E1. The effect of 2-(allylthio)pyrazine against potentiat ed chemical injury was studied in rats. Vitamin-A pretreatment of rats substantially increased carbon tetrachloride hepatotoxicity, as supported by an ~4-fold increase in serum alanine aminotransferase (ALT) activity. Concomitant pretreatment of rats with 2-(allylthio)pyrazine at the daily dose of 200mg/kg resulted in a 76% decrease in vitamin-A-potentiated hepatotoxicity, which supported the possibility that 2-(allylthio)pyrazine protects the liver against chemical-induced hepatic injury by the mechanism associated with Kupffer cell inactivation. Pyridine pretreatment caused substantial enhancement in carbon tetrachloride hepatotoxicity. 2-(Allylthio)pyrazine treatment of rats reduced the pyridine-potentiated toxicity in a dose-dependent manner. Animals treated with both pyridine and 2-(allylthio)pyrazine prior to intoxicating dose of CCl$_4$ resulted in 85% and 47% decreases in pyridine-increased triglycerides and cholesterol levels in the liver. The protective effect of 2-(allylthio)pyrazine on the DNA strand breakage induced by benzenetriol was assessed by measuring the conversion of supercoiled ${\Phi}x$-174 DNA to the open relaxed form. 2-(Allylthio)pyrazine blocked the benzenetriol-induced conversion of supercoiled DNA to open circular form in a dose-dependent manner. The presence of 2-(allylthio)pyrazine at the doses from I to 10mM in the incubation mixture containing 5 ${\mu}$M benzenetriol completely protected benzenetriol-induced DNA strand breakage with the EC50 for the 2-(allylthio)pyrazine blocking being noted as ~220 ${\mu}$M, whereas allyl disulfide exerted protecting effect at relatively high concentrations (i.e. ~850 ${\mu}$M), suggesting that 2-(allylthio)pyrazine effectively scavenges the reactive oxygen species. These results provide evidence that 2-(allylthio)pyrazine blocks vitamin A- or pyridine-potentiated CCl$_4$ hepatotoxicity and that the agent is active in protecting DNA by scavenging the reactive oxygen species.

• 한국산학기술학회논문지
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• 제21권10호
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• pp.231-239
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• 2020

본 연구의 목적은 TCDD로 인해 발생하는 산화적 스트레스에 대한 GYB의 내분비 기능 및 항산화 효능에 미치는 영향을 평가하기 위한 것이다. 2017년도에, 산화적 스트레스에 대한 GYB의 효능을 평가하기 위해 35마리의 수컷 SD랫드를 5개의 그룹으로 나누어 실험하였다. 정상 대조군은 vehicle 및 saline을 투여하였으며, TCDD 단독투여그룹은 TCDD(2 ㎍/kg, weeks) 및 생리식염수를 복강 내 투여하였으며, 시험 군은 6주 동안 GYB (75, 150, 300 mg/kg)를 3가지 농도로 나누어 경구로 투여하였다. 체중은 NC 그룹의 랫드와 비교하였을 때 TCDD 노출 후 6주 후에 유의하게 감소하였다(p<0.001). 그러나 TCDD에 의한 체중 감소는 GYB 300 mg/kg 투여에 의해 현저하게 보호되었다(p<0.01). TCDD로 유도된 랫드의 간은 세포질의 공포 변성이 나타났으며, 간의 동양 혈관과 중량의 증가를 나타냈다. MDA, SOD를 측정한 결과, TCDD 투여에 의하여 두 항목 모두 감소하는 경향이 나타났다. 반면, GYB 투여에 의한 변화는 나타나지 않았고, SOD 결과에서 GYB 300군에서 NC군 대비 유의성이 관찰(p<0.05) 되었다. 이러한 발견은 GYB가 랫드에서 TCDD 유도 간 독성에 대해 보호 효과를 가질 수 있음을 증명하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10949-10955
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• 2015

Liver cancer is one of leading digestive malignancies with high morbidity and mortality. There is an urgent need for the development of novel therapies for this deadly disease. It has been proven that asparagus polysaccharide, one of the most active derivates from the traditional medicine asparagus, possesses notable antitumor properties. However, little is known about the efficacy of asparagus polysaccharide as an adjuvant for liver cancer chemotherapy. Herein, we reported that asparagus polysaccharide and its embolic agent form, asparagus gum, significantly inhibited liver tumor growth with transcatheter arterial chemoembolization (TACE) therapy in an orthotopic hepatocellular carcinoma (HCC) tumor model, while significantly inhibiting angiogenesis and promoting tumor cell apoptosis. Moreover, asparagine gelatinous possessed immunomodulatory functions and showed little toxicity to the host. These results highlight the chemotherapeutic potential of asparagus polysaccharide and warrant a future focus on development as novel chemotherapeutic agent for liver cancer TACE therapy.

• Journal of Nutrition and Health
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• 제24권6호
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• pp.526-533
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• 1991

식이 셀렌이 납섭취에 따른 흰주의 혈액 및 간장중의 $\delta$-Aminolevulinic Acid Dehydratase(ALAD)활성 저해에 미치는 영향을 알아보기 위하여 체중이 141$\pm$5g이 되는 Sprague-Dawley 종 숫쥐를 식이내 납함량을 0(대조군), 200, 1,000, 2,000, 5,000ppm으로 달리하고, 다시 0.5ppm의 셀렌을 첨가한군과 비첨가군등 9군으로 나누어 4주간 사육한 후 체중증가, 식이효율, 혈중hemoglobin, hematocrit치, 혈액 및 간장중의 ALAD 효소활성, 그리고 뇨증 aminolevulinic acid(ALA)의 배설량을 측정한 결과는 다음과 같다. 1. 식이섭취량은 대조군과 납식이군과 별 차이가 없었고, 식이효율 및 체중증가량은 2,000, 5,000 ppm 납식이군이 유의적으로 낮았으나, 셀렌을 첨가했을 때는 대조군과 차이가 없었다. 2. 장기의 무게는 200, 1,000ppm 납식이군에서 신장의 무게가 대조군에 비해 비대했으나, 셀렌을 첨가했을때는 타실험군과 차이가 없었다. 3. Hemoglobin 함량과 hematocrit치는 납함량이 높을수록 대조군에 비해 감소하였으나, 납함량이 1,000, 2,000ppm군에서는 셀렌을 첨가했을때 비첨가군에 비해 증가되었다. 4. 혈액중 ALAD효소 활성은 납함량이 증가될수록 대조군에 비해 ALAD활성이 현저히 감소되었고 200, 1,000, 2,000ppm 군에서는 셀렌을 첨가했을때 비첨가군에 비해 그 활성이 증가되었다. 간장중의 ALAD효소 활성도 혈액에서와 같은 경향으로 납함량이 즐가될수록 감소되었으나, 혈액에서 보다는 ALAD 활성 감소가 적었으며 셀렌을 첨가한 경우 모든 식이군에서 비첨가군에 비래 ALAD 활성이 증가되었다. 5. 뇨중의 ALA 배설량은 ALAD활성과는 반대로 식이내 납함량이 높을수록 그 배설량이 증가되었고, 셀렌 첨가군에서는 그 배설량이 감소되었다.

• 대한한방소아과학회지
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• 제30권2호
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• pp.31-46
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• 2016

Objectives In this study, the effects of Ja-eum-gang-hwa-tang (JGT) on the increase in airway epithelial mucosubstances of rats and ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells were investigated. Materials and Methods Hypersecretion of airway mucus was produced by exposure of $SO_2$ to rats for 3 weeks. The effect of orally-administered JGT for 2 weeks on increased epithelial mucosubstances from tracheal goblet cells of rats was assessed by using histopathological analysis after staining the epithelial tissue with Hematoxylin-eosin and PAS-alcian blue. Possible cytotoxicity of JGT was assessed by investigating the potential damage on kidneys and liver functions by measuring serum GOT/GPT activities and serum BUN concentration of rats and the body weight gain during experiment. Also, the effect of JGT on ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of JGT and treated with ATP ($200{\mu}M$) or PMA ($10ng/ml$) or EGF ($25ng/ml$) or TNF-${\alpha}$ (0.2 nM) for 24 hrs to assess the effect of JGT both on ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production by using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). Results (1) JGT decreased the amount of intraepithelial mucosubstances of trachea of rats. (2) JGT did not show any renal and hepatic toxicities, and did not affect body weights either. (3) JGT significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions from NCI-H292 cells. (4) JGT inhibited EGF-, and PMA-induced expression levels of MUC5AC gene in NCI-H292 cells. However, ATP- and TNF-${\alpha}$-induced MUC5AC gene expression levels were not affected in NCI-H292 cells. Conclusions The result from the present study suggests that JGT might control the production and gene expression of airway mucin observed in various respiratory diseases which accompanied by mucus hypersecretion. Also, JGT did not show liver toxicity or impact on kidney functions. The effect of JGT should be further studied by using animal experimental models which can show proper pathophysiology of airway diseases.

• Applied Microscopy
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• 제32권3호
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• pp.231-246
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• 2002

[ $CdCl_2$ ]이 간에 미치는 독성에 관한 Squalene의 효과를 알아보기 위하여 30 mg 내외의 웅성 ICR계 mouse에 체중 kg당 5.0 mg의 $CdCl_2$와 체중 kg당 180.0 mg의 SQ를 복강투여하여 1, 2, 3, 4, 5, 6, 7일째에 절취한 간조직을 SOD 활성도와 투과전자현미경법을 이용하여 관찰한 결과 다음과 같은 결론을 얻었다. 간조직에서 SOD 활성도는 Group A가 정상군에 비해 증가를 보였고, Group B는 Group A에 비해 약간의 감소를 나타내었다. 조직학적 관찰에서 Group A의 핵은 불규칙한 모양이 관찰되었고, 미토콘드리아의 내강 팽대와 cristae 파괴가 나타났으며, 조면소포체의 수조 팽대가 관찰되었다. Group B의 핵은 원형을 나타내었으며 미토콘드리아는 약간 팽대되었지만 정상적인 형태를 보였고, 조면소포체의 전형적인 층판구조가 관찰되었다. 이상의 결과를 종합하면 SQ 처치가 SOD 활성을 감소시키고 mouse 간세포에 미치는 카드뮴의 독성을 감소시켜 간세포의 회복에 효과가 있는 것으로 사료된다.