포공영 추출물이 흰쥐 간 Xanthine Oxidase 활성에 미치는 영향

이상일,이영순,윤종국 동아시아식생활학회 1995 동아시아식생활학회지 Vol.5 No.3

This study was undertaken to investigate the effect of Taraxacum herba extract on the hepatic xanthine oxidase activity as a oxygen free radical generating enzyme in vitro and in vivo. It was observed that partial purified hepatic xanthine oxidase (type O) activity was strongly inhibited by the addition of Taraxacum herby n-butanol extract in vitro. The K_(m) value of xanthine oxidase without affecting the V_(max) value for xanthine was significantly increased by the addition of Taraxacum herba n-butanol extract (200㎍/㎖) in vitro. It was also observed that hepatic xanthine oxidase (type O) activity was significantly inhibited by the treatment of Taraxacum herba n-butanol extract for 5 days (over 40mg/kg, i.p.), whereas, xanthine oxidase (type D) activity was not changed by the injection of Taraxacum herba n-butanol extract. Meanwhile, liver weight /body weight(%), serum alanine aminotransferase activity and hepatic lipid peroxide content in Taraxacum herba n-butanol extract-treated rat were not changed. These findings led us to conclude that Taraxacum herba n-butanol extract may regulate the hepatic xanthine oxidase type O activity to prevent toxic effect of oxidative stress by the oxygen free radicals.

흰쥐 성장기간에 따른 Xylene의 독성에 관한 연구

이혜자,이상희,전태원,이상일,윤종국 대한의생명과학회 2000 Journal of biomedical laboratory sciences Vol.6 No.3

실험동물에 있어서 연령 차이에 따라서 xylene 독성이 어떠한 차이가 있는지를 검토하는 일환으로 5주령 및 12주령 흰쥐에 50% m-xylene을 체중 100 g 당 0.25 ml씩 1회 투여한 다음 24시간 후에 처치하여 다음과 같은 결과를 얻었다. Xylene 투여로 인한 요 중 methylhippuric acid 함량은 5주령군이 12주령군에 비해 현저하게 높게 나타났다. 그리고 간조직 중 cytochroms P-450 함량은 대조군에 있어서 5주령군이 12주령군 보다 약 50% 정도 낮게 나타났으나 xylene 투여로 인한 cytochrome P-450 함량 증가율은 12주령군 보다 5주령군에서 높게 나타났다. 간 alcohol dehydrogenase 활성치도 대조군에 있어서는 5주령군이 12주령 보다 약 35% 정도 낮게 나타났으나 xylene 투여로 인한 본 효소의 활성 증가율은 5주령군에서 오히려 높게 나타났다. 그러나 간 aldehyde dehydrogenase 활성치는 대조군 및 xylene 투여군 모두 5주령과 12주령간에 유의한 차이를 나타내지 않았다. 한편 xylene 투여시 체중 당 간무게, 간조직 malondialdehyde 함량 및 혈청 ALT 활성 변동을 통하여 간손상 정도를 상호 비교 관찰하였을 때, 12주령군이 5주령 실험동물 보다 간손상이 다소 심하게 나타남을 알 수가 있었다. 이상 실험결과는 연령에 따라 xylene에 의한 간손상의 차이는 이물질의 생체내 대사율이 달리 나타나기 때문일 것으로 생각된다. To evaluate an effect of aging on the xylene toxicity, 50% m-xylene in olive oil (0.25 ml/100 g body wt.) was administered to 5 week and 12 week-old rats one times intraperitoneally and sacrificed at 24 hrs afterwards. The increasing rate of urinary H-methylhippuric acid concentration was higher in 12 week-old rats than 5 week-old rats by the treatment of m-xylene. On the liver function findings, i.e., liver weight/body weight (%), serum levels of ALT activity and hepatic malondialdehyde content, 12 week-old rats showed more severe liver injury than 5 weeks those in xylene-treated rats. And the hepatic cytochrome P-450 contents was higher in 12 weeks rats than those of in 5 week-old rats, but the increasing rate of that was lower in 12 week-old rats. Hepatic alcohol dehydrogenase activity was also higher in 12 week-old rats than in 5 week-old rats whereas the increasing rate of that was higher in 5 week-old than those in 12 week-old rats by the xylene treatment. Furthermore, the hepatic aldehyde dehydrogenase activities were no differences between the 5 and 12 week-old rats both in the control and xylene-treated group, In conclusion, age may influences upon the hepatotoxicity with xylene and it may be responsible for xylene metabolism in rats.

랫드에 있어서 Bromobenzene의 격일 투여 시, 매일 투여한 경우와 간손상 정도의 비교

이상희,윤종국,조현국 대한의생명과학회 2000 Journal of biomedical laboratory sciences Vol.6 No.2

Bromobenzene의 투여 간격에 따라 간손상이 어떠한 차이를 나타내는지를 검토하기 위하여 흰쥐에 체중 1kg 당 400mg의 bromobenzene을 복강으로 2일 및 1일 간격으로 각각 3회 투여한 다음 간손상을 병리조직학적, 간기능적 측면에서 검토한 결과 2일 간격으로 투여한 실험군에서 간손상이 경미하게 나타났다. 그리고 간조직 중 cytochrome P450 함량은 2일 간격으로 투여한 실험군에서는 대조군 보다 증가되는 경향을 보였으나 1일 간격으로 투여한 경우에는 대조군 보다 오히려 유의한 (p<0.01) 감소를 보였다. 간조직 중 대조군에 대한 glutathione 감소율과 glutathione S-transferase 활성 증가율은 2일 간격으로 bromobenzene을 투여한 군이 1일 간격으로 투여한 실험군 보다 높게 나타났다. 이상 실험 결과는 동일한 양과 회수로서 bromobenzene을 격일로 투여한 실험동물에 있어서 매일 투여한 경우 보다 간손상이 경미하였으며, 이는 bromobenzene의 대사율이 증가됨으로서 나타난 결과로 생각된다. To evaluate the effect of intervals of bromobenzene treatment on the liver damage, the bromobenzene(400 mg/kg, i.p.) was given to rats at either one day or two days interval at three times. All the experimental animals were sacrificed at 24 hours after the last injection. Liver morphological changes were observed under a light microscopic examination and liver functional changes were determined by the measurement of alaine aminotransferase (ALT) activity and hepatic malondialdehyde (MDA) content. The experimental to examine the cause of liver damage were cytochrome P450, glutathione (GSH) content and glutathione S-transferase(GST) activities. The results are summarized as follows; Based on the liver morphological and functional findings, the daily bromobenzene-treated rats (ED) showed the more severe liver damage than every other day bromobenzene-treated rats (EOD). The hepatic cytochrome p450 content was higher in EOD group than that in ED group. And the increasing rate of hepatic GST activity and decreasing rate of GSH content to the control were higher in EOD group than that in ED group. In conclusion, the treatment of bromobenzene intermittently to the rats may lead to more reduced liver injury compared with the continuously treated animals when both cases are treated with the same dose and frequency, and it may be caused by the enhancement of bromobenzene metabolism.

Bromobenzene의 투여 횟수에 따른 간독성의 차이

이상희,전태원,윤종국 대한의생명과학회 2000 Journal of biomedical laboratory sciences Vol.6 No.1

실험동물에 있어서 간조직의 손상 정도에 미치는 xenobiotics의 투여기간에 의한 영향을 검토할 목적으로 hepatotoxin의 일종인 bromobenzene의 투여 횟수에 의한 간손상 정도와 이의 기전을 구명 한 결과는 다음과 같다. 횐쥐에 1일 간격으로 bromobenzene (400 mg/kg)을 복강으로 1회, 3회 및 6회 투여 한 실험군을 대상으로 하여 실시한 실험에서 혈청 alanine aminotransferase (ALT)의 확성 및 체중 당 간 무게는 bromobenzene을 1회 투여 한 1일째에는 대조군과 별다른 변동을 볼 수 없었으나 3회 투여 한 3일째에는 유의하게 증가되었으며, 이후 6일째 6회 투여한 실험군에서는 체중 당 간 무게 및 혈청 ALT활성이 3일째 보다 현저히 감소되어 오히려 대조군과 유사하였다. 이와 같이 투여 횟수의 증가에 따른 간손상의 정도가 투여 횟수와 비례하지 않은 것이 어떠한 기전에 의해서 나타나는지를 구명하기 위해 bromobenzene 대사에 관여 하는 간조직 중 aniline hydroxylase 및 glutathione S-transferase 활성과 glutathione (GSH) 함량을 측정한 결과, 이들 대사효소 및 GSH이용률이 bromobenzene 6회 투여 군에서 1회 및 3회 투여군보다 높게 나타났다. 이상 실험 결과를 종합해 볼 때 어떤 독성물질이 생체에 계속 폭로 시 어느 시점에서 중독현상이 경감되는 것은 이 독성물질의 대사율을 증가시켜 해독하려는 생리적응현상이 일어 날 수 있다는 가설을 제시 할 수 있다. A Study on the Effect of Injection Frequency on the Liver Damage in Rats To investigate the effect of injection frequency of bromobenzene on the liver damage, bromobenzene (400 mg/kg, i.p.) was given daily to rats for six days. All experimental animals were sacrificed at 24 hours after the last injection. Morphological changes of the liver were observed under a light microscopic examination. Functional changes of the liver were evaluated by the measurement of alanine aminotransferase activity. To clarify the cause of discrepancy in liver damage, hepatic glutathione (GSH) content, glutathione S-transferase (GSI) and aniline hydroxylase (AH) activities were determined. In the experiments of daily bromobenzene treatments, the sacrificed animals at six day (6 time-injected animals) showed slighter liver damage than those sacrificed at 3 day (3 time-injected ones), based on the liver morphological or functional findings; the decreasing ratio of GSH content and increasing ratio of liver GST and AH activities in the 6 time-injected group were higher than those in the 3 time-injected one.

도시적 토지자원개발에 있어 민간부문 참여확대방안

이종익,김재국 東新大學校 工業技術硏究所 1998 工業技術硏究 Vol.4 No.-

The main purpose of this paper is to identify the enlargement measures of private sector involvement in the urban land development. To delve into the realities of private land development, this paper is organized into five chapters. To alleviate the problems of the public regulation and monopoly, the private sector should be encouraged to participate the urban land development process. In reality, the enlargement measures of private sector involvement in the pubic sector development can be considered in the present three development systems as follows; the collaboration system between the private and the public sector, the third-sector system and the co-development system among landowners. The former two can be applied to the larger scale development projects while the latter to the smaller ones. In conclusion, the private sector involvement in the urban land development should be enlarged in order not only to combine the vigour of private sector with the public development system but also to meet the diverse needs of the people through the collaboration work between the private and the public sector.

Effect of p-Phenylenediamine Application to Rat Skin on the Liver Oxygen Free Radical Systems

윤종국,--,-- THE KOREAN SOCIETY FOR BIOMEDICAL LABORATORY SCIEN 2003 Journal of biomedical laboratory sciences Vol.9 No.2

To evaluate the influence of hepatic oxygen free radical systems on liver injury by topical p-phenylenediamine (PPD) application on rat skin. PPD (25mg/16.5㎠) was topically applied to the abdominal region 5 times every other day and sacrificed. By PPD treatment, increasing rate of liver weight/body weight(%), serum activities of alanine aminotransferase and aspartate aminotransferase and decreasing rate of microsomal glucose-6-phosphatase activity were higher in the rats fed tungstate supplemented diet than those fed a standard diet. These findings indicate that group fed tungstate supplemented diet have more severe liver injury compared with group fed standard diet on topical PPD application. However, the activities of oxygen free radical generating enzymes such as xanthine oxidase (XO) and cytochrome P450 dependent aniline hydroxylase and those of oxygen free radical scavenging enzymes were not found to be different between these two animal groups. In the present study, a novel monitoring method to detect the generating of oxygen free radicals in liver extract was devised. Throughout this method, the oxidized PPD produced by oxygen free radicals was determined colorimetrically. The increasing rate of PPD oxidation by liver homogenate was higher in tungstate fed animals than in standard diet fed ones. Among the fractionations of liver extract, the mitochondria1 and postmitochondrial fractions in the liver extract of tungstate fed animals led to a higher availability of PPD oxidation by PPD treatment compared with standard diet fed ones. In conclusion, these results suggest that an enhanced liver injury in tungstate fed animals treated with PPD may be due to oxygen free radicals produced in other systems except oxygen free radicals generating from cytosolic XO system. Especially, oxidative availability by PPD can be used for oxygen free radical detection in some tissue.

흰쥐에 사염화탄소 투여시 간 Xanthine Oxidase 활성에 미치는 Allopurinol의 영향

윤종국,이혜자,이상일 THE KOREAN SOCIETY FOR BIOMEDICAL LABORATORY SCINE 1995 Journal of biomedical laboratory sciences Vol.1 No.1

사염화탄소에의한 간손상시 CCl₄대사에 xanthine oxidase(XO)가 관련되는지를 규명하기 위한 일환으로 allopurinol을 흰쥐 체중 Kg당 50mg을 전처치한다음 CCl₄를 투여한후 처치하여 다음과 같은 결과를 얻었다. CCl₄투여로 인한 간조직의 postmitochondria 분획의 XO활성은 allopurinol을 전처치하므로서 현저히 감소되었으나 투석한 겨울에는 오히려 증가되었으며 type D로부터 type O로의 전환율은 감소되었다. 또한, 투석한 간조직의 XO를 반응속도적인 측면에서 관찰해볼 때 allopurinol을 전처치후 CCl₄투여군이 CCl₄단독투여군보다 Vmax가 크게 나타났다. CCl₄투여로 인한 체중당 간무게의 증가율과 혈청 alanine aminotransferase활성증가율은 allopurinol을 전처치하므로서 저하되었다. 한편 CCl₄투여로인한 간조직중 aniline hydroxylase 및 glucose 6 phosphatase활성감소율은 allopurinol을 전처치하므로서 저하되었다. 이상의 실험결과를 종합하여 볼 때 실험동물에 CCl₄와 allopurinol을 병행투여시 allopurinol이 사염화탄소에의한 간손상을 억제시키는 현상은 XO와 사염화탄소대사간에 관련성이 있음을 시사해주고 있다. To evaluate an effect of xanthine oxidase(XO) reaction system on the carbon tetrachloride(CCl₄) metabolism, CCl₄was given twice at O.1ml/10g body wt. at intervals of 18 hour to the mts and those pretreated with allopurinol (50mg/kg. body wt.). The influence of XO on the metabolism of CCl₄ was focused on the degree of liver damage and the activities of a CCl₄metabolizing marker enzyme, glucose-6-phosphatase. The increasing rate of liver weight per body weight and the levels of serum alanine aminotransferase to the control group were more decreased in allopurinol-pretreated rats than in those treated with CCl₄ alone. The liver XO activities were more increased in CC1₄-treated rats than the control group and the CC1₄-treated rats pretreated with allopurinol showed a decreased activities of XO compared to the CC1₄-treated rats. The type conversion (type D --> type O) rate was more decreased tendency in allopurinol pretreated rats than those treated CCl₄alone. In dialyzed liver enzyme preparations, all of the xanthine oxidase activities: CC1₄-treated, allopurinol and CC1₄-treated rats pretreated with allopurinol showed the more increased Vmax value than the control group, but similar Km value. Moreover, CC1₄-treated rats pretreated with allopurinol showed the more increased Vmax value than the group treated with CCl₄alone. In conclusion, it can not be negate the possibility of metabolism of CCl₄by the xanthine oxidase enzyme system.

흰쥐에 Xylene 반복 투여가 Xylene의 대사에 미치는 영향

전태원,이혜자,윤종국,이상일,조현국 THE KOREAN SOCIETY FOR BIOMEDICAL LABORATORY SCIEN 1999 Journal of biomedical laboratory sciences Vol.5 No.1

실험동물에 xylene의 반복 투여가 이물질의 대사에 어떠한 영향을 미치는지를 알아보기 위하여 흰쥐에 m-xylene과 olive oil의 동량혼합액을 체중 100g당 0.25ml씩 2일 간격으로 1, 4, 8, 12 및 16회 복강으로 투여한 다음 마지막 투여 24시간 후에 처치하여 다음과 같은 결과를 얻었다. 요 중 m-methylhippuric acid 함량은 m-xylene 4회 투여군의 경우 1회 투여군에 비하여 약 56%의 유의한 증가를 보였으며 이후 12회 투여까지 유사한 결과를 나타내었으나 m-xylene 16회 투여시에는 xylene 1회 투여군 치와 유사한 치로 감소되었다. 그리고 간조직의 microsomal aniline hydroxylase와 alcohol dehydrogenase 활성은 m-xylene 12회 투여시 까지는 대체적으로 점진적인 증가를 보였으나 이후 16회 투여시에는 12회 투여군에 비하여 유의한 감소를 보였다. 또한 aldehyde dehydrogenase 활성은 m-xylene 투여 회수에 비례해서 전 실험기간 동안 감소되었으며 특히 16회 투여군에서 본 효소활성의 현저한 감소를 보였다. 한편 본 실험조건에서 투여기간에 따른 진자현미경적 미세구조의 변화는 초기에 활면소포체의 증식이 보이다가 16회 투여군에서는 활면소포체가 감소되고 조면소포체가 증가되었다. 이상 실험결과는 흰쥐에 있어서 xylene 투여 회수에 따라서 요 중 m-methylhippuric acid의 농도 변동이 초래되며 이는 효소단백 유도에 따른 xylene 대사효소 활성 변동에 기인된 결과로 생각된다. To evaluate the effect of repeated treatment of xylene on its metabolism, m-xylene (0.25ml of 50% in olive oil/100 g body weight) has been intraperitoneally given to the rats 1, 4, 8, 12 and 16 times every other day. m-Xylene was once more administered to the animals after 24 hrs since last injection of it. And then the animals were sacrificed after 24 hrs. Four times xylene treated rats showed the significantly elevated urinary m-methylhippuric acid, compared to those treated with the singe dose of m-xylene with the continued similiar high levels of urinary m-methylhippuric acid up to the animals pretreated 12 times and then those treated 16 times defined the significantly decreased urinary m-methylhippuric acid compared to those treated 12 times. On the other hand, hepatic aniline hydroxylase and alcohol dehydrogenase activities demonstrated a gradual increase from the first group to the 12 times xylene-treated animals, but those treated 16 times showed the significantly decreased value compared with the 12 times treated-group. And aldehyde dehydrogenase activities in rats treated with m-xylene 8, 12 or 16 times were significantly decreased compared to those pretreated one or four times. In the early stage of xylene administration, proliferation of SERs were seen whereas SERs were decreased and RERs were clearly increased in xylene-treated rats 16 times. These results indicate that the frequency of xylene injection may influence upon the changes in xylene metabolite, m-methylhippuric acid and it may be due to induction of xylene metabolizing enzymes.

Cyclohexane에 의한 흰쥐의 폐독성

전태원,이상일,윤종국 대한의생명과학회 2000 Journal of biomedical laboratory sciences Vol.6 No.4

Cyclohexane에 의한 생체장기의 독성을 검토할 목적으로 휜쥐에 체중 kg당 1.56 g의cyclohexane을 복강으로 1일 1회 2일 간격으로 4회 투여한 다음 24시간 후에 처치하여 각 장기 (간,신장, 비장, 심장, 소장, 위 및 폐)의 체중 당 장기무게 (%)와 조직세포중 glucose-6-phosphatase (G6Pase) 활성변동을 측정한 결과, 실험군의 체중 당 폐무게가 대조군에 비하여 현저하게 증가 (p<0,001)하였고 이와는 반대로 G6pase 활성은 유의한 (p<0.001) 감소를 나타내었다. 그러나 폐를 제의한 장기에서는 별다른 차이를 볼 수 없었다. 이러한 결과는 cyclohexane이 주로 폐조직에 독작용을 야기시킨다는 것을 시사해 주고 있으며, 폐조직에서 malondialdehyde 함량이 대조군에 비하여 유의하게 (p<0.05) 증가된 것이 이를 뒷받침 해 주고 있다. 한편, cytochrome P450에 의해 나타나는 aniline hydroxylase활성은 폐조직이 간조직에 비하여 대단히 낮았으며, alcohol dehydrogenase (ADH) 활성 역시 간조직 보다 현저하게 낮게 나타났다. 그리고 cyclohexane투여로 인하여 ADH 활성은 간 및 폐조직 모두에서 증가하였으나 간조직에서 더욱민감한 반응을 나타내었다. 이상 실험결과를 종합해 볼 때, cyclohexane은 폐조직에 주로 독성을 나타 내며 이는 간조직에서 대사된 cyclohexane의 독성 중간대사산물인 cyclohexanone이 혈류를 통해 폐조직에 분포되어 나타난 결과로 사료된다. In order to search the target organ of cylclohexane toxicity, the rats were intraperitoneally treated with cyclohexane (1.56 g/kg of body wt.) four times every other day. In the increasing rate of organ weight per body weight (%) in cyclohexane-treated animals, the lung was highest among the liver, spleen small intestine, stomach, heart and kidney. And in the decreasing rate of glucose-6-phosphatase (G-6-Pase) activity in each organ that of lung was also highest among all organs. Lung MDA content was significantly increased (p<0.05) by the cyclohexane treatment. On the other hand, microsomal aniline hydroxylase activity in lung tissue both of control and cyclohexane-treated rats was greatly low as could be scarcely measured, but that in liver possessing high activity was significantly increased (p<0.05) in cyclohexane-treated rat compared with control. Alcohol dehydrogenase activity in lung was markedly higher than that of liver and the latter was significantly (p<0.05) increased by the cyclohexane treatment. In conclusion, cyclohexane treatment to the rats showed mainly lung toxicity and it may be responsible far cyclohexanon, cyclohexane metabolite, distributed from liver.

자궁경부의 선암종에서 Polymerase Chain Reaction에 의한 Human Papillomavirus DNA 16/18의 검색

이상숙,박남조,윤종국 대한병리학회 1995 Journal of Pathology and Translational Medicine Vol.29 No.4