흰쥐 膽汁鬱滯 肝臟의 5'-Nucleotidase와 Gamma-Glutamyl Transpeptidase의 活性値

郭春植,張億奎 啓明大學校 醫科大學 1985 계명의대학술지 Vol.4 No.1

膽汁鬱滯가 隨伴되는 肝膽道 疾患에서 增加되는 血淸 5'-NT와 GGT의 增加 機轉을 仔細히 알아보기 爲하여 흰쥐의 總輪膽管 또는 中葉과 左側外葉 膽管을 結紮하고 經時的으로 血淸과 肝組織의 5'-NT, GGT 및 ALP의 變動을 觀察하는 한편 肝組織 損傷과 肝 및 血淸蛋白 合成能 等을 測定하였으며 아울러 이들 酵素와 肝 및 血淸蛋白 合成能에 對한 actinomycin D의 影響도 觀察하여 相互比較하였다. 總輪膽管을 結紮한 흰쥐에서는 血淸 總 bilirubin이 12時間에 顯著히 上昇되어 6日까지 繼續 높은 濃度를 維持하였다. 이와같이 膽汁鬱滯가 持續되는 狀態에서 血淸과 肝組織의 膜結合 및 可溶性 5'-NT, GGT와 ALP는 顯著히 上昇되었다. 그러나 이들 血淸 酵素와 肝組織 酵素間에는 그 上昇 時期와 上昇率이 큰 差異를 보였다. 즉 血淸 5'-NT와 GGT는 總輪膽管 結紮後 12時間에 急激히 上昇됨에 比해 肝組織의 膜結合 및 可溶性 5'-NT와 GGT는 2日째에 顯著히 上昇되었다. 그리고 그 上昇率은 前者가 後者에 比해 훨씬 높았다. 한편 血淸肝性 ALP와 肝組織의 膜結合 및 可溶性 ALP는 모두 12時間에 急激히 增加되었으며 그 上昇率은 역시 前者가 높았다. Actinomycin D를 總輪膽管 結紮 前後에 投與하고 1日後 이들 酵少의 變動을 關察했을 때 血淸 ALP나 肝組織의 膜結合 ALP는 다같이 懸著히 그 活性이 抑制되었다. 그리고 血淸 및 肝組織의 膜結合 GGT와 肝組織의 膜結合 5'-NT는 actinomycin D 投與後 1日에는 意義있는 抑制 現象을 보이지 않았다. 그러나 1.5日 後에는 肝組織의 膜結合 5'-NT와 GGT는 意義있는 抑制 現象을 나타내었다. 이와는 反面에 血淸 5'-NT는 actinomycin D를 投與하지 않은 總輪膽管 結察群보다 약 75%의 增加를 보였다. 總輪膽管 結紮로서 血淸의 ALP, AST 및 LDH는 다같이 12時間부터 顯著히 增加되어 1日에는 最固値에 達하고 以後 減少되기는 하나 繼續 높은 値를 維持하였다. 그리고 그 增加率의 크기는 血淸 ALP, AST, LDH의 順序였다. 그러나 部分膽管을 結紮한 흰쥐에서는 이들 酵素가 前者에 比해 經度의 增加에 不過하였다. 總輪膽管을 結紮했을 때 肝組織의 總 ALP, 總 AST 및 LDH는 5'-NT, GGT 및 ALP와는 달리 오히려 總輪膽管 結紮後 1日 또는 2日後부터 減少되어 繼續 減少된 値를 보였다. 그리고 역시 部分膽管 結紮群에서도 膽道가 閉鎖된 肝葉이 減少된 値를 나타내었으며 그 減少率은 總輪膽管 結紮群보다 낮았다. 한편 部分膽管을 結紮한 흰쥐에서는 血淸 bilirubin의 增加가 없음에도 血淸 5'-NT, GGT 그리고 血淸肝性 ALP는 모두 實驗 全期間동안 增加되었다. 그러나 그 增加의 程度는 總輪膽管을 結紮한 흰쥐보다는 낮았다. 또한 肝組織中의 膜結合 5'-NT, GGT 및 ALP는 같은 흰쥐에서 다같이 膽道가 閉鎖된 肝葉이 膽道가 開放된 肝葉보다 增加되었으며 이것도 역시 總輪膽管을 結紮한 群보다는 낮은 增加率을 보였다. 그리고 肝組織의 可溶性 5'-NT와 GGT는 實驗全期間동안 變動을 보이지 않았다. 그러나 肝組織의 可溶性 ALP는 膽道가 閉鎖된 肝葉이 開放된 肝葉보다 훨씬 높았다. 總輪膽管을 結紮한 흰쥐에서 amino acid mixture-(U)-C의 肝組織 및 血淸蛋白에의 編入速度는 酵素들의 活性 增加보다는 약간 늦게 兩者 모두 總輪膽管 結紮後 1日부터 增加되기 始作하여 6日까지 繼續 높은値를 維持하였다. 한편 部分膽管을 結紮한 動物에서도 역시 膽道가 閉鎖된 肝葉이 膽道가 開放된 肝葉보다 amino acid mixture-(U)-C의 肝蛋白에의 編入率이 增加되었으나 그 增加率은 總輪膽管을 結紮한 흰쥐보다는 낮았다. 그러나 이의 淸血蛋白에의 編入率은 意義있는 增加를 보이지 않았다. 그리고 總輪膽管 結紮 前後에 actinomycin D를 投與했을 때 肝과 血淸蛋白 合成이 顯著히 抑制되었다. 總輪膽管을 結紮한 흰쥐에서 肝은 總輪膽管 結紮後 2日에 약 1.6倍 6日은 약 2.7倍의 腫大를 보였다. 그러나 部分膽管 結紮群에서는 肝臟의 腫大의 程度가 經度에 不過하였다. 그리고 總輪膽管 結紮群이나 部分膽管結紮群 모두 肝組織의 總蛋白 濃度는 別 變動이 없었다. 그러나 可溶性 蛋白의 濃度는 6日에 意義있는 減少를 보였다. 以上의 成績으로 보아 膽汁鬱滯時 惹起되는 血淸 5'-NT 및 GGT의 增加는 肝細胞膜의 生化學的 變性에 依해서 細胞膜에 含存되어 있는 이들 酵素가 血中으로 多量 遊離되어 나오는데 起因할 것으로 생각되며 同時에 膽道細胞의 增殖과 이 細胞에서의 이들 酵素의 合性 亢進이 더욱 甚한 血中增加를 誘導하는 것으로 생각된다. 그리고 어떤 物質에 誘導因子인지는 分明치 않으나 혹 膽汁鬱滯로 因한 膽汁酸의 增加가 이들 酵素合成을 誘導하는 것이 아닌가 생각된다. Changes in the activities of 5'-nucleotidase, gamma-gultamyl transpetidase, and alkaline phosphatase in serum were studied with rats which had bile duct ligated totally and partially over a period of 6 days after operation. The above enzymes were also observed in the activities of both membrane bound and soluble of liver. Activities of alanine aminotransferase, asparate aminotransferase, and lactate dehydrogenase in both serum andliver, and incorporation rates of amino acid mixture-(U)-?? into both serum protein and liver protein were compared with the changes obwerved above. And then the effects of actinomycin D adminstered to totally ligated rats were also observed. The levels of total bilirubin of serum increased sharply after the ligation of the common bile duct. 5'-Nucletidase, gamma-glutamyl transpeptidase and alkaline phosphatase showed increased activities both in membrane bound and in soluble of liver, however, the increases of 5'-nucleotidase and gamma-glutamyl transpeptidase were not detectable until second day, whereas the significant increase of alkaline phosphatase was detectable within 12 hours after common bile duct ligation. In the serum, however, the activities of these enzymes were significantly elevated in 12 hours after operation. Maximum levels were appeared on first day for 5'-nucleotidase and on third day for alkaline phophatase and gamma-glutamyl transpeptidase. 5'-Nucleotidase activities in the serum of both control rats and totally bile duct ligated ones were forund to be approximately increased by 1.7 fold 1 day after the administration of actinomycin D. The activities of hepatic membrane bound and serum hepatic alkaline phosphatase were significantly diminished 1 day after the administration of actinomycin D. The activities of hepatic membrane bound and soluble of both 5'-nucleotidase and gamma-glutamyl transpeptidase, and serum gamma-glutamyl transpeptidase did not change 1 day after the adminstration of actinomycin D. But the activies of hepatic membrand bound of both 5'-nucleotidase and gamma-glutamyl transpeptidase were significantly inhbited 1.5 day after the administration of actinomycin D. Partial ligation of bile duct which is the ligation of bile ducts of both median and left lateral lobes, also induced a significant increase of 5'-nucleotidase, gamma-glutamyl transpeptidase, and alkaline phosphatase in serum but serum bilirubin level remained within the normal range. Liver membrane bound of 5'nucleotidase and gamma-glutamyl transpeptidase also showed a marked increase but liver soluble of those did not change. Alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase of serum were strikingly increased after total ligation of bile duct, but they were increased moderately in partially ligated rats. And the activities of the three enzymes were markedly decreased in the liver of totally and partially bile ducts ligated rats. Incorporation rates of amino acid mixture-(U)-?? into both serum protein and liver protein showed a significant increase after the total bile duct ligation in rats and reverse effect was observed after the administration of a actinomycin D. In the case of partial ligation, the incorporation rate showed a slight increase in ligated lobe compared with patent lobe of liver. The above results showed that bile duct ligation might cause an early increase in synthesis of he[atic alkaline phosphatase, however, the increase in synthesis of 5'-nucleotidase and gamma-glutamyl transpepetidase is delayed until the phase of bile duct proliferation. The earyl changes within 1 day in serum activities of 5'-nucleotidase and gamma-glutamyl transpeptidase seemed to be caused by alteration of membrane permeability of hepatic cell.

Saponin 含有 生藥이 肝 Xanthine Oxidase 活性에 미치는 影響

張億奎,李相日,朴種珉,鄭丁錄,許瑾 영남대학교 자원문제연구소 1985 資源問題硏究 Vol.4 No.-

The present study was undertaken to elucidate the effect of butanol fraction which were extracted from various oriental medicine, on the hepatic xanthine oxidase activity in vitro. The results were as follow. The butanol fraction of gypsophyla, platicodi and clover did not affect the hepatic xanth-ine oxidase activity, unlike sodium dodecylsulfate which is an action of artificial detergent. The hepatic xanthine oxidase activity was decreased by the butanol fraction of garlic, sly-cyrrhizae and polygalae, particularly glycyrrhizae and polygalae butanol fraction strongly inhibited the hepatic xanthine oxidase activity. When ginseng saponin was added, the xanthine oxidase activity was enhanced in a small dose, whereas in a large dose, it showed the inhibitory effect like sodium dodecylsulfate.

藥用Sulfonamide 類의 Schiff 監基의 合成과 抗菌作用

金鍾潤,張億奎,田應鎬 嶺南大學校府設 基礎科學硏究所 1983 基礎科學硏究 Vol.3 No.-

Twelve new Schiff bases were synthesized by condensation of two kinds of medicinal sulfonamides with eight kinds of aromatic aldehydes. They were identified by means of the elemental analysis, and UV and IR spectrochemical analyses. Antibacterial activity of the Schiff bases was tested in vitro against one gram-positive and seven gramnegative bacterial species. The results show that some of the compounds are more effcetive than each of corresponding sulfonamides against gram-positive St. aureus, exerting more remarkable activity compared to that against the gram-negative species. Therefore, the mechanism of action of the Schiff bases seems to be different from that of medicinal sulfonamides.

총수담관을 결찰한 흰쥐의 혈청 ( Ceruloplasmin 에 대한 actinomycin D 의 효과

곽춘식,장억규 ( Chun Sik Kwak,Uk Kyu Chang ) 생화학분자생물학회 1979 BMB Reports Vol.12 No.2

This study was intended to observe the changes in serum ceruloplasmin concentration after the ligation of common bile duct in rats. Several values of liver function tests are compared with the changes observed. Then the effects of actinomycin D administered rats, treated in the same method, were also observed for comparison. Common bile duct ligation in the rats brought about a rapid increase in serum ceruloplasmin concentration. Serum ceruloplasmin show ed an increase: of 2, 2. 5 and 3 fold at the 2nd, 3rd and 6th day respectively following the bile duct ligation. But the increase was observed markedly inhibited in the case of administration of actinomycin D (50㎍/1008 of body weight) one hour prior to and eighteen hours after the ligation of the common bile duct in rats. After the ligation of common bile duct, the levels of serum alkaline phosphatase increased rapidly. This continued to be high throughout the experiments. The increase of serum alkaline phosphatase was significantly diminished with additional actinomycin D treatment. Serum glutamic pyruvic transaminase increased strikingly after ligation of common bile duct but the increase was not so obvious when adminstered with actinomycin D. The levels of serum total bilirubin increased sharply after the tigation of the common bile duct. The above results suggest that the bile duct ligation may cause the induction of serum ceruloplsmin and this is assumed due to the increase of the apoceruloplasmin biosynthesis.

총수담관을 결찰한 흰쥐의 혈청 Ceruloplasmin에 대한 Actinomycin D의 효과

곽춘식,장억규,Kwak, Chun-Sik,Chang, Uk-Kyu 생화학분자생물학회 1979 한국생화학회지 Vol.12 No.2

담즙물체시에 증가되는 혈청 Ceruloplasmin의 증가기전을 알아보기 위하여 흰쥐의 총수담관을 결찰하고 경시적으로 혈청 Ceruloplasmin의 농도를 측정하는 한편 간의 담즙배설장애, 간세포손상 등을 관찰하였으며 아울러 이들에 대한 actinomycin D의 영향도 관찰하여 상호 비교하였다. 혈청 ceruloplasmin 은 총수담관결찰로 그 농도가 수술후 6시간부터 증가하여 24시간에는 약 1배, 2일에는 약 2배, 3일에는 약 2.5배 그리고 6일에는 약 3배로 증가되었다. 그러나 이 효소농도의 증가는 actinomycin D를 수술전후 투여함으로써 저해되어 정상치 수준으로 저하되었다. 총수담관 결찰로써 혈청의 alkaline phosphatase와 glutamic pyruvic transaminase도 그 활성이 다같이 현저히 증가되었으나 혈청 ceruloplasmin의 증가와는 시기적으로 상이하였다. 그리고 이들 역시 actinomycin D에 의해서 그 활성이 억제되었으나 그 억제의 정도는 혈청 ceruloplasmin에 비하여 덜 현저하였으며 이들 중 혈청 glutamic pyruvic transaminase가 가장 적은 억제율을 보였다. 그리고 혈청의 총 bilirubin은 총수담관결찰로써 현저히 증가되었다. 이상의 성적으로 보아 담즙물체시 혈청 ceruloplasmin의 농도증가는 어떤 물질에 의해 유도되는지는 알 수 없으나 간장내에서 apoceruloplasmin의 계속적인 생성증가가 그 원인일 것으로 생각된다. This study was intended to observe the changes in serum ceruloplasmin concentration after the ligation of common bile duct in rats. Several values of liver function tests are compared with the changes observed. Then the effects of actinomycin D administered rats, treated in the same method, were also observed for comparison. Common bile duct ligation in the rats brought about a rapid increase in serum ceruloplasmin concentration. Serum ceruloplasmin show ed an increase: of 2, 2.5 and 3 fold at the 2nd, 3rd and 6th day respectively following the bile duct ligation. But the increase was observed markedly inhibited in the case of administration of actinomycin D ($50{\mu}g/100g$ of body weight) one hour prior to and eighteen hours after the ligation of the common bile duct in rats. After the ligation of common bile duct, the levels of serum alkaline phosphatase increased rapidly. This continued to be high throughout the experiments. The increase of serum alkaline phosphatase was significantly diminished with additional actinomycin D treatment. Serum glutamic pyruvic transaminase increased strikingly after ligation of common bile duct but the increase was not so obvious when adminstered with actinomycin D. The levels of serum total bilirubin increased sharply after the tigation of the common bile duct. The above results suggest that the bile duct ligation may cause the induction of serum ceruloplsmin and this is assumed due to the increase of the apoceruloplasmin biosynthesis.

마늘 成分이 肝 Aldehyde Oxidase 活性에 미치는 影響

金永文,許瑾,張億奎 영남대학교 자원문제연구소 1986 資源問題硏究 Vol.5 No.-

It was attempted to observe the effect of garlic on the hepatic aldehyde oxidase activity in this study. Aldehyde oxidase (EC 1.2.3.1.) are thought to play a physiological role in the metabolism of heterocyclic compounds and various drugs including endogenous and exogenous compounds. The activity of aldehyde oxidase in mouse liver was decreased by the treatment of garlic juice. Furthermore, inhibition of enzyme activity was slightly greater in boiled garlic juice than fresh garlic juice treated group. Allicin, heat-treated allicin fraction and saponin fraction markedly inhibited purified rabbit liver aldehyde oxidase activity in vitro. The decreasing effect was greater heat-treated allicin than allicin fraction. These observation led to conclude that the garlic components which are stable substance in heat may regulate the hepatic aldehyde oxidase activity. 05 The effect of water extract of Siegesbeckiae Herba on the drug induced hepatic damage was investigated in this study. Histopathologic changes of liver were also examined in rats fed with Siegesbeckiae Herba extract. The liver damage was induced by intraperitoneal injection of CCI4 (0.1m1/100g) 1) Compared with the nontreatment and posttreatment group, the pretreatment group showed a remarkable decrease in increase of liver and spleen weight after acute liver damage. 2) Increase of serum AST and ALT activities, and hepatic lipid peroxidation value induced by hepatic damage in rats was inhibited by pretreatment of Siegesbeckiae extract. 3) Histological changes of liver induced by CCI4 injection were significantly reduced by Siegesbeckiae pretreatment. These results suggest that water extract of Siegesbeckiae Herba may protect the liver from CCl4 toxicity.

數種의 Thiocarbohydrazone類의 合成과 抗菌作用

申容禎,최보길,張億奎,金鍾潤 영남대학교 자원문제연구소 1985 資源問題硏究 Vol.4 No.-

Seven new compounds were synthesized as potential effective antibacterial agents, three of them and the others being mono- and dithiocarbohydrazones, respectively. The compounds were identified by means of the elemental analysis, and electronic and IR spectrophotometry. They were tested for antibacterial activity in vitro against a grant-positive and seven gram-negative species. The data showed that, regardless of the type of the thiosarbohydrazones, the compounds in which one aldehyde moiety is 2-(5-nitro) furfural or 2-(5-nitro) furylacrolein exerted powerful antibacterial activity against gram-positive Staphylococcus aureus, while showing the weak activity, on the whole, against the gram-negative species.

亞窒酸鹽과 acetaminophen과의 反應 및 反應生成物의 突然變異原性 硏究

鄭圭燦,男景琇,張億圭 영남대학교 자원문제연구소 1984 資源問題硏究 Vol.3 No.-

Much attention has been paid to environmental mutagens as possible causes of human cancers. Industrial chemicals, drugs, cosmetics. pesticides and food additives have been the subjects of intensive studies. Particularly, it is well known that substances which have secondary or tertiary amino group in their structure are so easily reacted with nitrite, make N-nitroso compounds that induce human cancer Up to now, a large number of N-nitroso compounds were synthesized and their toxicological properties (i. e., mutagenicity, carcinogenicity) were identified by Ames test which used typhimurium . We have tested acetaminophen that is increasingly used as a analgesic and antipyretic drug. Acetaminophen easily reacted with nitrite at acidic conditions, reaction product was purified and mutagenicity of reaction product %as tested by Ames method.

Sodium Nitrite와 L-Arginine과의 反應 및 反應生成物의 突然變異原性에 關한 硏究

鄭圭燦,鄭光元,張億奎 영남대학교 자원문제연구소 1985 資源問題硏究 Vol.4 No.-

Nitrates and nitrites are used as preservatives and coloring agents in food products, especially cured meats. A number of materials including secondary or tertiary amines or amides in their structure may interact with nitrite to form N-nitroso compounds which are known as chemical carcinogen or Mutagen. Food, drugs, cosmetics, agricultural chemicals (e. g., pesticides), tobacco and certain occupational settings are significant sources of nitrosatable amides and amines, Amino compounds that may interact with nitrite to form N-nitroso compounds are present in the environment. In this study, we have tested L-Arginine, one of the amino acids. L-Arginine was reacted with nitrite at acidic conditions and reaction products were purified and analyzed by means of Thin-Layer Chromatograpy, Infrared Absorption Spectroscopy and Nuclear Magnetic Reso-nance Spectroscopy. Studies about it's mutagenicity, DNA damage were tested by "Rec-assay".

唾液에서 分離한 Streptococcus mutans에 의한 窒酸鹽의 還元 및 Dimethylnitrosamine의 生成에 관한 연구

鄭圭燦,金成煥,南景琇,張億奎,金亨秀 영남대학교 자원문제연구소 1986 資源問題硏究 Vol.5 No.-

It is widely known that carcinogenic N-nitroso compounds are formed through the reaction of nitrite with secondary and tertiary amines in vitro and in vivo under acidic conditions. In human saliva, nitrite is a possible precursor of N-nitroso compound even at neutral pH and nitrate is reduced to nitrite by nitrate reducing bacteria in oral cavity at dorsum linguae. We have tested the concentration of nitrite and nitrate in human saliva and the degrees of nitrate reduction by oral microflora and some bacteria (St. mutans, St. uberis) which were able to reduce nitrate were separated from human saliva and lastly in vitro formation of dimethylnitrosamine (DMNA) by St. mutans separated from human saliva. Nitrate concentration was higher than nitrite in human saliva and nitrate reducing activity of human saliva was about 23.5%. Main nitrate reducing bacteria were identified as St. uberis and St. mutans which were presented in large quantities. In vitro, N-dimethylnitrosamine was formed by the reaction between dimethylamine and nitrite in the presence of St.mutans.