27. 담도결찰 흰쥐에서 간내 microsomal enzyme 활성의 변화

박은전(Eun Jeon Park),김지영(Ji Young Kim),고건일(Geon Il Ko),김재백(Jae Baek Kim),손동환(Dong Hwan Sohn) 한국약제학회 1996 한국약제학회 총회 및 학술대회 요지집 Vol.- No.26

N/A

회원 학술보고 : 포스터 발표 / 33. 실험적 간경화 모델에서 Theophylline 의 Biotransformation (2)

박은전(Eun Jeon Park),손동환(Dong Hwan Sohn),김재백(Jae Baek Kim) 한국약제학회 1994 한국약제학회 총회 및 학술대회 요지집 Vol.- No.24

실험적 간경화 동물모델 비교

박은전(Eun Jeon Park),김재백(Jae Baek Kim),손동환(Dong Hwan Sohn),고건일(Geon Il Ko) 대한약학회 1997 약학회지 Vol.41 No.5

Hepatic cirrhosis is a common response to chronic liver injury from many causes and is one of the most common cause of all deaths. This study was carried out to compare experimental hepatic cirrhosis in rats to understand this disease and to apply for the pharmacokinetics in disease state. Following three kinds of experimental models were induced; 1) Bile duct ligation/scission (BDL/S), 2) N, N-dimethylnitrosamine(DMN), 3) Carbon tetrachloride. The hepatic cirrhosis was characterized by examing the liver/body weight ratio, serum biochemical values, hydroxyproline content in liver and histopathological lesions in cirrhotic rat liver. The results are as follows : (1) In BDL/S, the liver was enlarged to 250% of normal liver. In contrast the liver was shrinked to 48% and 78% of the normal liver in DMN and carbon tetrachloride, respectively. (2) In carbon tetrachloride and BDL/S, the serum ALT, AST, ALP and total bilirubin levels were significantly increased to 200~300% of normal level, while ALT and total bilirubin levels were significantly increased in DMN group. (3) Hydroxyproline content in cirrhotic rat liver was significantly 200~500% higher than that of normal liver. (4) Nodular formation with fibrosis was observed in BDL/S, DMN, carbon tetrachloride induced cirrhotic rat liver.

영지로부터 추출한 다당체의 실험적 간경화에 대한 섬유화 억제효과

박은전(Eun Jeon Park),김기영(Ki Young Kim),김재백(Jae Baek Kim),김수웅(Soo Woong Kim),이승용(Seung Yong Lee),손동환(Dong Hwan Sohn) 대한약학회 1994 약학회지 Vol.38 No.3

This study was carried out to investigate the antifibrotic effects of polysaccharides extracted from Garnoderma lucidum. The biliary cirrhosis was induced by bile duct ligation/scission(BDL/S) in rats. BDL/S rats were dosed 5 mg/rat/day orally for 4 weeks after the operation. Antifibrotic effects were evaluated by serum biochemical values, serum procollagen type III peptide(PIIINP) levels, liver hydroxyproline contents, and light microscopical histology. The results obtained were as follows; 1) PIIINP levels in sera of treated BDL/S group were lowered to 50% of those of untreated BDL/S group. 2) Hydroxyproline contents in the liver of treated BDL/S group were also reduced to 83% of those of untreated BDL/S rats. 3) The hepatic damage such as hepatocellular necrosis, inflammation, bile duct proliferation and fibrosis was less severe in the livers of treated rats. These results suggest polysaccharides extracted from Garnoderma lucidum to be a promising agent for the inhibition of hepatic cirrhosis(fibrosis).

담도결찰 흰쥐에서 영지배양 균사체 유래 다당체의 항섬유화 효과 검색 및 용량의존성시험

박은전(Eun Jeon Park),고건일(Geon Il Ko),김재백(Jae Baek Kim),손동환(Dong Hwan Sohn) 대한약학회 1997 약학회지 Vol.41 No.2

This study was carried out to investigate the dose dependent antifibrotic effects of polysaccharide from mycelium of Ganoderma lucidum. The experimental hepatic cirrhosis was induced by bile duct ligation/scission (BDL/S) in rats. BDL/S rats in each group were dosed 0.5 mg, 2.0 mg, 5.0 mg or 10.O mg/rat/day orally for 4 weeks after the operation. Antifibrotic effects were evaluated by serum biochemical values, hydroxyproline contents, and light microscopical histology. The results obtained were as follows: 1) Hydroxyproline contents in liver of 5.0 and 10.0mg polysaccharide-treated BDL/S rats were significantly reduced 2) In serum test, ALT, AST, ALP values in polysaccharide from Ganoderma lucidum-treated group were lower than BDL/S control group 3) The hepatic damage such as hepatocellular necrosis, inflammation, bile duct proliferation and fibrosis was less severe in the livers of 2.0 mg and 5.0 mg polysaccharide-treated rats. These results suggest that polysaccharide from mycelium of Ganoderma lucidum to be a promising agent for the inhibition of hepatic cirrhosis.

도인 추출물의 간보호 및 항섬유화 효과

남극성,박은전,손동환,고건일,Na Ji-Xing,Park Eun-Jeon,Sohn Dong-Hwan,Ko Geon-Il 대한한의학방제학회 2004 大韓韓醫學方劑學會誌 Vol.12 No.2

This study was carried out to investigate the liver protective effects of extracts from Persicae Semen (WT-003, WT-005, WT-006). The acute hepatic injury was induced by intraperitoneal injection of alpha-naphtylisothiocyanate (75 mg/kg, p.o.) and treated with WT-006 (100 mg/kg/day, 200 mg/kg/day, 400 mg/kg/day). The experimental hepatic fibrosis was induced by bile duct ligation/scission(BDL/S), duration of 4 weeks and treated with WT-003, WT-005 or WT-006 (200 mg/kg/days for 4 week). In acute liver injury, WT-006 (200 or 400 mg/kg) lowered serum alanine transferase(ALT) and aspartate transferase(AST) significantly. In fibrotic rats, WT-006 treatment inhibited the hydroxyproline deposition in liver and lowered serum AST, ALT and ALP, significantly. These results suggest WT-006 extract, which does not contain amygdalin, from Persicae Semen have liver protective and antifibrotic effects in rats.

리포폴리사카라이드와 갈락토사민의 투여로 인한 생쥐 치사율에 미치는 글리시라진의 억제효과

오창욱(Chang Wook Oh),송경(Kyung Song),박은전(Eun Jeon Park),손동환(Dong Hwan Sohn),김재백(Jae Baek Kim),고건일(Geon Il Ko) 대한약학회 1996 약학회지 Vol.40 No.1

This study was done to investigate the effect of glycyrrhizin on the lethality induced by galactosamine and lipopolysaccharide coadministration in mice. Glycyrrhizin was injected intravenously as a multiple dose at 20, 15, 10, 5, and O hr before galactosamine and lipopolysaccharide coadministration. Lethality and tumor necrosis factor (TNFalpha) level in serum were surveyed as markers of glycyrrhizin effect. Glycyrrhizin had no effect on the lethality induced by galactosamine and lipopolysaccharide when glycyrrhizin was administered as a single dose. Glycyrrhizin reduced the lethality induced by galactosamine and LPS in dose-dependent manner when glycyrrhizin was administered as a multiple dose at 20, 15, 10, 5 and O hr before galactosamine and lipopolysaccharide coadministration. Glycyrrhizin reduced the serum TNFalpha level.

Cyclosporin 함유제제의 생물학적 동등성 시험

박은전,손영택,손동환,고건일,김재백 圓光大學校 藥品硏究所 1995 藥品硏究所報 Vol.10 No.1

실험실적 간질환에 있어서 P450 2El의 Molecular Regulation

박선미,박은전,고건일,손동환 圓光大學校 藥品硏究所 1993 藥品硏究所報 Vol.8 No.1

Cytochrome P450 2El is involved in the metabolic activation of many xenobliotics involved with human toxicity. The molecular mechanism of cytochrome P450 2El reduction in acute CCl_4 treatment and cirrhosis models were examined by measuring its enzymi activity, immunoreactive protein contents, and mRNA levels. Ⅰ. Acute CCl_4 treatment Aniline hydroxylase and the amounts of immunoreactive P450 2El were rapidly decreased in 24-48h and recovered in 72-96h after a single dose of CCl_4. The activities of pentoxyreasorufin-0-dealkylase and ethoxyresorufin-0-deethylase were also suppressed in 24h and begun to repair in 48h. The decline in the P450 1A content correspond to the inhibition pattern of P450 1A enzyme acitivity. However the decrease in immunoreactive P450 2C content wasn't observed. The decreases in P450 2El enzyme activity and immunoreactive protein by acute CCl_4 treatment were accompanied by a decline in its mRNA levels. The data thus suggested a pre-translational reduction of P450 2El by acute CCl_4 treatment probably due to destruction of the P450 2El gene by its own substrate. Ⅱ. Cirrhosis models In CCLl_4-induced cirrhosis, aniline hydroxylase, pentoxyreaorufin-0-dealkylase, and ethoxyresorufin-0-deethylase were suppressed and the amounts of immunoreactive P450 2El, and P450 1A were rapidly decreased. In contrast, the changes or reduction in the immunoreactive amounts of P450 2C was not so apparent as the inhibition of the corresponding catalytic activity. In bile duct ligation/scission(BDL)-induced cirrhosis, aniline hydroxylase and pentoxyresorufin-0-dealkylase were decreased, but ethobyresorufin-0-deethylase wasn't changed. No change were observed in the amounts of immunoreactive P450 2El, P450 2C, and P450 1A. In dimethylnitrosamine(DMN)-induced cirrhosis, only pentoxyresorufin-0-dealkylase was decreased and aniline hydroxylase and ethoxyresorufin-0-deethylase weren't suppressed. No change were observed in the amounts of immunoreactive P450 2El, P450 2C, and P450 1A. The decreases in P450 2El enzyme activity and immunoreactive protein by CCl_4-induced cirrhosis were accompanied by a decline in its mRNA levels. The data thus suggested a pre-translational reduction of P450 2El by CCl_4-induced cirrhosis probably due to destruction of the P450 2El gene by its own substrate.

실험적 간질환에서 Theophylline의 체내동태

박은전,김재백,고건일,손동환 圓光大學校 藥品硏究所 1994 藥品硏究所報 Vol.9 No.1

This study was carried out to investigate the mechanism of altered drug elimination in hepatic diseases using theophylline as an example of a drug that is extensively metabolized by the liver and have a narrow therapeutic range. Firstly, we established the experimental hepatic cirrhosis model in rats. Three kinds of method were used to induce hepatic cirrhosis; (1) bile duct ligation/scission; (2) N, N- dimethylnitrosamine; (3) carbon tetrachloride. Secondly, the pharmacokinetics of theophyl1ine(8㎎/㎏, as theophyl1ine, i.v.) was studied in three kinds of experimental hepatic cirrhosis model. And the concentration of 1,3-dimethyluric acid (major metabolite of theophylline) in plasma of the cirrhotic rats was determined. Thirdly, the activities of the hepatic microsomal aniline hydroxylase and ethoxyresorufin-O-deethylase were determined. And as an in vitro test, theophylline metabolites were determined from the extract from the incubation mixture of the theophylline and hepatic microsomal system. The hepatic enzyme activity was correlated with the content of the metabolites formed after the incubation. The results were as follows; 1) The serum ALT, AST, ALP, total bilirubin levels and hydroxyproline content in liver of the experimental hepatic cirrhosis model were significantly elevated and the histological aspects of the liver appeared as cirrhosis. 2) In the experimental hepatic cirrhosis, the values of AUC and t_½ were significantly increased and the Cl_8 and K_10 was significantly reduced. The 1,3-dimethyluric acid was not detected in cirrhotic rats. 3) In microsomal incubation, 1,3-dimethyluric acid formation was decreased in cirrhotic rats. And the decrease in 1,3-dimethyluric acid formation in vitro was accompanied by the decline in aniline hydroxylase(P450 2E1 related) activity in experimental hepatic cirrhosis. The results indicate that in experimental hepatic cirrhosis, altered theophylline elimination is mainly due to decreased hepatic drug metabolizing activity and the biotransformation of theophylline to 1,3-dimethyluric acid may be affected by cytochrome P4502E1 .