흰쥐 관류간 모델에서 저산소 및 산소재도입시 vitamin C 가 간장기능에 미치는 영향

고준일(Jun Il Ko),조태순(Tai Soon Cho),이선미(Sun Mee Lee) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.1

This study was done to investigate the effect of vitamin C on hypoxia/reoxygenation-induced hepatic injury in isolated perfused rat liver. Isolated livers from rats fasted 18 hours were subjected to 45 min of hypoxia followed by reoxygenation for 45 min. The perfusion medium used was Krebs-Henseleit bicarbonate buffer (pH 7.4) and 0.5 mmol/L of vitamin C was added to the perfusate. Alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were significantly increased by hypoxia/reoxygenation. These increases were augmented by vitamin C. Glucose output and bile flow were markedly decreased by hypoxia/reoxygenation. Vitamin C aggravated the decrease of glucose output but had little effect on bile flow. Our findings suggest that hypoxia/reoxygenation diminishes hepatic metabolic and secretory functions, and vitamin C significantly aggravates these changes.

새로운 플라보노이드 유도체인 DA-6034의 TNBS 유발성 염증성대장염 모델에서의 치료효과

손미원(Mi Won Son),고준일(Jun Il Ko),김희기(Hee Kee kim),장동경(Dong Kyung Jang),유무희(Moo Hi You),김원배(Won Bae Kim),이강춘(Kang Chun Lee),송인성(In Sung Song) 대한약학회 1998 약학회지 Vol.42 No.2

The efficacy of DA-6034, a new flavonoid derivative, was investigated in comparison with sulfasalazine in a trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. Under light anaesthesia with ether, rats were subjected to intracolonic administration of 30mg TNBS in 50% ethanol (0.5ml) and were then sacrificed at 7 or 21 days after colitis induction. The TNBS control group (the saline treated colitic rat) exhibited ulceration and inflammation of the distal colon with formation of granuloma and pathologic connections. Moreover, an increase in colonic myeloperoxidase (MPO) activity (investigated as an index of leukocyte adhesion and accumulation) and an elevated colonic leukotriene B4 (LTB4) level were observed. The colitic rats received DA6034 (0.3-30mg/kg) or sulfasalazine (50-100mg/kg), prednisolone (0.3-3mg/kg) after the induction of colitis until they were sacrificed. Oral treatment with DA-6034 resulted in significant reductions of macroscopic colonic damage, colonic inflammation. DA6034 had a more potent effect than sulfasalazine and prednisolone on macroscopic colonic damage, while it has similar effect with prednisolone on the reduction of colonic LTB4 synthesis and MPO activity. This study show, therefore, that DA-6034 is effective m attenuating the colonic lesion in an TNBS-induced colitis model. Furthermore, the results suggest that the effect of DA-6034 is partially related to its action on LTB4 synthesis and MPO inhibition.

마우스에서 VEGF 발현 Naked DNA 벡터인 pCK-VEGF의 약동력학 및 조직내 분포

도현미(Hyounmie Doh),고준일(Jun-IL Ko),이종진(Jong-Jin Lee),손미원(Miwon Son),조홍찬(Hongchan Cho),김종묵(Jong-Mook Kim ),김병문(Byong-Moon Kim),김선영(Sunyoung Kim) 大韓藥學會 2001 약학회지 Vol.45 No.1

We recently developed a high dfficiency expression vector, pCK, which drives a high level of gane expresion in the skeletal muscles of mice. In this study, we investigated the pharmacokinetics and biodistribution of pCK-VEGF expressing human VEGF165 after intravenous or intramuscular administration. The quantity of pCK-VEGF in the tissues of mice was measured by the PCR method which has a detection limit of approxinately 1 pg of the exogenously added plasmid In the case of intravenous administration, the half life of the pCK-VEGF plasmid in the bloodstream was 1.68 min. After inter-muscular adminstration, the half life of pCK-VEGF plasmid in the bloodstrean was 6.78 min. At 90 min post-administration, 30% of the injected pCK-VEGF was found at the site of injection, where it persisted for up to 8 hours. Less than 1.6% of the injected pCK-VEGF plasmid DNA was detected in highly vascularized tissues such as the lung, kidney, and liver at 90 min post-administration administrated pCK- VEGF presisted for longer periods of time in muscls than in other tissues and that direct intra-muscular injection of pCK-VEGF might be useful for local therapeutic angiogensis.

에탄올 - 유발 위점막손상에 대한 애엽추출물 (DA-9601) 의 방어효과 및 기전에 관한 연구

안병옥(Byoung Ok Ahn),김원배(Won Bae Kim),김순회(Soon Hoe Kim),이은방(Eun Bang Lee),오태영(Tae Young Oh),류병권(Byung Kweon Ryu),고준일(Jun Il Ko),손미원(Mi Won Son) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.2

Protective effect of DA-9601, an extract of Artemisia Herb, against ethanol-induced gastric mucosal injury was evaluated in rats. In the prophylactic study, DA-9601 exhibited total protection (99.4%) against absolute ethanol-induced gastropathy. And the protective effect of DA-9601 lasted up to 2 hours, which was longer than those of other contemporary mucoprotectants. In the treatment study, DA-9601 significantly facilitated the healing of 70% ethanol-induced mucosal damage, which was superior to cetraxate, a commonly used anti-ulcer drug. The mechanisms of mucoprotection of DA-9601 were also assessed. DA9601 increased the release of prostaglandin E₂ from murine neutrophils in a dose-dependent manner in vitro. The cytoprotective effect of DA-9601 against ethanol-induced mucosal damage was significantly diminished by the concommitant injection of N_w-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg, i.v.), a non-specific nitric oxide (NO) synthase inhibitor, while it was not affected by preinjection of indomethacin (5 mg/kg, s.c.), a prostaglandins-depletor. And it was found that DA-9601 significantly enhanced adaptive cytoprotective action of 10% ethanol against absolute ethanol (56.9±6.5 vs 23.0±3.3 mm², p<0.05, mean±SEM), though its exact underlying mechanism remains to be clarified. The present findings demonstrate that DA-9601 exerts gastroprotective actions for the stomach against ethanol through several different underlying mechanisms, in which prostanglandins and NO are involved. In conclusion, the results obtained suggest that DA-9601 can be useful both in prevention and treatment of ethanol-induced gastric damage.

새로운 플라보노이드 유도체인 DA-6034의 TNBS 유발성 염증성대장염 모델에서의 치료효과

손미원,고준일,김희기,장동경,유무희,김원배,이강춘,송인성 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1

The efficacy of DA-6034, a new flavonoid derivative, was investigated in comparison with sulfasalazine in a trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. Under light anaesthesia with ether, rats were subjected to intracolonic administration of 30㎎ TNBS in 50% ethanol (0.5㎖) and were then sacrificed at 7 or 21 days after colitis induction. The TNBS control group (the saline treated colitic rat) exhibited ulceration and inflammation of the distal colon with formation of granuloma and pathologic connections. Moreover, an increase in colonic myeloperoxidase (MPO) activity (investigated as an index of leukocyte adhesion and accumulation) and an elevated colonic leukotriene B_4(LTB_4) level were observed. The colitic rats received DA-6034 (0.3∼30㎎/㎏) or sulfasalazine (50∼100㎎/㎏), prednisolone (0.3∼3㎎/㎏) after the induction of colitis until they were sacrificed. Oral treatment with DA-6034 resulted in significant reductions of macroscopic colonic damage, colonic inflammation. DA-6034 had a more potent effect than sulfasalazine and prednisolone on macroscopic colonic damage, while it has similar effect with prednisolone on the reduction of colonic LTB_4 synthesis and MPO activity. This study show, therefore, that DA-6034 is effective in attenuating the colonic lesion in an TNBS-induced colitis model. Furthermore, the results suggest that the effect of DA-6034 is partially related to its action on LTB_4 synthesis and MPO inhibition.

염증성 장질환 실험동물모델에서 Flavonoids 유도체 DA-6034 경구 치료의 효과

김태호,김유선,송인성,정현채,손미원,고준일,김정룡,김원배 대한소화기학회 1999 대한소화기학회지 Vol.34 No.3

Background/Aims: Eupatilin, a kind of flavonoids, has been known to be effective for chronic diarrhea in Korea. We performed this study to evaluate the oral therapeutic effect of DA-6034, a synthetic derivative of Eupatilin, in two experimental animal models. Methods: The Sprague- Dawley rats were used. Trinitrobenzene sulfonic acid (TNBS)-enteritis was induced by injection of TNBS solution at distal ileum after laparotomy. Then, the subjects were categorized into four groups. Each group was administered orally saline, 3 mg/kg of DA-6034, 1 mg/kg of prednisolon (Pd) or 100 mg/kg of sulfasalazine, respectively, for 2 weeks. HLA-B27 transgenic rats, in which spontaneous colitis is known to develop, were categorized into three groups and each group was administered orally saline, 3 mg/kg of DA-6034 and 0.5 mg/kg of Pd for 6 weeks. The therapeutic effects were assessed by gross and microscopic damage score and the level of leukotriene B₄ (LTB₄) and prostaglandin E₂ (PGE₂). Results: In TNBS-enteritis induced rats, the gross damage score and the level of LTB₄ of the groups treated with DA-6034, Pd, and sulfasalazine were significantly lower than those of saline group (p$lt;0.05). However, there was no difference among those of the treatment groups. In HLA-B27 transgenic rats, the microscopic damage score of treatment groups was significantly decreased compared with saline group (p$lt;0.05) and the level of PGE₂ showed decreasing tendency. Conclusions: DA-6034 has significant therapeutic effects on two animal models with inflammatory bowel disease. Therefore, it is worth to have human trial for the patients with inflammatory bowel disease.