Cytochrome P-450유도가 간세포의 지질과산화와 산소소비에 미치는 영향

문전옥 부산대학교 신약개발연구소 1993 藥學硏究誌 Vol.27 No.1

The reates of the NADPH-dependent oxygen consumption by the liver S-9 mixture and microsomes were determined. The rates by the liver S-9 mixture and microsomes from phenobarbital pretreated rats were 9-12 times and 2.4-2.9 times higher than rates by the liver S-9 mixture and microsomes from non-treated rats, respectively. Pretreatment with phenobarbital increased the thiobarbituric acid reactive substances formation and the NADPH oxidation in the liver compared with the non-treated rats. On the other hand, the rates of the NADH-dependent oxygen consumption decreased in the liver S-9 mixture and microsomes from phenobarbital pretreated rats and it is consistent with oxidation of NADH. Neverthelese, the NADH-dependent formation of TBA reactive substances in the liver S-9 mixture and microsomes increased in phenobarbital pretreated rats. These results suggest that alteration in the liver microsomal component such as cytochrome P-450 and cytochrome P-450 reductase effects on the oxygen consumption by autooxidation in the liver and lipid peroxidation of the liver.

활성산소종에 의한 알데히드 탈수소 효소의 불활성화

문전옥,김태완,백기주,김기헌 대한약학회 1993 약학회지 Vol.37 No.6

The susceptibilities of aldehyde dehydrogenase (AldDH) and alcohol dehydrogenase (ADH) to active oxygen generated by xanthine-xanthine oxidase (XOD) system were studied. Incubation of AldDH with 2$\times$10$^{-3}$ units of XOD for 30 min at $25^{\circ}C$ resulted in the decrease of enzyme activity to 30% and it was inactivated completely when incubated with 5$\times$10$^{-3}$ units of XOD. Whereas 70% of ADH activity was retained after exposure to 5$\times$10$^{-3}$ units of XOD for 30 min, 40% of ADH activity was retained after exposure to 5$\times$10$^{-2}$ unit of XOD for 30 min. This inhibition effect by the active oxygen was preventable by catalase and glutathione, but not by SOD. The rates of the NADPH-dependent oxygen consumption by the liver S-9 mixture and microsomes were also determined in this study. Rate of oxygen consumption is increased in the liver S-9 mix and microsomes from phenobarbital-treated rat, and it was consistent with increased lipid peroxidation. In the presense of ethanol as a substrate, the oxygen consumption rates were increased. It is reported that hepatic AldDH activity is depressed in alcoholic liver diseases, however there is few report that explains the reason of depressed AldDH activity. These results are supportive of the theory that the increase in hepatic ethanol oxidation through the induced ME activity after chronic ethanol feeding generate oxygen radical at elevated rates and it leads to the depression of AldDH activity.

Mechanism of Alcoholic Liver Disease

문전옥 한국생명과학회 1994 생명과학회지 Vol.4 No.3

알콜성 간장해의 발생, 진전에는 많은 인자가 관여하고 있으며 극히 복잡한 병태를 형성하는데 그 기전으로는 1)간내 [NADH]/[NAD] 비의 상승, 2)에탄올의 주 대사산물인 아세트알데히드에 의한 간장해, 3)면역기구에 의한 간장해, 4)과산화지질, 활성산소 및 free radical 에 의한 장해와 5) 중심정맥역의 hypoxia에 의한 간세포장해 기전을 들 수 있다. 본 총설에서는 알콜을 장기 섭취할 경우 간에서의 대사경로와 현재 고려되고 있는 몇 가지 알콜성 간장해 발생기전에 대한 최근의 연구들을 정리하였다.

肝내 알데히드 탈수소효소 활성의 변동

문전옥,김태완,백기주,김기헌 부산대학교 신약개발연구소 1994 藥學硏究誌 Vol.28 No.1

It was reported that hepatic aldehyde dehydrogenase(ALDH) activity was depressed in alcoholic liver diseases, however there was few report that explain the reason of depressed ALDH activity. We have attempted to correlate the decrease of hepatic ALDH activity with the active oxygen species which generated at elevated rates in the proliferated microsomes by chronic ethanol feeding. The susceptibilities of the hepatic ALDH activity to active oxygen generated by xanthine-xanthine oxidase system and FeSO₄-H₂O₂ system were studied. Incubation of ALDH with 2×10³ xanthine oxidase for 30 min at 25℃ resulted in the decrease of enzyme activity to 60%, and 55% of ALDH activity was retained after exposure to FeSO₄4-H₂O₂ system for 20 min. Alteration in the ALDH activity after administration of ethanol in rat liver was investigated. Whereas the mitochodrial ALDH activity was increased, the microsomal activity was depressed in ethanol-treated rat. Induced microsomal ALDH activity was observed by treatment of phenobarbital or 3-methylcholanthrene in the liver of rats chronically fed alcohol. Since the ALDH catalyses the oxidation of a wide variety of aliphatic and aromatic aldehydes, it is suggested that the alteration in the ALDH activity by various factors including the active oxygen affects the physiological states of liver administrated ethanol chronically, which may in turn to lead to liver disease.

간 상해제에 의한 알데히드 탈수소효소의 변동

문전옥,양정화 부산대학교 신약개발연구소 1995 藥學硏究誌 Vol.29 No.2

We produced in vivo hepatitis in rat by applying hepatotoxicants such as CCl₄, allyl alcohol, galactosamine and phenobarbital. Then we focused on the alterations of the microsomal P450 activity, TBA reactive substances, the content of non-protein SH and the activities of alcohol dehydrogenase and aldehyde dehydrogenase in rat liver. Whereas the ADH activity was not altered except in the case of CCl₄, the mitocondrial and microsomal ALDH activities were decreased by the treatment of the hepatotoxicants and it was consistent with the increase of TBA reactive substances formation and the decrease of the non-protein SH content.

Hydroperoxide 의존성 반응에서의 Cytochrome P-450의 산화활성종 형성양식

문전옥(Jeon Ok Moon),김기헌(Ki Heun Kim) 대한약학회 1993 약학회지 Vol.37 No.1

Peroxidase activity of cytochrome P-450 was examined using N, N-dimethylaniline (NDA) as a substrate and cumene hydroperoxide (CHP) as an oxidant. The initial rates of the N-demethylation for varied concentrations of NDA (0.05-0.5 mM) by P-450 at different fixed concentrations of CHP (0.02-0.2 mM) were determined. The results suggest that P-450 proceeds its peroxidative reaction by the rapid equilibrium random bi bi mechanism to form a ternary complex with substrate and oxidant as an active intermediate.

만성 알콜 섭취로 인한 간내 알데히드 탈수소 효소 활성의 변동

문전옥(Jeon Ok Moon),양정화(Jeong Hwa Yang) 대한약학회 1996 약학회지 Vol.40 No.5

The system most likely responsible for the accelerated metabolism of alcohol with chronic ingestion or at high blood ethanol levels, is the microsomal ethanol-oxidizing system(MEOS). While the increase in the MEOS with chronic ethanol ingestion is thought to be adaptive, it may also have serious adverse effects on the liver. The rates of the NADPH-dependent oxygen consumption by the liver microsomes from the prolonged ethanol fed rats were 2 times higher than the rates from the non-treated rats. With the alcohol ingestion, the total SH and nonprotein SH contents showed the significant decrease and at the same time, MDA in liver and GOT and GPT levels in blood showed the significant increase, which suggests the occurrence of liver damage due to the oxidative stress caused by chronic alcohol consumption. The mitochondrial aldehyde dehydrogenase(ALDH) activity was decreased by chronic ethanol ingestion, whereas the alcohol dehydrogenase activity and the cytosolic ALDH activity were not altered. These results suggest that the induction of cytochrome P450 by the chronic alcohol ingestion increases the oxidative stress which seems to result in the altered the physiological states of the liver including the ALDH activity, which may in turn to lead to the liver disease.

알데히드 탈수소 효소 활성에 미치는 글루타치온의 영향

이은실,문전옥 한국환경독성학회 2001 환경독성보건학회지 Vol.16 No.1

It is known that alcoholics have significantly lower mitochondrial aldehyde dehydrogenase (ALDH)s' activity than do normal subjects or nonalcoholics with liver disease. However, there are only few reports that explain the reasons behind this reduction of ALDHs' activities. In this study, ALDH activity is inhibited by acetaldehyde, a substrate for ALDH. However, the addition of glutathione (GSH) protected ALDH activities against the inhibitory effects of acetaldehyde in vitro. Furthermore, when GSH depletion is induced using diethyl maleate (DEM) in rats by 24% in cytosol and 43% in mitochondria, ALDH activities were also depressed by 31% and 63%, respectively compared to non-treated rats without significant reductions in other hepatic enzymes. These results suggest that ALDHs' activities are closely related to the concentration of acetaldehyde and/or cellular GSH contents. Therefore in alcoholic liver disease, increased productions of acetaldehyde and decreased contents of mitochondrial GSH may involved in the depression of ALDHs' activities.

Isoflavone glycosides from the flowers of Pueraria thunbergiana

Jung, Won-Tae,Moon, Jeon-Ok,Park, Hee-Juhn,Oh, Sei-Ryang,Park, Jong-Hee,Lee, Hyeong-Kyu,Lee, Kyung-Tae WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 1999 東西醫學硏究所 論文集 Vol.1999 No.-

Two new isoflavone glycosides together with glycitein, tectoridin and glycitin, were isohted from the flowers of Pueraria thun-bergiana. These structures were determined as 4',7-dihydroxy-6-methoxyisoflavone 7-O-β-D-xylopyranosyl-(1->6)-β-D-gluco-pyranosie And 4',5,7-trihdroxy-6-methoxyisoflavone 7-O-β-D-xylopyranosyl-(1->6)-β-D-glucopyranoside.

수용성 Dimethyl Dimethoxy Biphenylate 유도체의 간염 치료 효과

이치호,문전옥,정경욱,김수현,김남득,이성광,양희선 한국약제학회 1997 Journal of Pharmaceutical Investigation Vol.27 No.3

A water-soluble DDB derivative (Bis{2-(methylamino)ethyl}-4.4-dimethoxy-5.5', 6.6'-dimethylene-dioxy-biphenyl-2,2'-dicarboxylate, DDB-S) was synthesized and its therapeutic effects on the liver damage induced by carbon tetrachloride in rats were evaluated. Oral administration of DDB-S reduced the aspartate aminotransferase(AST) and alanine aminotransferase(ALT) activities and increased total protein and albumin contents in the serum of the carbon tetrachloride intoxicated rat. Therapeutic effects of DDB-S by intravenous injection was also investigated using carbon tetrachloride intoxicated rats. Histological studies showed that IV injection of DDB-S had improved the typical necrosis around centrilobular area in liver tissue due to the carbon tetrachloride intoxication and also prevented the elevation of liver weight/body weight ratio. IV administration of DDB-S to CCl₄-treated rats significantly decreased AST & ALT activities and also prevented the decrease of aniline hydroxylation activity of the liver. These results indicate that i.v. administration of DDB-S is very effective in recovering the liver function in CCl₄-treated rats.