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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.
박종희,문전옥,Park, Jong-Hee,Moon, Jeon-Ok 한국생약학회 1997 생약학회지 Vol.28 No.3
For the search of hepatoprotective compounds from the folk medicines, 14 natural products which have been traditionally used as hepatoprotective drugs in Korea were extracted with methanol. The extracts were screened for the antioxidant activity on lipid peroxidation induced by Fenton reaction in rat homogenate and Ac2F cell toxicity by t-hydroperoxide. Dendrobium moniliforme and Castanea crenata were chosen for the further investigation and its therapeutic effects on the liver damage induced by carbon tetrachloride in rats were evaluated. Oral administration of the extracts reduced the aspartate aminotransferase(AST) and alanine aminotransferase(ALT) activities in the serum of the carbon tetrachloride intoxicated rat. And the treatment of the extracts prevented the decrease of aminopyrine N-demethylation and aniline hydroxylation activities of the carbon tetrachloride-intoxicated rat liver. These results suggest that oral administration of Dendrobium moniliforme and Castanea crenata is effective in recovering the liver function in $CCl_4-treated$ rats.
한지아,김진수,문전옥,채소청,박종희,Han, Jee-Ah,Kim, Jin-Soo,Moon, Jeon-Ok,Cai, Shao-Qing,Park, Jong-Hee 한국생약학회 1997 생약학회지 Vol.28 No.3
Korean folk medicine 'O-I-Pul' has been used to cure arthritis, neuralgia, leucorrhea, snake-bite, vomiting and diarrhea. With regard to the botanical origin of O-I-Pul, it has been considered to be Sanguisorba species of Rosaceae, but there has no pharmacognostical confirmation on it. Morphological and anatomical examination of Sanguisorba leaves show that 'O-I-Pul' was the leaves of S. Officinalis and S. tenuifolia var. alba.
새로운 항산화제 검색법에 의한 SOD Mimic 천연 약물의 개발-상백피의 항염증효과
정경욱,남경수,박종희,문전중리,문전옥,Cheong, Kyoung-Ook,Nam, Kyung-Soo,Park, Jong-Hee,Kadota, Shigetoshi,Moon, Jeon-Ok 한국생약학회 1998 생약학회지 Vol.29 No.1
Aqueous extract of Morus alba L. blocked the toxic effect of paraquat on E. coli growth. The active components in the extract may be capable of crossing the cell membranes and protect against superoxide toxicity in E. coli, The extract inhibited $FeSO_4/H_2O_2$ induced lipid peroxidation in rat liver homogenate and protected against t-butyl hydroperoxide caused Ac2F cell damage. Moreover, the extract showed inhibitory effect on phospholipase $A_2$ activity in a dose dependent manner. Antiinflammatory effect of the extract was further investigated using the carrageenin-induced oedema model. A single adminstration of the extract (3g/kg body, p.o.) was more effective than indomethacin. These results suggest that the isolation and identification of the active components would have significant therapeutic application to inflammation associated with oxygen radicals.
새로운 간염치료제인 수용성 DDB 유도체 (DDB-S)의 항원성 평가
한형미,김진호,최경백,김형수,정승태,문전옥,이치호,김주일,Han, Hyung-Mee,Kim, Jin-Ho,Choi, Kyoung-Baek,Kim, Hyung-Soo,Chung, Seung-Tae,Moon, Jeon-Ok,Lee, Chi-Ho,Kim, Joo-Il 한국독성학회 1998 Toxicological Research Vol.14 No.3
Dimethyl dimethoxy biphenylate (DDB) is an agent used to treat hepatits. DDB-S (DDB-soluble), a new DDB derivative, was synthsized to increase water solubility of the original DDB. In the present study, the antigenic potential of DDB-S was examined by active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA) and passive hemagglutination (PHA) tests. The experimental groups consist of a low dosage group, a high dosage group, he group emulsified with Freund's complete adjuvant (FCA, ASA test) or an alum (PCA and PHA tests) and the macromolecule conjugate group emulsified with FCA or an alum. In the ASA test, all experimental groups showed negative responses whereas the positive control group given ovalbumin plus FCA showed severe anaphylactic responses. In the heterologous PCA test using mice and rats, positive responses were not detected in any of the experimental groups. In the PHA test, all experimental groups showed negative responses whereas the positive control group given ovalbumin plus an alum showed 512~2048 PHA titers. These results demonstrated that DDB-S does not have any antigenic potential. These can be utilized as a part of preclinical data for the development of DDB-S as an intravenous injection.
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.
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.