Nifedipine 투여가 선천성 고혈압 쥐의 CYP1A1과 2B1 유도에 미치는 영향

홍영숙,김형래,박혜영,배영숙,박상신 梨花女子大學校 醫科大學 醫科學硏究所 1995 EMJ (Ewha medical journal) Vol.18 No.3

Cytochrome P-450(CYP) enzymes are important in catalyzing the hiotransffrmation on manyendogeneous compounds and xenobiotics, including drugs and carcinogens. In the presentstudy, effect of nifedipine a voltage dependent calcium channel blocker on the induction ofCYP1A1 and 2B1 was investigated. Change of CYP1A1 and 2B1 activities were measuredby using specific enzyme activities and Western blot analysis. CYP1A1, as quantified by ethoxyresorufin-0-deethylase activity and Western blot with monoclonal antibody 1-7-1, increasedin liver microsome of nifedipine-treated spontaneous hypertensive rat(SHR. 30mg/kg.b.w, twicea day for 3days) but not in kidney microsome. CYP2B1, as quantified by benzyloxyresorufin-O-dealkylase activity and Western blot wit]1 monoclonal antibody 2-66-3, markedly increasedin liver microsome of nifedipine-treated SHR but slightly in kidney microsome. The resultsdemonstrate that nifedipine is a potent inducer of CYP2B1 in SHR.

茵蔯蒿의 膽汁分泌 機轉에 관하여

裵玲淑,洪永淑 梨花女子大學校 韓國生活科學硏究院 1980 韓國生活科學硏究院 論叢 Vol.25 No.-

漢方 및 민간에서 흔히 黃疸 치료에 사용하는 菌蔯蒿를 家兎에 투여하여 다음과 같은 결론을 얻었다. 1) 담즙 분비량은 菌蔯蒿 투여군에서 대조군에 비해 별다른 변화가 없었다. 2) 담즙 biliverdin은 菌蔯蒿 투여군에서 상당히 증가된 치를 나타내었다. 3) 담즙 cholate 치는 菌蔯蒿 투여군이나 대조군이 비슷하였다. 4) 담즙 cholesterol 치는 菌蔯蒿 투여군이 대조군에 비해 별 변화가 없었다. 5) 간장 microsome 內 cytochrome p-450은 菌蔯蒿 투여군에서 상당히 높은 치를 나타냄을 볼 수 있었다. Artemisia was used as folk medicine for hyperbilirubinemia. Kiku Tanni(1968) claimed that administration of Artemisia in patient with acute hepatitis, significantly lowered the bilirubin index, S.G.O.T and S.G.P.T. And Yokawa(1929) reported that I.V injection of Artemisia in rabbits revealed the increased volume of biliary juice. Therefore, ws decided to determine the mechamism of biliary excretion atter I.V. injection of Artemisia in rabbit. The results of this experiment were as follows:, 1. After I.V injection of Artemisia in rabbits, biliary juice volume was not increased than that of control group. 2. Biliverdin concentration in bile juice of rabbits treated with Artemisia significantly increased than that of control group. 3. Cholate and cholesterol concentration in bile juice of rabbit treated with artemisia was not increased than those of control group. 4. Liver microsomal cytochrome P-450 was increased significantly following Artenisia treat-ment.

Higenamine이 흰쥐 간조직 Mixed Function Oxidase System에 미치는 영향

홍영숙,배영숙,성낙응 梨花女子大學校 醫科大學 醫科學硏究所 1985 EMJ (Ewha medical journal) Vol.8 No.3

The effect of intraperitonelly administered higenamine on the cytochrome P -450, b_5, P-nitroanisole-O-demethylase and lipid peroxidation in the rat hepatic microsomes were determined. The following results were obtained ; 1) The intraperitonelly administered higenamine increased contents of rat hepatic microsomal cytochrome P-450 and b_5. 2) The principal role of cytochrome P-450 in mixed function oxidase reactions includes hydroxylation of various drugs, fatty acids, steroids, pesticides and carcinogens. The increased cytochrome P-450 induced by higenamine decreased on the both AAF of N-hydorxylation and Ring-hydroxylation. 3) Activity of P-nitroanisole-O-demethylase in hepatic microsomes with higenamine was decreased accorting to incresed dosage of higenamine. 4) The formation of lipid peroxides was increased according to increased dosage of higenamine.

고혈압성 흰쥐(Spontaneous Hypertensive Rat)에서 Nifedipine투여가 UDP-Glucuronosyltransferase에 미치는 영향

홍영숙,배영숙 이화여자대학교 생명과학연구소 1990 생명과학연구논문집 Vol.1 No.-

UDP-Glucuronosyltransferase(UDPGT) activity was studied in hepatic microsomal preparation from rats treated with nifedipine. The substrates 1-naphthol, P-nitrophenol, 4-methylumbelliferone and bilirubine were used. With 1-naphthol, nifedipine 2 and 4 weeks treatment caused 6-and 7.3-fold, respectively, increase in activity over the control value. With 4-methylumbelliferone, nifedipine 2 and 4 weeks treatment caused 5-and 6-fold increase in activity over the control value. With P-nitrophenol, nifedipine 2 and 4 weeks treatment caused both approximately 3-fold increase in activity over the control value. However bilirubin-UDPGT activity was not affected by this inducer effects of nifedipine on the hepatic monooxygenase system in rats were investigated. P-Nitroanisole-O-demethylase, NADPH-cy-singificantly increased to 390,290 and 150% of control rats, respectively. The selectivity of nifedipine of UDP-glucuronosyltransferase was investigated in rat liver microsomes and compared with their effect on monooxygenase reactions. Similar to 3-meth-lycholanthrene-type seletively stimulated the glucuronidation induced both UDPGT_1 and monooxygenase activity, probably through a common receptor protein.

Higenamine이 가토肝組織 Cytochrome酵素系와 Lipid Peroxidation에 미치는 影響

洪永淑,裵玲淑 梨花女子大學校 韓國生活科學硏究院 1985 韓國生活科學硏究院 論叢 Vol.36 No.-

미나리아재비과에 속하는 다년생 식물인 부자는 한방에서 강심, 이뇨 및 진통등의 목적으로 사용되어 왔다. 이들 부자屬 식물의 잎, 줄기 및 뿌리에는 aconitine계 알칼로이드들이 다량 함유되어 있으며 이들은 독성이 매우 강하다. 이 부자에서 강심작용이 있는 higenamine이 분리되였다. 분리된 higenamine의 강심효과 뿐만 아니라 간조직 microsomal cytochrome enzyme system에 미치는 효과를 관찰 하고자 하였다. Hepatic microsomal cytochrome P-450과 NADPH-cytochrome C reductase함량 그리고 p-nitroanisole-O-demethylase의 활성과 lipid peroxidation을 측정하여 다음과 같은 결론을 얻었다. 가토 뇌측실내로 higenamine을 주입한 후 hepatic microsomal cytochrome P-450함량과 NADPH-cytochrome C reductase활성은 감소 하였고 haloperidol과 bethanechol 투여군에서는 이들의 활성이 증가되였다. Hepatic microsomal p-nitroanisole-O-demethylase활성은 증가되었고 haloperidol 단독 투여군이 가장 많이 증가되였다. Hepatic microsomal lipid peroxide형성은 증가 되였으나 haloperidol과 bethanechol단독 투여군은 감소 되였다. 이상과 같이 가토 뇌측실내로 higenamine투여는 강심효파 뿐만아니라 hepatic microsomal cytochrome 효소계에도 영향을 미침을 알수 있었다 Aconitic root from Aconitum japonicum has long been used as one of the most important herbs as a heart stimulant, diuretic agent, and anodyne in Chinese medicine. Higenamine, which has recently been isolated from the Aconitic root, would have agonistic activity. The effect of centrally administered Higenamine by concomitant administration of haloperidol and bethanechol on the cytochrome P-450, NADPH-cytochrome C reductase, p-Nitroanisole-O-demethylase and lipid peroxidation in the rabbit hepatic microsomes were determined. Marked decrease of cytochrome P-450 content and NADPH-cytochrome C reductase activity were produced. Pretreatment with haloperidol was effective in the blockade of decrease of cytochrome P-450 content. Administration of higenamine, haloperidol and bethanechol caused increases in specific activity of p-nitroanisole-O-demethylase. Higenamine increased lipid peroxidation and the increased effect of higenamine was blocked completely by both haloperidol and bethanechol pretreament. These results indicated that higenamine showed effect not only agonistic activity, but also cytochrome enzymes activity and lipid peroxidation in the rabbit hepatic microsomes.

고혈압성 흰쥐(Spontaneous Hypertensive Rat)에서 Nifedipine투여가 UDP-Glucuronosyltransferase에 미치는 영향

홍영숙,배영숙 梨花女子大學校 醫科大學 醫科學硏究所 1990 EMJ (Ewha medical journal) Vol.13 No.2

UDP-Glucuronosyltransferase(UDPGT) activity was studies in hepatic microsomal preparation from rats treated with nifedipine. The substrates 1-naphthol, P-nitrophenol, 4-methyl-umbelliferone and bilirubine were used. With 1-naphthol, nifedipine 2 and 4 weeks treatment caused 6- and 7.3-fold, respectively, increase in activity over the control value. With 4-methylumbelliferone, nifedipine 2 and 4 weeks treatment caused 5- and 6-fold increase in activity over the control value. With P-nitrophenol, nifedipine 2 and 4weeks treatment caused both approximately 3-fold increase in activity over the control value. However bilirubin-UDPGT activity was not affected by this inducer effects of nifedipine on the hepatic monooxygenase system in rats were investigate. P-Nitroanisole-O-demethylase, NADPH-cytochrome C reductase activity and cytochrome P-450 content in nifedipine treated rats were significantly increased to 390, 290 and 150% of control rats, respectively. The selectivity of nifedipine of UDP-glucuronosyltransferase was investigated in rat liver microsomes and compared with their effect on monooxygenase reactions. Similart o 3-meth-lycholanthrene-type selectively stimulated the glucuronidation induced both UDPGT_1 and monooxygenase activity, probably through a common receptor protein.

Naloxone이 흰쥐 간조직의 Mixed-Function Oxidation과 Lipid Peroxidation에 미치는 영향

홍영숙,성낙응,배영숙 梨花女子大學校 醫科大學 醫科學硏究所 1986 EMJ (Ewha medical journal) Vol.9 No.3

The effects of Naloxone, narcotic antagonist, pretreated with normal saline, salicylate and hydrocortisone produced by with hypovolemic shock on the rates of cytochrome components, mixed function oxidation enzyme reactions and lipid peroxidation have been determined using hepatic microsomal fractions of rats. The treatments with either of the naloxone have increased the contents of cytochrome P-450 and b_5 and NADPH- or NADH-cytochrome C reductase. But pretreated with salicylate and hydrocortisone were not change as compared to the control. The rates of O-demethylation for p-nitroanisole were decreased. Naloxone decreased the formation of lipid peroxide by pretreated salicylate and hydrocortisone. These results indicate that naloxone showed effect not only increase of blood pressure and respiration, but also cytochrome components activity, mixed function oxidation enzyme reactions and lipid peroxidation in the hepatic microsomal fractions of rats.

Carbon tetrachloride, Phenobarbital 및 인진호를 투여한 흰쥐에서 Vitamin Antioxidants가 Lipid Peroxidation에 미치는 영향

한은경,홍영숙,성낙응,배영숙 梨花女子大學校 醫科大學 醫科學硏究所 1983 EMJ (Ewha medical journal) Vol.6 No.2

After rats were treated with CC1_4, phenobarbital and artemisia messes-schmiaiana var viridis(artemisia), hepatic microsomal cytochrome P-450, cytochrome b_5 and lipid peroxidation were investigated. When vitamin A, C and E were added incubation medium in each group respectively, lipid peroxidation was observed. The results were as follows. 1) When administrated with CC1_4 in rats, the contents of total microsomal cytochrome P-450 and cytochrome b_5 were decreased by 58% and 36%, respectively. And lipid peroxidation was decreased to by 6%. 2) When administrated with phenobarbital and artemisia. in rats respectively, the contents of total microsomal cytochrome P-450 and cytochrome b_5 were increased by 25 to 135%. And lipid peroxidation was increased by 30 to 57%. 3) When administrated with CC1_4 and phenobarbital or artemisia. in rats, the contents of total microsomal cytochrome P-450 and cytochrome b_5 were increased by 8 to 35%. And lipid peroxidation was increased by 4 to 14%. 4) When vitamin A, C and E incubated in each group in each group in vitro, lipid peroxidation were decreased by 3 to 87%. And th higher concentrations of vitamin A, C and E were, the more lipid peroxidation was decreased. These results indicate that vitamin antioxidants can prevent lipid peroxidation in CC1_4, phenobarbital, CC1_4 with phenobarital. artemisia. and CC1_4 with artemisia.-pretreated rat liver microsomes.

DIFFERENTIAL INDUCTION OF RAT LIVER MICROSOMAL CYTOCHROME-DEPENDENT MONOOXYGENASE AND UDP-GLUCURONOSYLTRANSFERASE ACTIVITIES BY VARIOUS NARCOTIC DRUGS

Hong, Young-Sook,Pae, Young-Sook The Korean Society of Toxicology Korea Environment 1989 Toxicological Research Vol.5 No.1

Chronic adminstraction of morphine to adult male rats has long been known to lower hepatic cytochrome p-450 content and its dependent mixed-function oxidase activity. Following the treatment of adult male rats with morphine, pethidine pentazocine and codeine and also by concomitant adminstration of naloxone activities of microsomal electron transfer in the adult male rats were examined. In present study, the acute treatment of mature male rats with a dose of narcotic drugs higher than that used chronically also reduces their hepatic cytochrome p-450.

취외분비선에 미치는 사염화탄소의 영향

배영숙(Young-Sook Pae) 대한약리학회 1975 대한약리학잡지 Vol.11 No.1

The metabolism of many drugs and also of steroid hormones is mediated by enzymes located in the microsomal fraction in smooth surfaced endoplasmic reticulum of mammalian liver. The duration and intensity of action of many drugs are largely determined by the speed at which they are metabolized in the body. Repeated administration of phenobarbital results in the induction of enzymes that metabolize a number of drugs. Lee et al. reported that daily administration of phenobarbital in rats significantly increased the activities of amylase in the pancreatobiliary juice, but the concentration of cholate in the bile was significantly lower in the treated group than that in the control group. After animals were treated with CCl₄, histological changes were shown in the endoplasmic reticulum, decreased microsomal enzyme activity and decreased hepatic protein synthesis were apparent. The purpose of the present report was to study the interaction between a microsomal-stimulating agent such as phenobarbital and a microsomal- depressing agent such as CCl₄ on hepatic and pancreatic functions in rats. The results obtained are summarized as follows: 1. The mortality rate of CCl₄ treated group was 34% and was decreased this figure to 15% with phenobarbital pretreatment. 2. In animals treated with phenobarbital the volume of biliary-pancreatic secretion was markedly elevated but the volume was decreased significantly in animals treated with CCl₄. 3. Total bilirubin output was elevated markedly in the CCl₄ treated group of rats pretreated with phenobarbital. The bilirubin concentration was increased in CCl₄ treated group and decreased in the group treated phenobarbital alone. 4. The concentration and total output of cholate in the bile were significantly lower in the all experimental group than control group. 5. In the animals treated with phenobarbital alone and phenobarbital plus CCl₄, the activity of lipase in pancreatobiliary juice was elevated, while in the animals treated with CCl₄ alone no change was observed. 6. The activity of amylase in the pancreatobiliary juice was decreased in the CCl₄ treated group, but elevated markedly in phenobarbital group and also elevated in phenobarbital-CCl₄ group. By the above results, it is concluded, when the liver was damaged by CCl₄, the exocrine function of pancreas and liver was decreased simultaneously. However, in the animals pretreated with phenobarbital, the toxicity of CCl₄ on the liver and pancreas was reduced.