• 약학회지
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• 제31권6호
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• pp.361-369
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• 1987

The four azo dyes such as Amaranth (FD & C Red No. 2), Tartrazine (FD & C Yellow No. 4), sunset Yellow (FD & C Yellow No. 5) and Allura red (FD & C Red No. 40) are currently employed as a food additives in Korea. In this study, the effects of these azo dyes on the hepatic microsomal mixed function oxidase systems in Rats. (i.e., Cyt. P-450, Cyt. b$_5$, NADPH cyt. c-reductase and azo reductase) were investigated. Furthermore, to determine the relationship among the electron transport systems, each level of azo reductase, Cyt. P-450 and NADPH cyt. c-reductase was measured upon the administration of phenobarbital (known as an inducer of Cyt. P-450), 3-methylcholanthrene (Known as an inducer of Cyt. P-448), CoCl$_2$ (inhibitor on Cyt. P-450) or $CCl_4$ (inhibitor on Cyt. P-450). The results of these studies are as follows; (1) The levels of Cyt. P-450 and Cyt. b$_5$ were decreased upon the administration of these azo dyes. (2) When the level of Cyt. P-450 was decreased, the azo reductase activity was also decreased. (3) These azo dyes did not show any significant effect on the level of NADPH cyt. c-reductase. (4) The administration of 3-methylcholanthrene resulted in the elevation of azo reductase activity. The 3-methylcholanthrene may be responsible for the induction of CO-insensitive electron transport system.

• Journal of Nutrition and Health
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• 제25권1호
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• pp.3-11
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• 1992

This paper examines the effects of dietary fats on the fatty acid composition and market enzyme activites during liver damage in 2-acetylaminofluorene treated rats. Weaning Sprague-Dawley male rats were fed the diet of beef tallow(BT source of sturated fatty acid) corn oil(CO source of n-6 fatty acid) and perilla oil(PO source of n-3 fatty acid) at the level of 15% fat. Ten days after feeding 2-acetylaminofluorene(2-AAF) was injected intraperitoneally twice every week at the level of 50mg/kg body weight for 7 weeks. Liver microsomal and cytosolic fractions were collected to determine the microsomal fatty acid composition lipid peroxide(malondialdehyde MDA) contents glucose 6-phosphatase(G6 Pase) activity cytochrome(Cyt) P-450 contents and cytosolic glutathione S-transferase(G6 Pase) activity cytochrome(Cyt) P-450 contents and cytosolic glutathione S-transferase(GST) activity. The fatty acid composition in microsomal fraction was reflected by different dietary fats. By 2-AAF treatment linoleic acids were increased regardless of the diet MDA contents were higher in CO group than it was in BT group. However 2-AAF treatment decreased MDA contents in all dietary groups. G6Pase activity of BT group was higher than those of the other gropus. CO group had the highest Cyt P-450 contents and 2-AAF treatment lowered Cyt P-450 contents only in CO gropu GST activites were higher in CO than in BT group whereas the enzyme activites were increased by 20AAF treatment in all dietary groups. These results suggest that dietary fats and 2-AAF treatment in all dietary groups,. These results suggest that dietary fats and 2-AAF treatment affect microsomal fatty acid composition The enzyme activities concerned with liver damage were influenced differently by dietary fats and 2-AFF treatment Although PO diet contains much more polyunsaturated fatty acids than CO diet PO diet doesn't cause more oxidant stress compared with CO diet in these data.

• Toxicological Research
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• 제3권2호
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• pp.97-110
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• 1987

The effects of 5 novel hepatotrophic agents, dithiol malonate derivatives (DMDs; DMD1-DMD5), on the liver microsomal lipid peroxidation induced by carbon tetrachloride $(CCl_4)$ and the correlations with the changes of microsomal electron transport system were investigated. All DMDs were found to inhibit the lipid peroxidation induced by $CCl_4$ in mice and rats as well in vitro liver microsomal system. Therefore, each DMD seemed to have direct mode of action on liver microsomes to inhibit the lipid peroxidation. As an ex vivo study, the induced lipid peroxidation by $CCl_4$ and the changes in electron transport system were determined with liver microsomes obtained from rats chronically treated with DMDs for 7 days. The induced lipid peroxide contents in liver microsomal system were lower in DMD1, DMD2 and DMD3 treated group, but higher in DMD4 and DMD5 group when compared to the control group. Cyt. p.450 contents in the microsomes were decreased by the treatment with DMD1, DMD2 and DMD3, but increased significantly by DMD4 with great extent and by DMD5 with less extent. The cyt. p-450 isozymes induced by treatment of DMD4 and DMD5 were identified as 3-methylcholanthrene (MC) type. The NADPH cyt. -C reductase activities of the microsomes treated with DMD1, DMD2, DMD4 and DMD5 were increased in the range of around 20% to 50%, but decreased with DMD3, All DMDs increased dyt. $-b_5$ content and did not alter NAdH-cyt, $-b_5$ reductase activities in the microsomes. In summary, the 5 novel hepatotrophic agents (DMDs) markedly protected against lipid peroxidation induced by $CCl_4$ in vivo and in vitro possibly through the mechanism of direct action on the liver microsomes. The degree of inhibition produced by DMDs on lipid peroxidation induced by $CCl_4$ seemed to coincide rather with cyt. p-450 contents than with other components of liver microsomal electron transport system including NADPH-cyt, -C reductase.

• 식물조직배양학회지
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• 제25권3호
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• pp.141-146
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• 1998

[$^3$H] 5-epi-aristolochene (5-EAS)를 담배 현탁배양세포에 투여하여 elicitor에 의해 유도된 세포가 생합성하여 배지로 방출하는 [$^3$H]-capsidiol의 량을 측정함으로써 5-EAS hydroxylase의 활성을 검정하였고, 이 반응의 전 단계에 관여하는 효소인 sesquiterpene cyclase의 발현특성과 비교하였다. 5-EAS hydroxylase는 정상세포에는 전혀 활성을 보이지 않으나 elicitor로써 cellulase를 처리한 세포는 9시간 후부터 유도를 시작하여 18시간 후에 최대 활성을 보였는데 동일한 세포내에서 유도되는 cyclase와 유사한 패턴을 보였다. Cyt P450계 효소의 특이적 억제제로 알려진 ancymidol과 ketoconazole에 의해 5-EAS hydroxylase의 활성은 강한 억제를 보인 반면 cyclase의 활성은 억제를 보이지 않아 5-EAS hydroxylase가 P450계 효소임이 시사되었다.

• 분석과학
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• 제5권1호
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• pp.83-90
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• 1992

$^{14}C$-warfarin을 흰쥐에 경구투여 후 4시간 경과시 혈액에서 최고치를 나타내었으며, coumarin과 그 유도체인 warfarin에 의한 간조직 microsome 내의 Cyt. p-450은 이들 화합물에 의해 microsomal electron transport system이 증가됨과 Cyt. p-450의 isozyme들이 유도됨을 확인할 수 있었다.

• 생명과학회지
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• 제8권5호
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• pp.604-613
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• 1998

담배의 phytoalexin으로 알려진 capsidiol 생합성의 마지막 단계에 관여하는 5-epi-aristolochene hydroxy-lase 유전자의 일부를 RT-PCR 방법으로 클로닝하였다. 클로닝한 CYP-B3는 콩, 완두 등의 cytochrome P450계의 유전자와 높은 동일성을 보였으며 heme 결합부위로 알려진 FxxGxRxCxG을 포함하고 있는 것으로 나타났다. 또한 CYP-B3는 저온, 고온 또는 제초제 등에 의해서는 유도되지 않고 Elicitor에 의해서만 특이하게 유도되는 것으로 나타나 Phytoalexin 생합성에 관여하는 유전자임을 확인하였다. Cyt P450 억제제인 ancy-midol과 ketoconazol에 의해 CYP-B3의 전사는 억제되지 않는 반면 5-epi-aristolochene hydroxylase의 효소활성은 현저히 억제되는 것으로 나타나 이들 억제제는 전사후의 효소의 합성 또는 활성을 억제하는 것으로 나타났다.

• Journal of Microbiology
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• 제40권3호
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• pp.211-218
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• 2002

A 4.8-kb DNA fragment encoding the P-450 type hydroxylase and ferredoxin genes was cloned from Pseudonocardia autotrophica IFO 12743 that can convert vitamin D$\_$3/ into its hydroxylated active forms. In order to isolate the P-450 gene cluster in this organism, we designed PCR primers on the basis of the regions of an oxygen binding site and a heme ligand pocket that are general characteristics of the P-450 hydroxylase. Sequencing analysis of the BamHI fragment revealed the presence of four complete and one incomplete ORFs, named PauA, PauB, PauC, and PauD, respectively. As a result of computer-based analyses, PauA and PauB have homology with enoyl-CoA hydratase from several organisms and the positive regulators belonging to the tetR family, respectively. PauC and PauD show similarity with SuaB/C proteins and ferredoxins, respectively, which are composed of P-450 monooxygenase systems for metabolizing two sulfonylurea herbicides in Streptomyces griseolus PauC shows the highest similarity with another CytP-450$\_$Sca2/ protein that is responsible for production of a specific HMG-CoA reductase inhibitor, pravastatin, in S. carbophilus. Cultures of Steptomyces lividans transformant, containing the P-450 gene cluster on the pWHM3 plasmid, was unable to convert vitamin D$\_$3/ to its hydroxylated forms.

• 한국자원식물학회지
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• 제31권5호
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• pp.531-537
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• 2018

국내 재배종 마늘을 대상으로 상처(wound) 처리에 특이적으로 발현되는 Cyt. P450 cDNA (ORF 1,419 bp) 중 1,210~1,240 bp 사이에 존재하는 heme-binding domain (HB-domain)의 염기서열 다형성을 바탕으로 국내산 재배마늘의 HB-domain의 다형성 분포를 조사하였다. 국내 재배마늘에서 7개의 각각 다른 염기서열을 가진 HB-domain 마커를 탐색하였고, 전국 6개 지역의 재배농가에서 임의로 수집한 120개 마늘의 마커 종류별 분포도를 조사하였다. 경북, 충남, 충북, 강원지역에서 재배되는 한지형 마늘은 아미노산서열 FGGGRRICPG, DNA서열 5'-TTT/GGC/GGT/GGA/CGG/AGA/ATA/TGT/CCT/GGA-3'인 KP2형의 HB-domain을 가진 재배종이 51.3%로 가장 많이 분포하였고, KP1형 13.7%, CP형 11.3%, CM형 8.8%, KW2형 5% 및 기타 1.3%인 것으로 나타났다. 경남지역 재배지에서 수집한 난지형 마늘은 아미노산서열 FGAGRRICPG, DNA서열 '5-TTT/GGC/GCA/GGA/CGG/AGA/ATT/TGT/CCT/GGA-3'인 KM형이 52.5%로 가장 많았고, KP2형 22.5%, KW2형 5%, KP1 및 CP형이 각각 2.5%가 분포하는 것으로 나타났으나 CM형은 존재하지 않았다. 이 결과는 우리나라에 재배되는 마늘은 유전적으로 상당히 혼재된 상태로 존재하며, 특정 지역을 대표하는 유전적 특징을 가진 재배종을 단정하기는 어려운 것으로 판단된다.

• Journal of Ginseng Research
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• 제13권1호
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• pp.37-41
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• 1989

Benzo(a)pyrene(BP)의 monooxygenase(AHH)에 의해서 생성된 반응성 대사물질들의 in vitro DNA와의 결합 및 BP 대사에 관여하는 효소들의 활성도에 미치는 인삼 물추출물의 영향을 조사하였으며, DNA-BP metabolite adduct들은 Sephadex LH-20 column으로 chromatography하여 5개의 major peak 들을 얻었다. 이 peak 들을 극성이 큰 순서대로 A부터 E까지 임의로 정하고 5개의 peak들을 7,8-diol-9,10-oxide(A), 7,8-oxide(B). 4,5-oxide(C), 9-HO-BP(D & E) adduct들로 잠정적으로 확인하였다. Peak A, C, D 그리고 E는 각각 대조군의 30, 15, 20 그리고 30%로 감소되었으며 peak B는 의미있는 변화를 보이지 않았다. DNA-BP 결합 억제와 관련하여 in vitro와 in vivo 투여시의 경향이 유사하여 EH의 활성도만 BP투여 대조군보다 38%정도 의미있게 유도되었다.

• Parasites, Hosts and Diseases
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• 제51권2호
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• pp.165-175
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• 2013

The fear that schistosomes will become resistant to praziquantel (PZQ) motivates the search for alternatives to treat schistosomiasis. The antimalarials quinine (QN) and halofantrine (HF) possess moderate antischistosomal properties. The major metabolic pathway of QN and HF is through cytochrome P450 (CYP) 3A4. Accordingly, this study investigates the effects of CYP3A4 inhibitor, ketoconazole (KTZ), on the antischistosomal potential of these quinolines against Schistosoma mansoni infection by evaluating parasitological, histopathological, and biochemical parameters. Mice were classified into 7 groups: uninfected untreated (I), infected untreated (II), infected treated orally with PZQ (1,000 mg/kg) (III), QN (400 mg/kg) (IV), KTZ (10 mg/kg)+QN as group IV (V), HF (400 mg/kg) (VI), and KTZ (as group V)+HF (as group VI) (VII). KTZ plus QN or HF produced more inhibition (P<0.05) in hepatic CYP450 (85.7% and 83.8%) and CYT b5 (75.5% and 73.5%) activities, respectively, than in groups treated with QN or HF alone. This was accompanied with more reduction in female (89.0% and 79.3%), total worms (81.4% and 70.3%), and eggs burden (hepatic; 83.8%, 66.0% and intestinal; 68%, 64.5%), respectively, and encountering the granulomatous reaction to parasite eggs trapped in the liver. QN and HF significantly (P<0.05) elevated malondialdehyde levels when used alone or with KTZ. Meanwhile, KTZ plus QN or HF restored serum levels of ALT, albumin, and reduced hepatic glutathione (KTZ+HF) to their control values. KTZ enhanced the therapeutic antischistosomal potential of QN and HF over each drug alone. Moreover, the effect of KTZ+QN was more evident than KTZ+HF.