• Title/Summary/Keyword: cytochrome P-450 2E1

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Effects of Green Tea Catechin on Platelet Phospholipase $A_{2}$ Activity and the Liver Antioxidative Defense System in Streptozotocin-induced Diabetic Rats

  • Yang, Jeong-Ah;Rhee, Soon-Jae
    • Preventive Nutrition and Food Science
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    • 제5권4호
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    • pp.213-218
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    • 2000
  • The purpose of the study was to investigate the effects of dietary green tea catechin and vitamin E on the phospholipse {TEX}$A_{2}${/TEX} activity and th antioxidative defense system in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley male rats weighing 100$\pm$10 gm were randomly assigned to one normal and five STZ-induced diabetic groups. The diabetic groups were assigned either a catechin-free diet (DM group), 0.5% catechin diet (DM-0.5C group), 1% catechin diet (DM-1C group), vitamin E-free diet (DM-0E group), and 400 mg vitamin E per kg diet (DM-400E group) according to the levels of dietary catechin or vitamin E supplementation. The vitamin E levels of the normal, DM, DM-0.5C, and DM-1C groups were 40 mg per kg diet. Diabetes was experimentally induced by an intravenous injection of streptozotocin after 4 weeks of feeding the five experimental diets. The animals were sacrificed on the 6th day of he diabetic state. The body weight gains were lower in all five diabetic groups after the STZ injection. The platelet phospholipase {TEX}$A_{2}${/TEX}({TEX}$PLA_{2}${/TEX}) activity in the diabetic groups was higher than that in the normal group. However, the enzyme activity in the DM-0.5C, DM-1C, and DM-400E groups was lower than that in the DM and DM-0E groups. The cytochrome {TEX}$P_{450}${/TEX} and cytochrome {TEX}$b_{5}${/TEX} content and NADPH-cytochrome {TEX}$P_{450}${/TEX} reductase activity were about 50~110% higher in the DM and DM-0E groups than in the normal group, yet significantly reduced by either catechin or vitamin E supplementation. The superoxide dismutase (SOD) content in the liver did not differ significantly in any of the groups. However, the glutathione peroxidase (GSHpx) activity was generally lower in the diabetic groups, compared with the normal group, whereas that of the DM-0.5C, DM-1C, and DM-400E groups was significantly higher compared with that of the DM and DM-0E groups. The levels of thiobarbituric acid reactive substances (TBARS) in the liver tissue were 148% and 201% higher in the DM and DM-0E groups, respectively, compared with the normal group, however, these levels were reduced by either catechin or vitamin E supplementation (DM-0.5, DM-1C and DM-400E). Accordingly, the present results indicate that STZ-induced diabetic rats exhibited an imbalance between free radical generation and scavenger systems in the liver which led to the acceleration of lipid peroxidation. However, these abnormalities were reduced and the antioxidative defense system was restored by either dietary catechin or vitamin E supplementation. In conclusion, the effects of dietary catechin or vitamin E in streptozotocin-induced diabetic rats would appear to inhibit lipid peroxidation as an anti-oxidant by regulating the activity of {TEX}$PLA_{2}${/TEX}.

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Synthesis of 2-(Allylthio)pyrazines As a Novel Cancer Chemopreventive Agent

  • Lee, Jong-Wook;Lee, Bong-yong;Kim, Nak-Doo
    • Archives of Pharmacal Research
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    • 제24권1호
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    • pp.16-20
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    • 2001
  • 2-(Allylthio)pyrazine derivatives were designed as a novel cancer chemopreventive agent that functions through selective inhibtion of cytochrome P-450 and induction of phase 11 enzymes involved in the detoxification of carcinogens. A practical preparation method of 2-(allylthio) pyrazine derivatives was established by the reaction of 2-mercaptopyrazine and allylbromides in the presence of a catalytic antioxidant, DABCO (1,4-diazabicyclo[2,2,2] octane), in dimethyl-formamide at below $50^{\circ}C$.

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사염화 탄소에 의한 간손상에 있어 Kupffer cell 칼슘의 역할 (Involvement of Kupffer Cell in $CCl_4$ induced Liver Injury: The Role of Calcium)

  • 양미라
    • 대한약리학회지
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    • 제32권1호
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    • pp.75-82
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    • 1996
  • 사염화 탄소에 의한 과산화 지질 증가 및 간 손상에 calcium 및 Kupffer cell의 역할 및 calcium channel blocker의 간 손상에 대한 방어 효과를 연구하였다. 사염화 탄소는 (1 gm/kg, ig) 간의 malondialdehyde (nmole/gm liver) 및 혈중 AST와 ALT (lU/ml) 활성도의 현저한 증가를 나타내었다. 고 농도의 Retinol (250,000U/kg/day)로 인한 Kupffer cell의 활성 증가는 사염화 탄소에 의한 간 과산화 지질 증가 및 간 손상에 상승 작용을 나타낸 반면, $GdCl_3$ 전처리는 $CCl_4$로 인한 ALT의 증가를 감소시켰다. 한편 Retinol 처치군에 Diltiazem (10mg/kg/day)을 병행하여 처치한 결과, 사염화 탄소에 의한 혈중 AST 및 ALT의 증가를 Retinol 단독 처치군에 비하여 현저하게 억제시킬 수 있었다. 이 결과들이 Retinol 혹은 Diltiazem의 투여에 의한 사염화 탄소가 cytochrome P450에 의한 대사 활성 또는 GSH와 관련된 항산화 기전에 미치는 영향에 기인한 것인가를 규명하기 위하여 cytochrome P450, cytochrome P4502El 활성도, GSH reductase 및 GSH peroxidase 활성도를 측정하였다. 그 결과, Retinol 및 Diltiazem의 전처리는 이들 효소의 활성도에 미치는 영향은 대조군에 비하여 유의한 차이가 없었다. 이상의 실험 결과를 종합하여 보면, 사염화 탄소의 투여에 의한 간 손상은 세포내 calcium의 증가를 가져오며, 이는 이차적으로 Kupffer cell을 활성화 시켜 이미 손상된 간세포의 독성을 증가시켰으며, calcium channel blocker인 Diltiazem의 투여는 사염화 탄소의 간독성을 현저하게 감소시키는 효과를 나타내었다.

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삼용지황탕(蔘茸地黃湯)이 뇌조직(腦組織)의 산화작용(酸化作用)에 미치는 영향(影響) (The Antioxidant Effects of SAMYONGJIHWANGTANG on the Brain tissue of aged rat)

  • 김보경;이상용
    • 동의신경정신과학회지
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    • 제9궈1호
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    • pp.59-71
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    • 1998
  • The effect of Samyonjihwangtang(SJT) on th level of brain antioxidants was examined in aged rat. Samyongjihwangtang(SJT) is assed Cervi Pantiri-chum Cornu, Ginseng Radix to Yukmijihwangtang. The experimental groups were divided into three groups and treated as follows ; normal group(NC), Vt.E administrated group(PC), SJT administrated Group(SJT). From the purified microsome of brain tissue, those were measures the amounts of oxidant materials like malonaldehyde(MDA) and H_2O_2, then activities of antioxidants enxymes like Superoxide dismutase, Catalase, NADPH-cytochrome P-450 reductase.The results were as follows;1. In TBA reaction to measure the amount of MDA, oxidant material of brain tissue of aged rat, both treated groups showed significant decrease.2. In the formation of Hydrogen peroxide, the treated group(SJT) showed a little decrease.3. The activity of Superoxide dismutase was increased significantly in both treated groups than normal group.4. the activity of Catalase was increased significantly in both treated groups than normal group. 5. The activity of NADPH-cytochrome P-450 reductase in the treated group(SJT) showed a little increase.According to the above results, it is suggested that Samyongjihwangtag(SJT) has some antioxidant effects on the tissue of brain.

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ALDH and CYP2E1 Single Nucleotide Polymorphism Distribution in Korean

  • Han, Dong-Hoon;Kim, Jeong-Hee
    • International Journal of Oral Biology
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    • 제31권3호
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    • pp.107-112
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    • 2006
  • Aldehyde dehydrogenase (ALDH) plays an important role in alcohol metabolism; ALDH is responsible for the oxidation of acetaldehyde generated during alcohol oxidation. ALDH is also known to oxidize various other endogenous and exogenous aldehydes. Cytochrome P-450 2E1 (CYP2E1), a liver microsomal enzyme, also metabolizes acetaldehyde and ethanol and can be induced by other inducers including acetone and ethanol. We examined single nucleotide polymorphisms (SNP) of ALDH and CYP2E1 genotypes in Korean. Restriction fragment length polymorphism (RFLP) method was used to determine ALDH and CYP2E1 SNP. Mutation in ALDH was 60% (heterozygote 46.7% and homozygote 13.3%) among 15 cases. CYP2E1 mutation was 52.7% (heterozygote 47.4% and homozygote 5.3%) among 19 cases.

세심탕(洗心湯)이 뇌조직(腦組織)의 산화작용(酸化作用)에 미치는 영향(影響) (The Antioxidant Effects of Sesimting on the Brain Tissue of Rat)

  • 김성현;이상룡
    • 동의신경정신과학회지
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    • 제8권2호
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    • pp.39-50
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    • 1997
  • This experiment was to investigate the antioxidant effect of Sesimtang(SST) on brain tissues of mouse. The experimental groups were divided into three groups and treated ad follows for 15 days ; Normal group(NC), Vt.E admistrated group(PC), SST administrated Group(SST). After the extracting microsome from brain of mouse, those were measured the amounts of oxidant materials like MDA(malonaldehyde) and $H_2O_2$, then activities of antioxidant enzymes like SOD(superoxide dismutase), catalase, NADPH-cytochrome P-450 reductase. The results were as follows; 1. In TBA reaction to measure the amount of MDA, oxidant material of brain tissue of aged rat, both treated groups showed significant decrease. 2. Hydrogen peroxide formation was showed significant decrease in both treated groups than normal group. 3. Superoxide dismutase activity was increased in both treated groups than normal group, and showed little change in SST administrated group than normal group. 4. Catalase activity was increased in both treated groups than normal group. 5. NADPH-cytochrome P-450 reductase activity was increased in both treated groups than normal group.

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Tetra Primer ARMS PCR Optimization to Detect Single Nucleotide Polymorphisms of the CYP2E1 Gene

  • Suhda, Saihas;Paramita, Dewi Kartikawati;Fachiroh, Jajah
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권7호
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    • pp.3065-3069
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    • 2016
  • Single nucleotide polymorphism (SNP) detection has been used extensively for genetic association studies of diseases including cancer. For mass, yet accurate and more economic SNP detection we have optimized tetra primer amplification refractory mutation system polymerase chain reaction (ARMS PCR) to detect three SNPs in the cytochrome P450 2E1 (CYP2E1) gene locus; i.e. rs3813865, rs2070672 and rs3813867. The optimization system strategies used were (1) designing inner and outer primers; (2) determining of their optimum primer concentration ratios; and (3) determining of the optimum PCR annealing temperature. The tetra primer ARMS PCR result could be directly observed using agarose gel electrophoresis. The method succesfully determined three SNPs in CYP2E1 locus, the results being consistent with validation using DNA sequencing and restriction fragment length polymorphisms (RFLP).

온담탕(溫膽湯)이 뇌조직(腦組織)의 산화작용(酸化作用)에 미치는 영향(影響) (The Antioxidant Effects of ONDAMTANG on the Brain Tissue of Mouse)

  • 정인철;이상룡
    • 동의신경정신과학회지
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    • 제8권2호
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    • pp.51-62
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    • 1997
  • This experiment was done to investigate the antioxidant effect of Ondamtang(ODT) on brain tissues of rats. The experimental groups were divided into three groups and treated as follows for a fifteen days ; Negative control group(NC), Vitamin E admistrated group(PC), ODT administrated Group(ODT). After the extracting microsome from brain of rats, those were measured the amounts of Malondiadehyde and Hydrogen peroxide, then activities of antioxidant enzymes like Superoxide dismutase, Catalase and NADPH-cytochrome P-450 reductadse. The results were as follows; 1. In TBA reaction to measure the amount of MDA, oxidant material of brain tissue of rats, the group treated by ODT showed significant decrease. 2. In the formation of Hydrogen peroxide, the group treated by ODT showed no change in comparison with normal group. 3. The activity of SOD in the group treated by ODT showed a little increase in comparison with normal group. 4. The activity of Catalase was increased significantly in the group treated by ODT than normal group. 5. The activity of NADPH-cytochrome P-450 reductase in the group treated by ODT showed a little increase in comparison with normal group. According to the above results, it is suggested that Ondamtang(ODT) has some antioxidant effects on tissues of brain.

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Dehydroepiandrosterone supplement increases malate dehydrogenase activity and decreases NADPH-dependent antioxidant enzyme activity in rat hepatocellular carcinogenesis

  • Kim, Jee-Won;Kim, Sook-Hee;Choi, Hay-Mie
    • Nutrition Research and Practice
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    • 제2권2호
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    • pp.80-84
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    • 2008
  • Beneficial effects of dehydroepiandrosterone (DHEA) supplement on age-associated chronic diseases such as cancer, cardiovascular disease, insulin resistance and diabetes, have been reported. However, its mechanism of action in hepatocellular carcinoma in vivo has not been investigated in detail. We have previously shown that during hepatocellular carcinogenesis, DHEA treatment decreases formation of preneoplastic glutathione S-transferase placental form-positive foci in the liver and has antioxidant effects. Here we aimed to determine the mechanism of actions of DHEA, in comparison to vitamin E, in a chemically-induced hepatocellular carcinoma model in rats. Sprague-Dawley rats were administered with control diet without a carcinogen, diets with 1.5% vitamin E, 0.5% DHEA and both of the compounds with a carcinogen for 6 weeks. The doses were previously reported to have anti-cancer effects in animals without known toxicities. With DHEA treatment, cytosolic malate dehydrogenase activities were significantly increased by ${\sim}5$ fold and glucose 6-phosphate dehydrogenase activities were decreased by ${\sim}25%$ compared to carcinogen treated group. Activities of Se-glutathione peroxidase in the cytotol was decreased siguificantly with DHEA treatment, confirming its antioxidative effect. However, liver microsomal cytochrome P-450 content and NADPH-dependent cytochrome P-450 reductase activities were not altered with DHEA treatment. Vitamin E treatment decreased cytosolic Se-glutathione peroxidase activities in accordance with our previous reports. However, vitamin E did not alter glucose 6-phosphate dehydrogenase or malate dehydrogenase activities. Our results suggest that DHEA may have decreased tumor nodule formation and reduced lipid peroxidation as previously reported, possibly by increasing the production of NADPH, a reducing equivalent for NADPH-dependent antioxidant enzymes. DHEA treatment tended to reduce glucose 6-phosphate dehydrogenase activities, which may have resulted in limited supply for de novo synthesis of DNA via inhibiting the hexose monophophaste pathway. Although both DHEA and vitamin E effectively reduced preneoplastic foci in this model, they seemed to fimction in different mechanisms. In conclusion, DHEA may be used to reduce hepatocellular carcinoma growth by targeting NADPH synthesis, cell proliferation and anti-oxidant enzyme activities during tumor growth.

Effects of Glucose Supplementation on the Pharmacokinetics of Intravenous Chlorzoxazone in Rats with Water Deprivation for 72 Hours

  • Kim, Yu-Chul;Kim, Eun-Jung;Lee, In-Chul;Kim, Sang-Geon;Lee, Myung-Gull;Kim, So-Hee
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.308.2-309
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    • 2003
  • In rats with water deprivation for 72 h (rats with dehydration), hepatic cytochrome P450 2E1 (CYP2E1) was 3-fold induced with an increase in mRNA, and glucose supplementation instead of food during 72-h water deprivation inhibited the CYP2E1 induction. Chlorzoxazone (CZX) is metabolized to 6-hydroxychlorzoxazone (OH-CZX) mainly by CYP2E1 in rats. (omitted)

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