• Title/Summary/Keyword: Cytochrome P450 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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    • v.5 no.4
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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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    • v.24 no.1
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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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Involvement of Kupffer Cell in $CCl_4$ induced Liver Injury: The Role of Calcium (사염화 탄소에 의한 간손상에 있어 Kupffer cell 칼슘의 역할)

  • Yang, Mie-Rha
    • The Korean Journal of Pharmacology
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    • v.32 no.1
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    • pp.75-82
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    • 1996
  • The hypothesis that calcium provoke $O_2^-$ formation by Kupffer cells and may contribute to carbon tetrachloride $(CCl_4)$ induced liver injury was studied in SD rats. In $CCl_4-treated$ animals, hepatic malonaldehyde (nmole/gm liver) and plasma ALT (IU/ml) levels elevated significantly from $119.63{\pm}13.00$ to $268.97{\pm}14.82$ and from $17.3{\pm}0.18$ to $806.08{\pm}37.63$, respectively, compared to those in controls. Activation of Kupffer cells with high dose of retinol (250,000 IU/kg/day, po, for 7 day) significantly enhanced ALT levels, while inactivation of Kupffer cells with gadolinium chloride (7.5 mg/kg/day, ip, for 2 day) attenuated the increase of serum ALT level following $CCl_4$ treatment. Diltiazem (10 mg/kg/day, ip for 2 day) given in combination with retinol led to a marked decrease in ALT levels compare to the level in rats treated only with retinol against $CCl_4$ treatment. In order to determine any alterations in cytochrome P450 activities, the P450 content and the CYP2E1 activity were measured and all $CCl_4-treated$ rats showed significantly lower levels compared to those in controls and vehicle-treated animals. There were significant increases in glutathione peroxidase in all $CCl_4-treated$ rats except diltiazem treated groups. No difference was found among untreated and vehicle-treated rats. It is concluded that Kupffer cells contribute to $CCl_4-induced$ liver injury and that calcium antagonist attenuated the increased $CCl_4-induced$ liver injury due to activation of Kupffer cells.

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

  • Kim Bo-Kyung;Lee Sang-Ryong
    • Journal of Oriental Neuropsychiatry
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    • v.9 no.1
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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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    • v.31 no.3
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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.

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

  • Kim Seong-Hyeon;Lee Sang-Ryong
    • Journal of Oriental Neuropsychiatry
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    • v.8 no.2
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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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    • v.17 no.7
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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).

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

  • Jung In-Chul;Lee Sang-Ryong
    • Journal of Oriental Neuropsychiatry
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    • v.8 no.2
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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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    • v.2 no.2
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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
    • Proceedings of the PSK Conference
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    • 2003.04a
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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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