• Title/Summary/Keyword: cytochrome P450s

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Cloning and Characterization of Soybean IFS (Isoflavone Synthase) Genes from Korean Cultivar, Sinpaldalkong (신팔달콩 유래 IFS (isoflavone synthase)유전자 클로닝 및 기능 규명)

  • Park, Hayng-Mi;Shin, Sang-Hyun;Ko, Jong-Min;Yi, Gi-Hwan;Nam, Min-Hee;Chung, Young-Soo;Chung, Won-Bok;Lee, Jai-Heon;Park, Seong-Whan
    • Journal of Life Science
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    • v.14 no.1
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    • pp.38-44
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    • 2004
  • Two genes, SinIFS1 and SinIFS2 from Korean soybean cultivar, Sinpaldalkong known as one of isoflavonerich cultivars, were cloned with PCR and degenerate primers. The sequences of two genes were analyzed with previously reported IFS genes of leguminous plants and their expression pattern in various environmental conditions was surveyed. The genomic clone of SinIFS1 contained 1,828bp nucleotides and encoded a polypeptide of 521 amino acids, and 1912bp nucleotides and a polypeptide of 521 amino acids for SinIFS2. Both genes included several conserved motifs, oxygen binding and activation (A/G-G-X-E/D-T-T/S), ERR triad (E...R....R), and heme binding (F-X-X-G-X-R-X-C-X-G) domain, which are typical in any member of cytochrome P45O superfamily. Very high sequence homology (>98%) was observed in the comparison with other IFSs of legumes. In the northern blot analysis to check the expression and increase of SinIFS1 to various environmental renditions (low temperature, light, dark, UV, and fungal elicitor), the most significant induction, more than 6 times of transcript level compared to the dark treatment as a control, was observed from the fungal elicitor treatment. The next up-regulated expression was from UV treatment (4${\times}$), low temperature and light conditions.

Effect of Dandelion (Taraxacum officinale) Leaf Extracts on Hepatic Antioxidative System in Rats fed High Cholesterol Diet (고콜레스테롤 흰쥐의 간조직 항산화효소계에 미치는 민들레잎 추출물의 영향)

  • 조수열;오연진;박지윤;이미경;김명주
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.3
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    • pp.458-463
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    • 2003
  • This study was conducted to investigate the effects of dandelion leaf (Taraxacum officinale) extracts on hepatic antioxidative system in high cholesterol-fed rats. Four groups of rats were given high cholesterol diets containing 10 g cholesterol/kg and 2.5 g sodium cholate/kg for 6 weeks. The control group received a diet without dandelion leaf extract and the other three groups received dandelion leaf extracts, ie, water, ethyl acetate and ether extracts, respectively. There were no significant difference in cytochrome P-450 contents among four groups. Hepatic xanthine oxidase activity was significantly lower in water extract group than the other three groups. Superoxide dismutase activity was significantly lower in three dandelion leaf extract groups, but catalase activity was significantly higher in three dandelion leaf extract groups than control group. Glutathione peroxidase and glutathione S-transferase activities were significantly increased in water extract group than control group. Lipid peroxide content was decreased in water extract group than control group.

The Effects of Chungpyesagan-tang on the Recovery of Liver Function in Rat Injured by $CCl_4$ (청폐사간탕(淸肺瀉肝湯)이 $CCl_4$로 유발(誘發)된 휜쥐의 간손상(肝損傷)에 마치는 영향(影響))

  • Shin, Mee-Ran;Heo, Woon-Yeong;Kim, DaI-Rae;Jeon, Jong-Weon;Kim, Jeong-Yeol
    • Journal of Sasang Constitutional Medicine
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    • v.17 no.1
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    • pp.130-141
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    • 2005
  • 1. Objectives The present study was carried out to investigate the effects of Chungpyesagan-tang on the $CCI_4-induced$ Liver Damage in Rats. 2. Methods Sprague-Dawley rats were devided into 5 experimental groups : Normal, $NS+CCI_4(Solid$ extract of $CCI_4$ injection group after Normal Saline feed), $CP+CCI_4(Solid$ extract of $CCI_4$ injection group after Chungpyesagantang feed), $CCI_4+NS(Nomal$ Saline feed group after $CCI_4$ injection), $CCI_4+CP(Solid$ extract of Chungpyesagantang feed group after $CCI_4$ injection). Biochemical assays for serum enzyme activities such as AST, ALT, ALP, BUN, Creatinine, Uric Acid, Total Protein, Albumin, Total Cholesterol, Triglyceride, Glucose, and mRNA Revelation of Cytochrome p450 and activities such as LPO(Lipid Peroxidation), GSH(Glutathione), GST(Glutathione-S- Transferase), Glutathione Reductase, Glutathione Peroxidase, SOD(Superoxide Dismutase), Catalase, Hydroxyproline, and ${\beta}-Glucuronidase$ were performed. 3. Results 1) $CP+CCI_4$ showed significantly lower relation of Cytochrome p450 than $NS+CCI_4$. 2) As to LPO Hydroxyproline, $CCI_4+CP$ showed significantly lower activity than $CCI_4+NS$. 3) As to GSH GST Glutathione Peroxidase Catalase, $CP+CCI_4$ showed higher activity than $NS+CCI_4$, $CCI_4+CP$ showed significantly higher activity than $CCI_4+NS$. 4) As to Glutathione Reductase SOD, $CCI_4+CP$ showed significantly higher activity than $CCI_4+NS$. 5) As to ${\beta}-Glucuronidase$, $CP+CCI_4$ showed signficantly lower activity than $NS+CCI_4$. 4. Conclusions Chungpyesagantang has the recovering effects on the $CCI_4-induced$ Liver Damage.

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Antigenotoxicity of Vegetable or Fruit Extract against Cigarette Smoke Condensate (담배연기응축물의 DNA 손상작용과 야채 및 과일추출물의 보호효과)

  • Lee, Hyeong-Ju;Heo, Chan;Kim, Nam-Yee;Heo, Moon-Young
    • YAKHAK HOEJI
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    • v.55 no.3
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    • pp.251-259
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    • 2011
  • Cigarette smoke condensate (CSC) is known to be carcinogenic compound. CSC contains many organic compounds such as polycyclic aromatic hydrocarbons (PAHs), and heterocyclic amine compounds (HCAs). Reactive oxygen species (ROS) are also generated and induce oxidative DNA damage during the metabolism of CSC. The rat microsome mediated and DNA repair enzyme treated comet assays together with conventional comet assay were performed to evaluate the mechanisms of CSC genotoxicity. The organic extract of CSC induced oxidative and microsome mediated DNA damage. Vitamin C as a model antioxidant reduced DNA damage in endonuclease III treated comet assay. One of flavonoid, galangin as a CYP1A1 inhibitor, reduced DNA damage in the presence of S-9 mixture. The ethanol extracts of the mixed vegetables (BV) or the mixed fruits (BF) showed potent inhibitory effects against CSC induced DNA damage with oxidative DNA lesions and in the prescence of S-9 mixture. These results indicate that BV and BF could prevent CSC-induced cellular DNA damage by inhibiting oxidative stress and suppressing cytochrome P450 in mammalian cells.

Dosage Adjustment before and after Warfarin - Rifampin Combination Therapy (와파린-리팜핀 병용 시 용량 조절)

  • Kim, Dong-Hyun;Kim, Kyung-Hwan;Choi, Kyung-Hee;Lee, Kwang-Ja;Lee, Hye-Suk;Son, In-Ja;Kim, Ki-Bong;Lee, Jae-Woong;Ahn, Hyuk
    • Journal of Chest Surgery
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    • v.41 no.3
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    • pp.354-359
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    • 2008
  • Background: Warfarin is used as an anticoagulant and it is mainly excreted by the liver metabolism (the R-form is mainly metabolized by cytochrome p450 3A4, and the S form by cytochrome p450 2C9). Rifampin is usually used for tuberculosis or endocarditis, and it is a representative drug that induces the CYP families, including 3A4 and 2C9. The anticoagulation effect of warfarin decreases through the increased metabolism that's due to the induction of enzymes, and this iscaused by rifampin when patients take these two medicines together. No one has suggested appropriate guidelines regarding this drug interaction even though an appropriate adjustment of warfarin's dosage is needed. We examined the drug interaction in patients who received warfarin-rifampin combination therapy according to the time interval, and the factors affecting drug interaction were analyzed. Based on the data, we tried to determine the clinically available warfarin dosage guidelines before and after taking this drug combination. Material and Method: We reviewed the OO University Hospital anticoagulation service team's follow up sheets that were filled out from Jan '1998 to Sep 2006 for the patient who took warfarin - rifampin combination therapy (n=15). Result: The average INR of all the patient before rifampin administration was $2.25{\pm}0.52$ $(mean{\pm}SD)$, and that value for the first 100 days after rifampin administration was $1.98{\pm}0.28$. The p value for these two sets of data showed no correlation (paired t-test, p>0.05). The average INR of all the patient before rifampin cessation was $2.19{\pm}0.34$, and the value after rifampin cessation was $2.49{\pm}0.43$. The p value of these two showed correlation (paired t-test, p<0.05) but the average INR falls between the therapeutic INR range. Conclusion: The warfarin dose adjustment equation of before and after warfarin-rifampin combination therapy was derived based on this study's results because the warfarin dosage adjustment of the anticoagulation service team was considered appropriate.

Reduction of Bacterial Mutagenesis of 2-Amino-3-Methylimidazo[4,5-f]quinoline by S-9 Fraction from Mice Treated with Conjugated Linoleic Acid (CLA)

  • Park, Kyung-Ah;Kim, Seck-Jong;Park, Soo-Jahr;Park, Gu-Boo;Lim, Dong-Kil;Bahn, Kyeong-Nyeo;Cho, Yong-Un;Park, Jung H.Y.;Pariza, Michael W.;Ha, Yeongl-Lae
    • Preventive Nutrition and Food Science
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    • v.6 no.1
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    • pp.57-61
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    • 2001
  • Conjugated linoleic acid (CLA), when incorporated into mouse liver microsomal membranes, selectively inhibits the mutagenesis of 2-amino-3-methylimidazo[4,5-f] quinoline (IQ). Nine-week old female ICR mice were given (p.o.) 0.1 mL olive oil alone (control), 0.1 mL olive oil plus 0.1 mL linoleic acid, or 0.1 mL olive oil plus 0.1 mL CLA, twice weekly for four weeks. The animals were then sacrificed and liver S-9 fractions were prepared. Activation of IQ for mutagenesis by the liver S-9 from CLA-treated mice was significantly reduced in comparison wit liver S-9 from control or linolic acid-treated mice. By contrast, the activation of 7,12-dimethylbenz[a] anthracene (DMBA) and benzo[a] pyrene (BP) was unaffected. Hence, CLA incorporated into phospholipids may selectively affect cytochrome P450 isozymes responsible for activating IQ, but not those which activate BP or DMBA. The addition of free CLA or the methyl esters of CLA, linoleic acid, or oleic acid, to control S-9 inhibited the activation of all three mutagens (IQ, BP, and DMBA).

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Expression of CYP1A1 and GSTP1 in Human Brain Tumor Tissues in Pakistan

  • Wahid, Mussarat;Mahjabeen, Ishrat;Baig, Ruqia Mehmood;Kayani, Mahmood Akhtar
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7187-7191
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    • 2013
  • Most of the exogenous and endogenous chemical compounds are metabolized by enzymes of xenobiotic processing pathways, including the phase I cytochrome p450 species. Carcinogens and their metabolites are generally detoxified by phase II enzymes like glutathione-S-transferases (GST). The balance of enzymes determines whether metabolic activation of pro-carcinogens or inactivation of carcinogens occurs. Under certain conditions, deregulated expression of xenobiotic enzymes may also convert endogenous substrates to metabolites that can facilitate DNA adduct formation and ultimately lead to cancer development. In this study, we aimed to test the association between deregulation of metabolizing genes and brain tumorigenesis. The expression profile of metabolizing genes CYP1A1 and GSTP1 was therefore studied in a cohort of 36 brain tumor patients and controls using Western blotting. In a second part of the study we analyzed protein expression of GSTs in the same study cohort by ELISA. CYP1A1 expression was found to be significantly high (p<0.001) in brain tumor as compared to the normal tissues, with ~4 fold (OR=4, 95%CI=0.43-37) increase in some cases. In contrast, the expression of GSTP1 was found to be significantly low in brain tumor tissues as compared to the controls (p<0.02). This down regulation was significantly higher (OR=0.05, 95%CI=0.006-0.51; p<0.007) in certain grades of lesions. Furthermore, GSTs levels were significantly down-regulated (p<0.014) in brain tumor patients compared to controls. Statistically significant decrease in GST levels was observed in the more advanced lesions (III-IV, p<0.005) as compared to the early tissue grades (I-II). Thus, altered expression of these xenobiotic metabolizing genes may be involved in brain tumor development in Pakistani population. Investigation of expression of these genes may provide information not only for the prediction of individual cancer risk but also for the prevention of cancer.

Effects of Rubi Fructus Water Extract On Oxygen Free Radical Metabolizing Enzyme Activites (복분자가 유리산소 대사효소 활성에 미치는 영향)

  • Lee Kwang Gyu;Cui Xun;Lim Jong Pil
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.5
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    • pp.911-913
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    • 2002
  • Rubi Fructus (fruit of Rubus coreanus Miq.), oriental medicine, has been used for remedy of the liver diseases and for tonic. In order to investigate the oxygen free radical, a harmful factor of aging, in liver of rats fed diets supplemented with the Rubi Fructus water extract(RX), Sprague-Dawley male rats have been fed a diet supplemented with 3% or 5% RX for a month. In rats fed 3% RX supplemented diet, hepatic cytochrome P-450 contents appeared to be increased, and catalase and superoxide dismutase activities were significantly increased compared with the control. There was no difference in glutathione peroxide and glutathione-S-transferase activities between the rats fed RX supplemented diets and the control diet. In conclusion, it is likely that rats fed a diet supplemented with RX may have the oxygen free radicals detoxication potential.

Effects of Godulbaegi(Ixeris Sonchifolia H.) Diets on Enzyme Activities of CCI4 Induced Hepatotoxicity in Rats (고들빼기 식이가 간 독성을 유발한 흰쥐의 효소 활성에 미치는 영향)

  • 배송자
    • Journal of Nutrition and Health
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    • v.30 no.1
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    • pp.19-24
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    • 1997
  • This study was carried out to investigate the effects of enzyme activities on male Sprague-Dawley rats intoxicated by CCI4 on IS(Godulbaegi) diets for 4 weeks. We divides into 5 diet groups which were normal diet(N), normal diet intoxicated by CCI4(NC) and 3 IS diets ; leaves diet(ILC), roots diet(IRC) and mixed diet of leaves and roots which were also injected by CCI4 3 times for 4 weeks. The activity of glutamic pyruvic transaminase(GPT) in serum in NC was higher than in N as we expected. The GPT activites and the values of malondial-dehyde(MDA) of IS groups were all lower than in NC, IC as lowest. The activity of superoxide dismutase(SOD) in NC was higher than in N and IS groups had values less than the values of N. Catalase showed similarity in results as above. The values of glutathione S-transferase(GST) and cytochrome P-450 in NC were lower than in N. IS groups had higher values than in NC. Godulbaegi might be important not only as one of the traditional Korean foods but also as therapeutic agent for hepatotoxicity and for shortening the recovery time in liver disease.

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Tacrolimus versus Cyclosporine Immunosuppression in Pediatric Renal Transplantation : Pharmacokinetic Consideration (신장 이식에 사용되는 주요 면역억제제와 약물 동력학 검사)

  • Kim, Jung Sue
    • Clinical and Experimental Pediatrics
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    • v.48 no.5
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    • pp.476-480
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    • 2005
  • Immunosuppressive therapy in pediatric renal transplant recipients is changing consequence of the increasing number of available immunosuppressive agents. The optimal use of immunosuppressive agents requires a thorough understanding of the pharmacokinetic characteristics, but the information on the pharmacokinetic characteristics of these drugs in pediatric transplant recipients is still limited. In general, patients younger than 5 years old show higher clearance rates, therefore the need for higher dosages in younger patients seems evident. By the therapeutic drug monitoring, trough($C_{min}$) and peak level($C_{max}$) are measured and the area under the blood concentration-time curve(AUC), which is taken as being representative of total systemic exposure can be calculated. Cyclosporine A (CSA) has poor bioavailability, which contributes to high inter- and intra-patient pharmacokinetic variability. CSA concentration measured 2 hours after administration($C_2$) has better correlation with the AUC than $C_{min}$ and is an alternative technique that predicts the AUC. Tacrolimus(Tac) has a great deal of inter-individual variability like CSA but intra-individual variability in systemic exposure is considered to be low. Both CSA and Tac are metabolized by a cytochrome P-450 enzyme isoform(CYP3A4). We should consider changing the dosages when CSA or Tac is used in combination with the medicines that inhibit or induce the CYP3A4. In case of steroid-free immunosuppressive therapy, the blood concentration of Tac should be frequently checked and dosage adjustment may be needed.