• Title/Summary/Keyword: demethylase

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Effects of Methanol Extract from Terminalia chebulae on Renal and Pulmonary Toxicities Induced by Paraquat in Rats (가자(Terminalia chebulae) 메탄올 추출물이 paraquat 독성에 의한 흰 쥐의 신장 및 폐조직에 미치는 영향)

  • Park, Jong-Ok
    • Journal of Life Science
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    • v.18 no.1
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    • pp.129-135
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    • 2008
  • Paraquat (1,1-dimethyl 4,4' -dipyridium dichloride; PQ) is a kind of herbicide. Terminalia chebulae (TC) has been used as a medicine in China and in Korea for treating illnesses such as diarrhea, collapsed anus, spasmodic, diphtheria, asthma etc.. This study was to examin new physiological activities of methanol extract of TC (TCM) on the toxicity of PQ. It was observed biochemical effects on the toxicity of PQ in kidney and lung tissues after treatment orally administered 100, 200, 300 mg/kg of TCM daily for two weeks. In the experiment related to the toxicity of PQ, we got following results: renal and pulmonary lipid peroxide contents, activities of aminopyrine N-demethylase, aldehyde oxidase and xanthine oxidase were significantly increased in control group as compared with normal group, in the treatment of TCM the values were decreased as compared with control group. Activities of superoxide dismutase, catalase and glutathione peroxidase which are free radical scavenging enzymes were also increased in control group as compared with normal goup, but were decreased in TCM group as compared with control group. Collagen content and glucose-6-phosphatase activity in lung tissue were increased in control group as compared with normal, but was decreased in TCM group as compared with control group. From these results, we concluded that TCM can playa role as an effective agent to decrease toxicity of PQ.

The Effect of water-extract of Epimedium koreanum Nakai on age-related changes of the xenobiotic metabolizing enzyme system in the liver of rats (음양곽의 추출물이 노화에 따른 흰쥐 간의 이물질대사 효소계에 미치는 영향)

  • Lee, Young-Gu;Sohn, Hyung-Ok;Lee, Dong-Wook;Lim, Heung-Bin
    • Korean Journal of Medicinal Crop Science
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    • v.10 no.1
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    • pp.29-36
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    • 2002
  • Epimedium koreanum Nakai(EKN) has traditionally been well-known as a herbal medicine for the promotion of stamina and the improving sexual activity of human in oriental countries including Korea and China. The aim of this study was to investigate the effect of dietary supplementation of EKN water-extract(0.025%,w/v) on age-related change of xenobiotic metabolizing system in rat liver. Long-term supply of the EKN extract to rats did not induce any discernible signs. However, the mass of liver and kidney were slightly increased by the dietary supplementation. Level of cytochrome P450, NADPH cytochrome P450 reductase, P450 dependent ethoxycoumarin O-deethylase benzphetamine N-demethylase and glutathione-S-transferase in liver were decreased with age, but, these activities in 24 months of age were declined more in rats supplied with EKN extract. Level of cytochrome b5 and NADH-cytochrome b5 reductase were also decreased with age, however, there was no significant difference between with and without EKN extract. These results indicate that long-term supplementation of EKN extract to rats from weaning to 24 months may be a burden on the liver function in old age, and may aggregate the decline of xenobiotic metabolizing enzymes activities in old age.

Effects of Dandelion on Oxygen Free Radical Generating and Scavenging System of Brain in Streptozotocin-Induced Diabetic Rats (서양민들레가 Streptozotocin으로 유발한 당뇨 횐쥐의 뇌조직 중 유해 활성산소 생성 및 제거 효소계에 미치는 영향)

  • 김명주;조수열
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.3
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    • pp.500-505
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    • 2002
  • Many studies have shown that hyperglycemia leads to an increase of lipid peroxidation in diabetic patients and animals, reflecting a rise reactive oxygen species production. It is increasingly recognized that brain is another site of diabetic organ damage. Accordingly, this study was to investigate the effect of dandelion on oxygen free radical generating and scavenging system of brain in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were divided into diabetic (control) and diabetic-dandelion supplemented groups. Dandelion was supplemented for 4 weeks with dandelion leaf and root powder (DLP, DRP) or dandelion leaf and root water extract (DLW, DRW) based on 11.4 g of raw dandelion/kg diet. Diabetes was induced by single injection STZ (55 mg/kg B.W., i.p.)in a citrate buffer. Oxygen free radical generating enzymes, cytochrome P-450, amino-pyrine N-demethylase, aniline hydroxylase and xanthine oxidase, were lowered in dandelion supplemented-groups compared to the control group. Superoxide dismutase, catalase and gluthathione peroxidase activities of brain were also lower in dandelion leaf and root supplemented-group than in the control group, whereas glutathione S-transferase activity and gluthathione content were increased in dandelion supplemented-groups compared to the control group. With regard to the lipid peroxidation products, the malondialdehyde content of brain was lower in dandelion supplemented groups. Therefore, it could be suggested that powder and water extract of dandelion leaf or root are beneficial in preventing diabetic complication from lipid peroxidation and free radical in brain of diabetic rat brain.

Ethanol Prevents from Acetaminophen Inducible Hepatic Necrosis by Inhibiting its Metabolic Activation in Mice

  • Lee, Sun-Mee;Cho, Tai-Soon;Cha, Young-Nam
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.2
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    • pp.261-269
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    • 1998
  • Concomitant administration of a single acute dose of ethanol (4 g/kg) protected mice from the hepatocellular injury observed upon administration of a large dose of acetaminophen (400 mg/kg). This was evidenced by the normal histological appearances of liver sections and by the lowered serum aminotransferase activities in mice treated with ethanol and acetaminophen together. In the mice treated with acetaminophen alone, along with the hepatic necrosis, the hepatic microsomal aminopyrine N-demethylase activity was decreased. However, co-administration of ethanol prevented this acetaminophen dependent inhibition on the microsomal mixed function oxidase activity. Pharmacokinetic studies indicated that the concentration of un-metabolized drug in the blood was increased in the ethanol treated mice. Furthermore, upon co-administration of ethanol, although the biliary levels of acetaminophen metabolites (glucuronide, sulfate and cysteine conjugates) were decreased, the level of unmetabolized acetaminophen was increased. Our findings suggest that co-administration of an acute dose of ethanol reduces the degree of hepatocellular necrosis produced by a large dose of acetaminophen and this ethanol dependent protection is, in major part, afforded by suppression of the hepatic microsomal mixed function oxidase activity catalyzing the metabolic activation of acetaminophen.

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Methylated-UHRF1 and PARP1 interaction is critical for homologous recombination

  • Hahm, Ja Young;Kang, Joo-Young;Park, Jin Woo;Jung, Hyeonsoo;Seo, Sang-Beom
    • BMB Reports
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    • v.53 no.2
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    • pp.112-117
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    • 2020
  • A recent study suggested that methylation of ubiquitin-like with PHD and RING finger domain 1 (UHRF1) is regulated by SET7 and lysine-specific histone demethylase 1A (LSD1) and is essential for homologous recombination (HR). The study demonstrated that SET7-mediated methylation of UHRF1 promotes polyubiquitination of proliferating cell nuclear antigen (PCNA), inducing HR. However, studies on mediators that interact with and recruit UHRF1 to damaged lesions are needed to elucidate the mechanism of UHRF1 methylation-induced HR. Here, we identified that poly [ADP-ribose] polymerase 1 (PARP1) interacts with damage-induced methylated UHRF1 specifically and mediates UHRF1 to induce HR progression. Furthermore, cooperation of UHRF1-PARP1 is essential for cell viability, suggesting the importance of the interaction of UHRF1-PARP1 for damage tolerance in response to damage. Our data revealed that PARP1 mediates the HR mechanism, which is regulated by UHRF1 methylation. The data also indicated the significant role of PARP1 as a mediator of UHRF1 methylation-correlated HR pathway.

Effects of the Methanol Extract of the Leaves of Brassica juncea and Its Major Component, Isorhamnetin $3-O-{\beta}-D-Glucoside$, on Hepatic Drug Metabolizing Enzymes in Bromobenzene-treated Rats

  • Hur, Jong-Moon;Choi, Jong-Won;Park, Jong-Cheol
    • Food Science and Biotechnology
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    • v.16 no.3
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    • pp.439-443
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    • 2007
  • The effects of the methanol extract of the leaves of Brassica juncea and isorhamnetin $3-O-{\beta}-D-glucopyranoside$, major compound isolated from the ethyl acetate fraction of this plant on hepatic lipid peroxidation and drug-metabolizing enzymes, were evaluated in rats treated with bromobenzene. The extract and isorhamnetin $3-O-{\beta}-D-glucopyranoside$ of oral administration did not show any significant effects on activities of aminopyrine N-demethylase and aniline hydroxylase, enzymes forming toxic epoxide by bromobenzene as well as on glutathione content. However, both methanol extract and isorhamnetin $3-O-{\beta}-D-glucopyranoside$ significantly recovered the decreased activities of glutathione s-transferase and epoxide hydrolase, and also reduced the lipid peroxide level in rats treated with bromobenzene. From the results, the protections of this plant against bromobenzene-induced hepatotoxicity are thought to be via enhancing the activities of epoxide hydrolase and glutathione s-transferase, enzymes removing toxic epoxide, and reducing the lipid peroxide level.

Vitamins E and C: Are They Synergistic in Protecting Liver Cells against Hepatic Ischimia and Reperfusion Injury\ulcorner (간장내 허혈 및 재관류시 Vitamin E와 C의 간세포 보호작용)

  • 이선미;김순애;조태순
    • Biomolecules & Therapeutics
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    • v.5 no.1
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    • pp.59-66
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    • 1997
  • This study was done to determine that vitamins I and C are synergistic in protecting liver cells during hepatic ischemia and repefusion. Rats treated with vitamins I and C were subjected to 60 min of hepatic ischemia and to 1 and 5 hr of reperfusion thereafter. Serum aminotransferase level and microsomal lipid peroxidation were markedly increased by ischemia/reperfusion. These increases were significantly attenuated by vitamins E, C or its combination. Hepatic wet weight-to-dry weight ratio was increased in ischemic group, but this increase was prevented by combination of vitamin I and C. Bile flow and cholate output were markedly decreased by ischemia/reperfusion and vitamin C alone and combination of vitamin I and C restored their secretion. Cytochrome P-450 content and aminopyrine N-demethylase activity were decreased by ischemia/ reperfusion and restored by vitamin C and combination of vitamin I and C to the level of sham-operated rat. Aniline p-hydroxylase activity was increased by ischemia/reperfusion and this increase was prevented by vitamin E. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory and microsomal functions by increasing lipid peroxidation and vitamins I and C synergistically ameliorates these changes.

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Pharmacokinetic Interaction of Chrysin with Caffeine in Rats

  • Noh, Keumhan;Oh, Do Gyeong;Nepal, Mahesh Raj;Jeong, Ki Sun;Choi, Yongjoo;Kang, Mi Jeong;Kang, Wonku;Jeong, Hye Gwang;Jeong, Tae Cheon
    • Biomolecules & Therapeutics
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    • v.24 no.4
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    • pp.446-452
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    • 2016
  • Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism.

The Effect of Korean Red Ginseng Water-extract on Aging-related Changes in the Xenobiotic Metabolizing Enzyme System in the Liver of Rats (홍삼의 물추출물이 노화에 따른 흰쥐 간의 이물질대사 효소계에 미치는 영향)

  • Lee, Dong-Wook;Lim, Heung-Bin
    • Korean Journal of Medicinal Crop Science
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    • v.14 no.6
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    • pp.329-335
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    • 2006
  • The present study was designed to investigate aging-related effects on the activities of xenobiotic metabolizing enzymes of rat liver by dietary supplementation of Korean red ginseng water-extract. Rat did not show any discernible signs of the rejection symptoms, and blood GOT and GPT levels were not influenced by ginseng water extracts, Cytochrome 450 levels and NADPH cytochrome P45O reductase, p-450 dependent ethoxycoumarin O-deethylase, and benzphetamine N-demethylase activities were decreased with aging, however, these phase I system enzymes activities in the ginseng group of24 months were well maintained compared with normal group. But, Levels of cytochrome bs and NADH-cytochrome b$_5$ reductase activities were also decreased with aging and were not found a clear difference between two groups. Glutathione-s-transferase activity, phase II enzyme system, in liver cytosols was also decreased in old ages, but the degree of decrease was higher in normal group than in giuseng supplemented group. These results indicate that long-term supplementation of red ginseng water extracts from weaning to 24 months do not show any side effects to rats, and retard age-related deteriorations of xenobiotic metabolizing enzymes activities in old ages.

Correlation between microsomal lipid peroxidation levels and drug metabolizing enzymes in rats on various ages (연령증가에 따른 마이크로솜 막지질 과산화수준의 변화와 해독효소계의 관계)

  • Cho, Jong-Hoo;Hwang, DaeWoo;Park, Sang-Youel
    • Korean Journal of Veterinary Research
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    • v.43 no.4
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    • pp.579-585
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    • 2003
  • The studies were carried out on the correlation between microsomal lipid peroxidation level and drug metabolizing enzyme activities in rat liver microsomal suspensions on various ages (2-week-old, 2, 4, 8, and 12-month-old). The lipid peroxidation levels of liver homogenates tended to be elevated in a 4-month-old rat livers, but it was a little decreased in 8 and 12-month-old rat livers. The lipid peroxidation levels of microsomal suspension was not shown any significant differences by ages. Lipid peroxidation levels and microsomal cytochrome P450 and NADPH-cytochrome c reductase activity showed a direct correlation (r=0.72 and r=0.64), respectively. The activities of cytochrome P450-dependent aminopyrine-N-demethylase and benzpyrene hydroxylase in rat liver microsomes were increased by ages up to 8-month-old rats and maintained in 12-month-old rats. The correlation between lipid peroxidation levels and these cytochrome-dependent enzyme activities showed a high direct correlation (r=0.97 and r=0.81), respectively.