• Title/Summary/Keyword: phase II enzyme

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Luteolin and luteolin-7-O-glucoside protect against acute liver injury through regulation of inflammatory mediators and antioxidative enzymes in GalN/LPS-induced hepatitic ICR mice

  • Park, Chung Mu;Song, Young-Sun
    • Nutrition Research and Practice
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    • v.13 no.6
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    • pp.473-479
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    • 2019
  • BACKGROUND/OBJECTIVES: Anti-inflammatory and antioxidative activities of luteolin and luteolin-7-O-glucoside were compared in galactosamine (GalN)/lipopolysaccharide (LPS)-induced hepatitic ICR mice. MATERIALS/METHODS: Male ICR mice (6 weeks old) were divided into 4 groups: normal control, GalN/LPS, luteolin, and luteolin-7-O-glucoside groups. The latter two groups were administered luteolin or luteolin-7-O-glucoside (50 mg/kg BW) daily by gavage for 3 weeks after which hepatitis was induced by intraperitoneal injection of GalN and LPS (1 g/kg BW and $10{\mu}g/kg\;BW$, respectively). RESULTS: GalN/LPS produced acute hepatic injury by a sharp increase in serum AST, ALT, and $TNF-{\alpha}$ levels, increases that were ameliorated in the experimental groups. In addition, markedly increased expressions of cyclooxygenase (COX)-2 and its transcription factors, nuclear factor $(NF)-{\kappa}B$ and activator protein (AP)-1, were also significantly attenuated in the experimental groups. Compared to luteolin-7-O-glucoside, luteolin more potently ameliorated the levels of inflammatory mediators. Phase II enzymes levels and NF-E2 p45-related factor (Nrf)-2 activation that were decreased by GalN/LPS were increased by luteolin and luteolin-7-O-glucoside administration. In addition, compared to luteolin, luteolin-7-O-glucoside acted as a more potent inducer of changes in phase II enzymes. Liver histopathology results were consistent with the mediator and enzyme results. CONCLUSION: Luteolin and luteolin-7-O-glucoside protect against GalN/LPS-induced hepatotoxicity through the regulation of inflammatory mediators and phase II enzymes.

Effects of Phytase and Carbohydrases Supplementation to Diet with a Partial Replacement of Soybean Meal with Rapeseed Meal and Cottonseed Meal on Growth Performance and Nutrient Digestibility of Growing Pigs

  • Shim, Y.H.;Chae, B.J.;Lee, J.H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.16 no.9
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    • pp.1339-1347
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    • 2003
  • An experiment was conducted to investigate the effects of microbial phytase ($Natuphos^{(R)}$) supplementation in combination with carbohydrases (composed of enzymes targeted to soybean meal (SBM) dietary components such as $\alpha$-galactosides and galactomannans; $Endo-Power^{(R)}$) to corn-soybean meal based diet (CSD) and complex diet (CD) with a partial replacement of SBM with rape seed meal (RSM) and cotton seed meal (CSM) on growth performance and nutrient digestibility of growing pigs. A total of 168 growing pigs averaging $13.18{\pm}1.77kg$ of initial body weight was arranged as a $2{\times}2$ factorial design with main effects of diet types (corn-SBM based diet (CSD) and complex diets (CD; 5% of SBM was replaced with 2.5% of RSM and 2.5% of CSM in diet for phase I (0 to 3 weeks) and 6% of SBM was replaced with 3% of RSM and 3% of CSM in diet for phase II (4 to 7 weeks))) and enzyme supplementation (none and 0.1% of phytase (500 FTU/kg diet) and 0.1% of carbohydrases). The diet with enzyme application were formulated to have a 0.18% unit lower aP than diets without enzyme application. Each treatment had three replicates with 14 pigs per replicate. To determine supplementation effect of phytase and carbohydrases on ileal amino acid digestibility of SBM, RSM and CSM, a total of 18 T-cannulated pigs (initial body weight; $13.52{\pm}1.24kg$) were assigned to six dietary treatments in the present study. Dietary treatments in metabolic trial included 1) SBM diet, 2) SBM diet+with enzymes (phytase (500 FTU/kg) and carbohydrases at 0.1%, respectively), 3) CSM diet, 4) CSM diet+enzymes, 5) RSM diet and 6) RSM diet+enzymes. During whole experimental period (0 to 7 wks), there was no difference in growth performance between diets (CSD and CD). However, dietary phytase and carbohydrases supplementation significantly improved gain/feed ratio (G:F) of growing pigs. During the phase II (4-7 weeks), dietary phytase and carbohydrases supplementation significantly improved all fecal nutrient digestibilities (Dry matter (DM), gross energy (GE), crude protein (CP), crude fat (CF), calcium (Ca) and phosphorus (P)). Dietary phytase and carbohydrases supplementation improved significantly overall ileal amino acid digestibilities of SBM, RSM and CSM based diets (p<0.05). The simultaneous inclusion of phytase and carbohydrases in both of CSD and CD reduced feed cost per kg body weight gain (FCG). Also, results suggest that 2.5 to 3% of RSM and CSM, respectively, might be used as a protein source in growing pig diets without having an adverse effect on the growth performance and nutrient digestibility and simultaneous phytase and carbohydrases addition improves nutritional value of SBM, RSM and CSM by improving ileal amino acid digestibilities.

Biosynthesis of Unnatural Phospholipids by Phospholipase D: II. Effect of Organic Solvents on Transphosphatidylation (PhosBholipase D에 의한 비천연 인지방질의 합성: IIl 포스타티딜기 전이반응에 미치는 유기용매의 효과)

  • 정의호;이해익이상영
    • KSBB Journal
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    • v.6 no.3
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    • pp.281-288
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    • 1991
  • This research was carried to investigate the effects of several organic solvents on the enzymatic transphosphatidylation in emulsion and two-phase solvent systems. The solvents having a similar dielectric constant with diethylether were effective for the enzyme activity. Diethylether and butylacetate were the most effective solvents, when added 12-15%(v/v) and 10-40%(v/v), respectively, for the synthesis of phosphatidylglycerol, phosphatidylethyleneglycol and phosphatidylpropyleneglycol. In the emulsion system, the size of ovolecithin liposome was increased and the clearness of the phospholipid bilayer was reduced as increasing the diethylether concentration. In the twophase solvent system, the rapidest reaction was obtained when water-organic solvent ratio was close to 1. The ratio of aqueous phase. however, should be lowered to 37% to gain the sole product of transphosphatidy1ation, without phosphatidohydrolysis.

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The Protective Effects of Curcuma longa Linn. Extract on Carbon Tetrachloride-Induced Hepatotoxicity in Rats via Upregulation of Nrf2

  • Lee, Hyeong-Seon;Li, Li;Kim, Hyun-Kyung;Bilehal, Dinesh;Li, Wei;Lee, Dong-Seok;Kim, Yong-Ho
    • Journal of Microbiology and Biotechnology
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    • v.20 no.9
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    • pp.1331-1338
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    • 2010
  • This study was designed to investigate the potentially protective effects of Curcuma longa Linn. extract (CLE) on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity in rats. Male Sprague-Dawley rats were pretreated with 50 or 100mg/kg of CLE or 100mg/kg of butylated hydroxytoluene(BHT) for 14 days before $CCl_4$ administration. In addition, the CLE control group was pretreated with 100mg/kg CLE for only 14 days. Three hours after the final treatment, a single dose of $CCl_4$ (20mg/kg) was administrated intraperitoneally to each group. After the completion of this phase of the experiment, food and water were removed 12 h prior to the next step. The rats were then anesthetized by urethane and their blood and liver were collected. It was observed that the aspartate aminotransferase and alanine aminotransferase activities of the serum, and the hepatic malondialdehyde levels had significantly decreased in the CLE group when compared with the $CCl_4$-treated group. The antioxidant activities, such as superoxide dismutase, catalase, and glutathione peroxidase activities, in addition to glutathione content, had increased considerably in the CLE group compared with the $CCl_4$-treated group. Phase II detoxifying enzymes, such as glutathione S-transferase, were found to have significantly increased in the CLE group as opposed to the $CCl_4$-treated group. The content of Nrf2 was determined by Western blot analysis. Pretreated CLE increased the level of nuclear translocated Nrf2, and the Nrf2 then increased the activity of the antioxidant and phase II detoxifying enzymes. These results indicate that CLE has protective effects against $CCl_4$-induced hepatotoxicity in rats, via activities of antioxidant and phase II detoxifying enzymes, and through the activation of nuclear translocated Nrf2.

Protective Effect of DWP-04 Against Hepatotoxicity Induced by D-galactosamine (흰쥐에서 DWP-04가 D-galactosamine에 의해 유도된 간독성의 보호효과)

  • Lee Jung-Hee;Chi Sang Cheol;Kim Seok-Hwan;Shin Young-Ho;Choi Jongwon
    • Journal of Life Science
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    • v.15 no.3 s.70
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    • pp.461-467
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    • 2005
  • This study was conducted to investigate the biological activity and hepatoprotective effect of DWP-04 [DDB : selenium yeast: glutathione (31.1 : 6.8 : 62.1(w/w/w)] in D-galactosamine (GaIN) intoxicated rats. The DWP-04 (50, 100 or 200 mg/kg) or its vehicle was orally administered everyday before the start of GaIN injection (400 mg/kg, ip) for two weeks and animal decapitated for 24 hrs after GaIN­injected. The activities of serum enzymes, markers of liver function, were increased in the GaIN group compared to normal group and significantly lowered in the DWP-04 pretreated group than in the GaIN group. Hepatic lipid peroxide level and activities of phase 1 enzymes were significantly higher than those of GaIN group compared to normal group and lower in the DWP-04 pretreated group than in the GaIN group, and phase II enzyme activities in liver were lower in the GaIN group than in the normal group and were increased in the DWP-04 pretreated group than in the GaIN group. Total hepatic glutathione content and glutathione biosynthesis enzymes were lower in the GaIN group than in the normal group and were increased in the DWP-04 pretreated group than in the GaIN group. Therefore, the current results indicated that DWP-04 administration alleviated the GaIN-induced adverse effect through enhancing the antioxidant enzyme activities.

Biochemical Characterization of the Dual Positional Specific Maize Lipoxygenase and the Dependence of Lagging and Initial Burst Phenomenon on pH, Substrate, and Detergent during Pre-steady State Kinetics

  • Cho, Kyoung-Won;Jang, Sung-Kuk;Huon, Thavrak;Park, Sang-Wook;Han, Ok-Soo
    • BMB Reports
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    • v.40 no.1
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    • pp.100-106
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    • 2007
  • The wound-inducible lipoxygenase obtained from maize is one of the nontraditional lipoxygenases that possess dual positional specificity. In this paper, we provide our results on the determination and comparison of the kinetic constants of the maize lipoxygenase, with or without detergents in the steady state, and characterization of the dependence of the kinetic lag phase or initial burst, on pH, substrate, and detergent in the pre-steady state of the lipoxygenase reaction. The oxidation of linoleic acid showed a typical lag phase in the pre-steady state of the lipoxygenase reaction at pH 7.5 in the presence of 0.25% Tween-20 detergent. The reciprocal correlation between the induction period and the enzyme level indicated that this lag phenomenon was attributable to the slow oxidative activation of Fe (II) to Fe (III) at the active site of the enzyme as observed in other lipoxygenase reactions. Contrary to the lagging phenomenon observed at pH 7.5 in the presence of Tween-20, a unique initial burst was observed at pH 6.2 in the absence of detergents. To our knowledge, the initial burst in the oxidation of linoleic acid at pH 6.2 is the first observation in the lipoxygenase reaction. Kinetic constants (Km and kcat values) were largely dependent on the presence of detergent. An inverse correlation of the initial burst period with enzyme levels and interpretations on kinetic constants suggested that the observed initial burst in the oxidation of linoleic acid could be due to the availability of free fatty acids as substrates for binding with the lipoxygenase enzyme.

Induction of Nrf2/ARE-mediated cytoprotective genes by red ginseng oil through ASK1-MKK4/7-JNK and p38 MAPK signaling pathways in HepG2 cells

  • Bak, Min Ji;Truong, Van-Long;Ko, Se-Yeon;Nguyen, Xuan Ngan Giang;Jun, Mira;Hong, Soon-Gi;Lee, Jong-Won;Jeong, Woo-Sik
    • Journal of Ginseng Research
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    • v.40 no.4
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    • pp.423-430
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    • 2016
  • Background: The induction of cellular defensive genes such as phase II detoxifying and antioxidant enzymes is a highly effective strategy for protection against carcinogenesis as well as slowing cancer development. Transcription factor Nrf2 (nuclear factor E2-related factor 2) is responsible for activation of phase II enzymes induced by natural chemopreventive compounds. Methods: Red ginseng oil (RGO) was extracted using a supercritical $CO_2$ extraction system and chemical profile of RGO was investigated by GC/MS. Effects of RGO on regulation of the Nrf2/antioxidant response element (ARE) pathway were determined by ARE-luciferase assay, western blotting, and confocal microscopy. Results: The predominant components of RGO were 9,12-octadecadienoic acid (31.48%), bicyclo[10.1.0] tridec-1-ene (22.54%), and 22,23-dihydrostigmasterol (16.90%). RGO treatment significantly increased nuclear translocation of Nrf2 as well as ARE reporter gene activity, leading to upregulation of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase 1. Phosphorylation of the upstream kinases such as apoptosis signal-regulating kinase (ASK)1, mitogen-activated protein kinase (MAPK) kinase (MKK)4/7, c-Jun N-terminal kinase (JNK), and p38 MAPK were enhanced by treatment with RGO. In addition, RGO-mediated Nrf2 expression and nuclear translocation was attenuated by JNK inhibitor SP600125 and p38 MAPK inhibitor SB202190. Conclusion: RGO could be used as a potential chemopreventive agent, possibly by induction of Nrf2/ARE-mediated phase II enzymes via ASK1-MKK4/7-JNK and p38 MAPK signaling pathways.

Induction of the Anticarcinogenic Marker Enzyme, Quinone Reductase, by Dalbergiae Lignum

  • Yin, Hu-Quan;Lee, Bang-Wool;Kim, Youn-Chul;Sohn, Dong-Hwan;Lee, Byung-Hoon
    • Archives of Pharmacal Research
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    • v.27 no.9
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    • pp.919-922
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    • 2004
  • The effect of an extract of Dalbergiae Lignum and four components that were isolated from the extract on the anticarcinogenic phase II marker enzyme, quinone reductase (QR), was investi-gated. Of the solvent extracts of Dalbergiae Lignum, the CH$_2$CI$_2$ fraction was the most potent in inducing QR activity, with a CD value (the concentration required to double the QR activity) of 29.5 $\mu$/mL. The CH$_2$CI$_2$ extract was further separated into six compounds, four of which were identified as 4-methoxydalbergione, latifolin, 4',6-dihydroxy-7-methoxyflavanone, and obtusafu-ran. Obtusafuran [CD = 1.1 $\mu$M; chemopreventive index (CI) = 101.9] and latifolin (CD = 1.7 $\mu$M; CI = 154.6) displayed potent QR inducing activity and high chemopreventive indices. Lati-folin and 4-methoxydalbergione were identified as strong DPPH-scavengers with half-maximal free radical scavenging concentrations of 15.9 and 17.2 $\mu$M, respectively.

Increase in Hepatic DT-Diaphorase Activity by Chronic Administration of Panax ginseng Extract to Mice (생쥐에서의 인삼추출액의 장기간 투여에 의한 간장 DT-Diaphorase 활성의 증가)

  • Lee, Kang-Mee;Wie, Myung-Bok;Song, Dong-Keun;Kim, Yong-Sik;Kim, Yung-Hi
    • Journal of Ginseng Research
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    • v.17 no.2
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    • pp.123-126
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    • 1993
  • Effects of chronic administration of ginseng extracts (30 or 150 mg/kg/day for 52 days, p.o.) to mice on the activities of DT-diaphorase and glutathione S-transferase (GST) in the liver and the brain were studied. The DT-diaphorase activity in the liver was increased over 2-fold at the dose of both 30 and 150 mg/kg/day, while there was no change in the activity of the enzyme in the brain. The GST activity in the liver was increased in a dose-dependent fashion up to 142% of the control value at the dose of 150 mg/kg/day. while there was no change in the activity of the enzyme in the brain. The ginseng-induced increase in the activities of these hepatic phase II drug-metabolizing enzymes which are involved in the detoxification of carcinogens, is suggested to underlie, at least in part, the anticarcinogenic activity of Panax ginseng.

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GSTT1 Null Genotype Distribution in the Kumaun Region of Northern India

  • Bag, Arundhati;Upadhyay, Saloni;Jeena, Lalit M.;Pundir, Princi;Jyala, Narayan S.
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.87-89
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    • 2013
  • Glutathione S-transferases (GSTs) constitute a multigene family of multifunctional phase II metabolic enzymes. GSTT1, an important member of this group has a wide range of substrates including carcinogens. Total homozygous deletion or null genotype resulting in total lack of enzyme activity exists in populations for this enzyme. Since the null genotype may contribute to lower detoxification of carcinogens, this genotype is expected to increase cancer risk. The frequency of the GSTT1 null genotype is known to vary significantly among populations. However, little is known about its distribution in the hilly Kumaun region of northern India. Therefore, in this study, we determined the prevalence of the GSTT1 null polymorphism in the Kumaun popilation by conducting duplex PCR in 365 voluntary healthy individuals. The GSTT1 null genotype was detected in 18.4% of the individuals. Since GSTs play significant role in xenobiotic metabolism, the present data on GSTT1 genotype distribution should contribute in understanding genetic association with cancer risk in this understudied population.