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Quinone Reductase (quinone + reductase)
Selected AbstractsCharacterization of tanshinones with quinone reductase induction activity from Radix Salvia miltiorrhiza by liquid chromatography/tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2009Zhongjun Ma Quinone reductase (QR) induction is a reliable biomarker of phase II enzyme induction. In this study, glutathione (GSH) was employed and a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was introduced to reveal the chemical constituents with QR activity from the ethyl acetate extract of roots Salvia miltiorrhiza (,Danshen') and nine tanshinones (9, 13, 17-19, 21, 24,26), which could conjugate with GSH, were characterized by LC/MS/MS and considered to have QR activities. Then, thirteen tanshinones, including six compounds (17, 18, 21, 24,26) of the above nine tanshinones, were isolated to conduct QR induction evaluation, and it was found that miltirone and its derivatives (18, 20, 24, 26) exhibited significant activities. The GSH conjugate abilities of the isolated tanshinones were also examined; this showed that compounds 18, 20, 24 and 26 had good conjugating abilities with GSH. Compared with the in vitro bioactivity screening results, this proved that conjugate ability is related with QR activity, so an LC/MS/MS method can be applied to find more active compounds. Copyright © 2009 John Wiley & Sons, Ltd. [source] Effects of benzo[a]pyrene on tissue activities of metabolizing enzymes and antioxidant system in normal and protein-malnourished ratsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2003Osama A. Badary Abstract The effects of benzo[a]pyrene (B[a]P) on some drug-metabolizing and antioxidant systems in liver, lung, and stomach were investigated in normal and protein malnutrition (PM) rats. PM significantly inhibited tissue glutathione (GSH) content and increased hepatic lipid peroxidation. Cytochrome P450 isoform CYP1A1 was significantly increased in various tissues (42,73%). Also, lung glutathione S-transferase (GST) activity was significantly decreased (19%) in PM rats. On the other hand, B[a]P significantly induced tissue GSH of control and PM rats. Also, hepatic lipid peroxidation were significantly increased in control rats treated with B[a]P. Superoxide dismutase (SOD) activity was decreased by B[a]P treatment in PM rat stomach. B[a]P significantly induced both quinone reductase (QR) (in all tissues) and hepatic GST of control and PM rats. GST activity in PM rat liver was significantly higher than that of control rat liver after B[a]P treatment. Also, B[a]P induced hepatic CYP1A1 by 32-fold and 27-fold (P , 0.05) in control and PM rats, respectively. Stomach and hepatic UDP-glucuronosyltransferase activities were significantly decreased (34%) and increased (74%), respectively by B[a]P in PM rats. The results suggest that PM status has a modifying effect on the response of some antioxidant and metabolizing systems to a well-known carcinogen risk. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:86,91, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10064 [source] Inhibitory effect of apigenin on benzo(a)pyrene-mediated genotoxicity in Swiss albino miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2006Tajdar Husain Khan Apigenin, a bioflavonoid, is abundantly present in fruits and vegetables and possesses potential chemopreventive properties against a wide variety of chronic diseases. In this study we investigated the anti-genotoxic effects of apigenin against a known genotoxicant, benzo(a)pyrene (B(a)P) (125 mg kg,1 orally) toxicity in Swiss albino mice. B(a)P administration led to induction of cytochrome P-450 (CYP), aryl hydrocarbon hydroxylase (AHH) and DNA strand breaks (P < 0.001), which was suppressed by apigenin (2.5 and 5 mg kg,1 orally) dose dependently (P < 0.001). B(a)P-induced depletion in the level of reduced glutathione (GSH), quinone reductase (QR) and glutathione-S-transferase (GST) was also shown to be restored by apigenin pre-treatment (P < 0.001). A simultaneous significant and dose-dependent reduction was noted in DNA strand breaks and in-vivo DNA damage (P < 0.001), which gives some insight into restoration of DNA integrity in modulator groups. These results strongly support the protective nature of apigenin against B(a)P-induced toxicity. [source] Direct analysis of single leaf disks for chemopreventive glucosinolatesPHYTOCHEMICAL ANALYSIS, Issue 3 2002Qiaomei Wang Abstract Natural isothiocyanates, produced during plant tissue damage from methionine-derived glucosinolates, are potent inducers of mammalian phase 2 detoxification enzymes such as quinone reductase (QR). A greatly simplified bioassay for glucosinolates based on induction and colorimetric detection of QR activity in murine hepatoma cells is described. It is demonstrated that excised leaf disks of Arabidopsis thaliana (ecotype Columbia) can directly and reproducibly substitute for cell-free leaf extracts as inducers of murine QR, which reduces sample preparation to a minimum and maximizes throughput. A comparison of 1 and 3,mm diameter leaf disks indicated that QR inducer potency was proportional to disk circumference (extent of tissue damage) rather than to area. When compared to the QR inducer potency of the corresponding amount of extract, 1,mm leaf disks were equally effective, whereas 3,mm disks were 70% as potent. The QR inducer potency of leaf disks correlated positively with the content of methionine-derived glucosinolates, as shown by the analysis of wild-type plants and mutant lines with lower or higher glucosinolate content. Thus, the microtitre plate-based assay of single leaf disks provides a robust and inexpensive visual method for rapidly screening large numbers of plants in mapping populations or mutant collections and may be applicable to other glucosinolate-producing species. Copyright © 2002 John Wiley & Sons, Ltd. [source] Thymoquinone supplementation induces quinone reductase and glutathione transferase in mice liver: possible role in protection against chemical carcinogenesis and toxicityPHYTOTHERAPY RESEARCH, Issue 9 2009Mahmoud N. Nagi Abstract Thymoquinone (TQ), the main constituents of the volatile oil from Nigella sativa seeds is reported to protect laboratory animals against chemical carcinogenesis and toxicity through mechanism(s) that is not fully understood. Among possible mechanism(s), protection could be mediated via induction of detoxifying enzymes, including quinone reductase and glutathione transferase. This study was undertaken to investigate whether oral administration of TQ increases the activities of quinone reductase and glutathione transferase in mice liver. Overdose of TQ, when administered intraperitoneally, caused a marked depletion of hepatic glutathione in both a time- and dose- dependent manner, a characteristic of a group of compounds known as Michael reaction acceptors which are known to act as inducers of enzymes that protect against chemical carcinogenesis and toxicity. TQ was given (1, 2 and 4 mg/kg/day p.o.) for five days to test the chemical inducibility of quinone reductase and glutathione transferase in mice liver. TQ administration produced significant increase in the activities of quinone reductase (147, 196 and 197% of control, respectively) and glutathione transferase (125, 152 and 154% of control, respectively). In conclusion, oral administration of TQ is effective in increasing the activities of quinone reductase and glutathione transferase and makes TQ a promising prophylactic agent against chemical carcinogenesis and toxicity. Copyright © 2009 John Wiley & Sons, Ltd. [source] Nrf2-mediated induction of detoxifying enzymes by alantolactone present in Inula heleniumPHYTOTHERAPY RESEARCH, Issue 11 2008Ji Yeon Seo Abstract Our previous study showed that a methanol extract of Inula helenium had the potential to induce detoxifying enzymes such as quinone reductase (QR) and glutathione S -transferase (GST) activity. In this study the methanol extract was further fractionated using silica gel chromatography and vacuum liquid chromatography, to yield pure compounds alantolactone and isoalantolactone as QR inducers. Alantolactone caused a dose-dependent induction of antioxidant enzymes including QR, GST, , -glutamylcysteine synthase, glutathione reductase, and heme oxygenase 1 in hepa1c1c7 mouse hepatoma cells. The compound increased the luciferase activity of HepG2-C8 cells, transfectants carrying antioxidant response element (ARE)-luciferase gene, in a dose-dependent manner, suggesting ARE-mediated transcriptional activation of antioxidant enzymes. Alantolactone also stimulated the nuclear accumulation of Nrf2 that was inhibited by phosphatidylinositol 3-kinase (PI3K) inhibitors. In conclusion, alantolactone appears to induce detoxifying enzymes via activation of PI3K and JNK signaling pathways, leading to translocation of Nrf2, and subsequent interaction between Nrf2 and ARE in the encoding genes. Copyright © 2008 John Wiley & Sons, Ltd. [source] Tephrosia purpurea Ameliorates N-Diethylnitrosamine and Potassium Bromate-Mediated Renal Oxidative Stress and Toxicity in Wistar RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2001Naghma Khan 1999). The present study was designed to investigate a chemopreventive efficacy of T. purpurea against N-diethylnitrosamine-initiated and potassium bromate-mediated oxidative stress and toxicity in rat kidney. A single intraperitoneal dose of N-diethylnitrosamine (200 mg/kg body weight) one hr prior to the dose of KBrO3 (125 mg/kg body weight) increases microsomal lipid peroxidation and the activity of xanthine oxidase and decreases the activities of renal antioxidant enzymes viz., catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase, phase II metabolizing enzymes such as glutathione-S-transferase and quinone reductase and causes depletion in the level of renal glutathione content. A sharp increase in blood urea nitrogen and serum creatinine has also been observed. Prophylactic treatment of rats with T. purpurea at doses of 5 mg/kg body weight and 10 mg/kg body weight prevented N-diethylnitrosamine-initiated and KBrO3 promoted renal oxidative stress and toxicity. The susceptibility of renal microsomal membrane for iron ascorbate-induced lipid peroxidation and xanthine oxidase activities were significantly reduced (P<0.01). The depleted levels of glutathione, the inhibited activities of antioxidant enzymes, phase II metabolizing enzymes and the enhanced levels of serum creatinine and blood urea nitrogen were recovered to a significant level (P<0.01). All the antioxidant enzymes were recovered dose-dependently. Our data indicate that T. purpurea besides a skin antioxidant can be a potent chemopreventive agent against renal oxidative stress and carcinogenesis induced by N-diethylnitrosamine and KBrO3. [source] Myrica nagi Attenuates Cumene Hydroperoxide-Induced Cutaneous Oxidative Stress and Toxicity in Swiss Albino MiceBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2000Aftab Alam In recent years, considerable efforts have been made to identify new chemopreventive agents which could be useful for man. Myrica nagi, a subtropical shrub, has been shown to possess significant activity against hepatotoxicity and other pharmacological and physiological disorders. We have shown a chemopreventive effect of Myrica nagi on cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in mice. Cumene hydroperoxide treatment at a dose level of 30 mg/animal/0.2 ml acetone enhances susceptibility of cutaneous microsomal membrane for iron-ascorbate-induced lipid peroxidation and induction of xanthine oxidase activity which are accompanied by decrease in the activities of cutaneous antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and depletion in the level of cutaneous glutathione. Parallel to these changes a sharp decrease in the activities of phase II metabolizing enzymes such as glutathione S-transferase and quinone reductase has been observed. Application of Myrica nagi at doses of 2.0 mg and 4.0 mg/kg body weight in acetone prior to that of cumene hydroperoxide (30 mg/animal/0.2 ml acetone) treatment resulted in significant inhibition of cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in a dose-dependent manner. Enhanced susceptibility of cutaneous microsomal membrane for lipid peroxidation induced by iron ascorbate and xanthine oxidase activities were significantly reduced (P<0.05). In addition the depleted level of glutathione, the inhibited activities of antioxidants, and phase II metabolizing enzymes were recovered to a significant level (P<0.05). The protective effect of Myrica nagi was dose-dependent. In summary our data suggest that Myrica nagi is an effective chemopreventive agent in skin and capable of ameliorating cumene hydroperoxide-induced cutaneous oxidative stress and toxicity. [source] Production, characterization and determination of the real catalytic properties of the putative ,succinate dehydrogenase' from Wolinella succinogenesMOLECULAR MICROBIOLOGY, Issue 5 2009Hanno D. Juhnke Summary Both the genomes of the epsilonproteobacteria Wolinella succinogenes and Campylobacter jejuni contain operons (sdhABE) that encode for so far uncharacterized enzyme complexes annotated as ,non-classical' succinate:quinone reductases (SQRs). However, the role of such an enzyme ostensibly involved in aerobic respiration in an anaerobic organism such as W. succinogenes has hitherto been unknown. We have established the first genetic system for the manipulation and production of a member of the non-classical succinate:quinone oxidoreductase family. Biochemical characterization of the W. succinogenes enzyme reveals that the putative SQR is in fact a novel methylmenaquinol:fumarate reductase (MFR) with no detectable succinate oxidation activity, clearly indicative of its involvement in anaerobic metabolism. We demonstrate that the hydrophilic subunits of the MFR complex are, in contrast to all other previously characterized members of the superfamily, exported into the periplasm via the twin-arginine translocation (tat)-pathway. Furthermore we show that a single amino acid exchange (Ala86,His) in the flavoprotein of that enzyme complex is the only additional requirement for the covalent binding of the otherwise non-covalently bound FAD. Our results provide an explanation for the previously published puzzling observation that the C. jejuni sdhABE operon is upregulated in an oxygen-limited environment as compared with microaerophilic laboratory conditions. [source] | |||||||||||||