Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemoprevention of free radical-mediated diseases including cancer by natural products is an emerging discipline due to its wider applicability and acceptance. The present study deals with the chemopreventive effect of Salix caprea against phorbol ester-induced oxidative stress and tumor promotion in murine skin. In the present investigation, it was observed that a single application of 12-O-tetradecanoyl-13-phorbol acetate (TPA) (20 nmol/0.2 ml acetone/animal) caused a significant (P < 0.05) depletion of cutaneous antioxidants viz., glutathione, glutathione reductase, glutathione peroxidase, catalase and phase II drug metabolizing enzymes viz., glutathione-S-transferase, quinone reductase. An increase in the hydrogen peroxide generation and protein oxidation (measured in terms of protein carbonyl content) was also observed with a single application of TPA. However, the pretreatment of animals with different doses of Salix caprea (0.5, 1.0 and 1.5 mg/kg/0.2 ml acetone) caused a significant recovery in the TPA-mediated depletion in antioxidant levels. The pretreatment of animals with Salix caprea was observed to inhibit the TPA-mediated depletion in phase II enzymes. It was also observed that Salix caprea reversed the TPA-mediated depletion in the activity of phase II enzymes that is an important characteristic of cancer chemopreventive agents. Phorbol esters are known to induce the tumor promotion by increasing rate of DNA synthesis, ornithine decarboxylase activity (ODC), and xanthine oxidase activity. In the present investigation, it was observed that the pretreatment of animals with Salix caprea caused a significant (P < 0.05) depletion in the TPA-induced DNA synthesis, ODC and xanthine oxidase activity in mice skin. Salix caprea significantly reduced the tumor promotion in mice skin when tested in two-stage chemical carcinogenesis model. It was observed to inhibit significantly P < 0.05) the 7,12-dimethyl benz[a] anthracene (DMBA)-initiated phorbol ester promoted skin carcinogenesis. It was concluded from the results that Salix caprea is an effective antioxidant and chemopreventive agent against phorbol ester-induced tumor promotion.
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PMID:Salix caprea inhibits skin carcinogenesis in murine skin: inhibition of oxidative stress, ornithine decarboxylase activity and DNA synthesis. 1512 Apr 50

In our earlier communication we have shown that Lupeol inhibits early responses of tumour induction in murine skin. The free radical mediated damage to the cellular macromolecules such as DNA, proteins, lipids and alteration in the activities of quinone reductase and xanthine oxidase are important biochemical parameters of tumor development. The suppression of free radical mediated damage to cellular macromolecules and induction of quinone reductase along with depletion of xanthine oxidase are prominent characteristics of chemopreventive agents. In the present investigation, we have elucidated the mechanism of action of lupeol (Lup-20 (29)-en-3beta-ol), a triterpene found in moderate amount in many vegetables, fruits and anti-tumor herbs. In the present investigation, lupeol significantly reduced the free radical mediated DNA-sugar damage and microsomal lipid peroxidation in an iron/ascorbate free radical generating system in vitro. Benzoyl peroxide, a known free radical generating tumor promoter mediated oxidation of proteins and modulation in the activities of quinone reductase as well as xanthine oxidase was significantly prevented by lupeol when tested on murine skin in vivo. It was concluded from this study that lupeol acts as an effective chemopreventive agent against cutaneous toxicity.
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PMID:Lupeol, a triterpene, prevents free radical mediated macromolecular damage and alleviates benzoyl peroxide induced biochemical alterations in murine skin. 1524 79

Ferric nitrilotriacetate (Fe-NTA) is a known potent nephrotoxic agent. In this communication, we report the chemopreventive effect of soy isoflavones on renal oxidative stress, toxicity and cell proliferation response in Wistar rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances gamma-glutamyl transpeptidase, renal lipid peroxidation, xanthine oxidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase. Fe-NTA treatment also induced tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. A sharp elevation in the levels of blood urea nitrogen and serum creatinine has also been observed. Treatment of rats orally with soy isoflavones (5 mg/kg body weight and 10 mg/kg body weight) resulted in significant decreases in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Renal glutathione content (P < 0.01), glutathione metabolizing enzymes (P < 0.001) and antioxidant enzymes were also returned to normal levels (P < 0.001). Thus, our data suggest that soy isoflavones may be used as an effective chemopreventive agent against Fe-NTA-mediated renal oxidative stress, toxicity and cell proliferation response in Wistar rats.
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PMID:Induction of renal oxidative stress and cell proliferation response by ferric nitrilotriacetate (Fe-NTA): diminution by soy isoflavones. 1529 41

Potassium bromate (KBrO3) is a potent nephrotoxic agent. In this study, we show the modulatory effect of soy isoflavones on KBrO3-mediated renal oxidative stress and subsequent cell proliferation response in Wistar rats. KBrO3 (125 mg/kg body weight, intraperitoneally) caused reduction in renal glutathione content, activities of renal anti-oxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase with enhancement in xanthine oxidase, lipid peroxidation, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2). KBrO3 treatment also induced blood urea nitrogen, serum creatinine and tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. Treatment of rats orally with soy isoflavones (5 mg/kg body weight and 10 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P < 0.05), lipid peroxidation, gamma-glutamyl transpeptidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). There was also significant recovery of renal glutathione content (P < 0.01), anti-oxidant enzymes and phase-II metabolising enzymes (P < 0.001). Thus, our results show that soy isoflavones acts as potent chemopreventive agent against KBrO3-mediated renal oxidative stress, toxicity and subsequent cell proliferation response in Wistar rats.
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PMID:Abrogation of potassium bromate-induced renal oxidative stress and subsequent cell proliferation response by soy isoflavones in Wistar rats. 1529 31

A total of 6 newly-synthesized styrylchromones (SC-1 approximately SC-6) were compared for their cytotoxic activity against three normal oral human cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF) and four human tumor cell lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG, promyelocytic leukemia HL-60). All compounds showed higher cytotoxic activity against tumor cell lines than against normal cells. Among the 6 compounds, SC-3, SC-4 and SC-5, which have one to three methoxy groups, showed higher tumor specificity and water solubility. The cytotoxic activity of SC-3 and SC-5 was slightly reduced by a lower concentration of NADH, a quinone reductase, but that of SC-3 was enhanced by higher concentrations of NADH, possibly due to demethylation of the methoxy groups. Agarose gel electrophoresis demonstrated that SC-3 and SC-5 induced intemucleosomal DNA fragmentation in HL-60 cells and production of large DNA fragment in HSC-2 cells. Both SC-3 and SC-5 enhanced the enzymatic activity to cleave the substrates for caspases 3, 8 and 9, suggesting the activation of both extrinsic and intrinsic apoptosis pathways. ESR spectroscopy showed that these compounds produced no detectable amount of radical and did not scavenge superoxide anion generated by the hypoxanthine-xanthine oxidase reaction. The highly tumor-specific cytotoxic action and apoptosis-inducing capability of SC-3 and SC-5 suggest their applicability for cancer chemotherapy.
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PMID:Cytotoxic activity of styrylchromones against human tumor cell lines. 1579 68

3-Nitrobenzanthrone (3-nitro-7H-benz[de]anthracen-7-one, 3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust and air pollution. We compared the ability of human hepatic cytosolic samples to catalyze DNA adduct formation by 3-NBA. Using the (32)P-postlabeling method, we found that 12/12 hepatic cytosols activated 3-NBA to form multiple DNA adducts similar to those formed in vivo in rodents. By comparing 3-NBA-DNA adduct formation in the presence of cofactors of NAD(P)H:quinone oxidoreductase (NQO1) and xanthine oxidase, most of the reductive activation of 3-NBA in human hepatic cytosols was attributed to NQO1. Inhibition of adduct formation by dicoumarol, an NQO1 inhibitor, supported this finding and was confirmed with human recombinant NQO1. When cofactors of N,O-acetyltransferases (NAT) and sulfotransferases (SULT) were added to cytosolic samples, 3-NBA-DNA adduct formation increased 10- to 35-fold. Using human recombinant NQO1 and NATs or SULTs, we found that mainly NAT2, followed by SULT1A2, NAT1, and, to a lesser extent, SULT1A1 activate 3-NBA. We also evaluated the role of hepatic NADPH:cytochrome P450 oxidoreductase (POR) in the activation of 3-NBA in vivo by treating hepatic POR-null mice and wild-type littermates i.p. with 0.2 or 2 mg/kg body weight of 3-NBA. No difference in DNA binding was found in any tissue examined (liver, lung, kidney, bladder, and colon) between null and wild-type mice, indicating that 3-NBA is predominantly activated by cytosolic nitroreductases rather than microsomal POR. Collectively, these results show the role of human hepatic NQO1 to reduce 3-NBA to species being further activated by NATs and SULTs.
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PMID:Environmental pollutant and potent mutagen 3-nitrobenzanthrone forms DNA adducts after reduction by NAD(P)H:quinone oxidoreductase and conjugation by acetyltransferases and sulfotransferases in human hepatic cytosols. 1580 61

The present study investigates the prophylactic effect of Nymphaea alba against ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in Wistar rats. Treatment with Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhanced iron-ascorbate-induced renal lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase. It also elevated the levels of blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. It also enhanced DEN-initiated renal carcinogenesis by increasing the percentage incidence of renal tumors. Treatment of rats orally with N. alba (100 and 200 mg/kg body weight) resulted in significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity, DNA synthesis (p < 0.001) and incidence of tumors. Renal glutathione content (p < 0.01), glutathione metabolizing enzymes (p < 0.001) and antioxidant enzymes were also recovered to significant level (p < 0.001). Thus, our results show that N. alba is a potent chemopreventive agent and suppresses Fe-NTA-induced oxidative stress, hyperproliferative response and renal carcinogenesis in Wistar rats.
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PMID:Anticarcinogenic effect of Nymphaea alba against oxidative damage, hyperproliferative response and renal carcinogenesis in Wistar rats. 1588 50

Ferric nitrilotriacetate (Fe-NTA) is a well-known renal carcinogen. In this communication, we show the chemopreventive effect of Ficus racemosa extract against Fe-NTA-induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H(2)O(2)) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [(3)H] incorporation into renal DNA. It also enhances DEN (N-diethylnitrosamine) initiated renal carcinogenesis by increasing the percentage incidence of tumors. Treatment of rats orally with F. racemosa extract (200 and 400 mg/kg body weight) resulted in significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H(2)O(2) generation, blood urea nitrogen, serum creatinine, renal ODC activity, DNA synthesis (P<0.001) and incidence of tumors. Renal glutathione content (P<0.01), glutathione metabolizing enzymes (P<0.001) and antioxidant enzymes were also recovered to significant level (P<0.001). Thus, our data suggests that F. racemosa extract is a potent chemopreventive agent and suppresses Fe-NTA-induced renal carcinogenesis and oxidative damage response in Wistar rats.
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PMID:Chemomodulatory effect of Ficus racemosa extract against chemically induced renal carcinogenesis and oxidative damage response in Wistar rats. 1588 7

Resveratrol (3,4',5-trihydroxystilbene), a polyphenolic compound found in mulberries, grapes and red wine has been demonstrated to be capable of protecting against oxidative cardiovascular pathophysiology. However, the underlying cellular and biochemical mechanisms remain to be elucidated. This study was undertaken to determine if resveratrol could upregulate endogenous antioxidants and phase 2 enzymes in cultured aortic smooth muscle cells (ASMCs), and if such increased cellular defenses could provide protection against oxidative and electrophilic vascular cell injury. Incubation of rat ASMCs with resveratrol at low micromolar concentrations resulted in a significant induction of a scope of cellular antioxidants and phase 2 enzymes in a concentration- and/or time-dependent fashion. These cytoprotective factors include superoxide dismutase, catalase, glutathione, glutathione reductase, glutathione peroxidase, glutathione S-transferase (GST), and NAD(P)H:quinone oxidoreductase-1 (NOQ1). Notably, induction of catalase, GST, and NOQ1 was most remarkable among the above resveratrol-inducible antioxidants and phase 2 enzymes. Moreover, resveratrol treatment also significantly increased the mRNA expression of catalase, GSTA1, and NQO1 in a time-dependent manner. Pretreatment of ASMCs with resveratrol afforded a remarkable protection against xanthine oxidase (XO)/xanthine- or 4-hydroxy-2-nonenal-induced cytotoxicity, as assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Resveratrol pretreatment also led to a marked reduction in intracellular accumulation of reactive oxygen species in ASMCs after incubation with XO/xanthine. Taken together, this study demonstrates that a scope of key endogenous antioxidants and phase 2 enzymes in cultured ASMCs can be upregulated by resveratrol at low micromolar concentrations, and that such chemically-elevated cellular defenses rendered cells increased resistance to oxidative and electrophilic stress. The results of this study thus suggested a new mechanism, which might contribute to the cardiovascular protective effects of resveratrol.
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PMID:Upregulation of endogenous antioxidants and phase 2 enzymes by the red wine polyphenol, resveratrol in cultured aortic smooth muscle cells leads to cytoprotection against oxidative and electrophilic stress. 1616 43

3-Nitrobenzanthrone (3-NBA) is a potent mutagen and potential human carcinogen identified in diesel exhaust and ambient air particulate matter. Previously, we detected the formation of 3-NBA-derived DNA adducts in rodent tissues by 32P-postlabeling, all of which are derived from reductive metabolites of 3-NBA bound to purine bases, but structural identification of these adducts has not yet been reported. We have now prepared 3-NBA-derived DNA adduct standards for 32P-postlabeling by reacting N-acetoxy-3-aminobenzanthrone (N-Aco-ABA) with purine nucleotides. Three deoxyguanosine (dG) adducts have been characterised as N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone-3'-phosphate (dG3'p-C8-N-ABA), 2-(2'-deoxyguanosin-N2-yl)-3-aminobenzanthrone-3'-phosphate (dG3'p-N2-ABA) and 2-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone-3'-phosphate (dG3'p-C8-C2-ABA), and a deoxyadenosine (dA) adduct was characterised as 2-(2'-deoxyadenosin-N6-yl)-3-aminobenzanthrone-3'-phosphate (dA3'p-N6-ABA). 3-NBA-derived DNA adducts formed experimentally in vivo and in vitro were compared with the chemically synthesised adducts. The major 3-NBA-derived DNA adduct formed in rat lung cochromatographed with dG3'p-N2-ABA in two independent systems (thin layer and high-performance liquid chromatography). This is also the major adduct formed in tissue of rats or mice treated with 3-aminobenzanthrone (3-ABA), the major human metabolite of 3-NBA. Similarly, dG3'p-C8-N-ABA and dA3'p-N6-ABA cochromatographed with two other adducts formed in various organs of rats or mice treated either with 3-NBA or 3-ABA, whereas dG3'p-C8-C2-ABA did not cochromatograph with any of the adducts found in vivo. Utilizing different enzymatic systems in vitro, including human hepatic microsomes and cytosols, and purified and recombinant enzymes, we found that a variety of enzymes [NAD(P)H:quinone oxidoreductase, xanthine oxidase, NADPH:cytochrome P450 oxidoreductase, cytochrome P450s 1A1 and 1A2, N,O-acetyltransferases 1 and 2, sulfotransferases 1A1 and 1A2, and myeloperoxidase] are able to catalyse the formation of 2-(2'-deoxyguanosin-N2-yl)-3-aminobenzanthrone, N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone and 2-(2'-deoxyadenosin-N6-yl)-3-aminobenzanthrone in DNA, after incubation with 3-NBA and/or 3-ABA.
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PMID:Identification of three major DNA adducts formed by the carcinogenic air pollutant 3-nitrobenzanthrone in rat lung at the C8 and N2 position of guanine and at the N6 position of adenine. 1633 2


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