Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) mediates apoptosis induction in fibroblasts with constitutive src or induced ras oncogene expression, whereas nontransformed parental cells and revertants are not affected. This direct link between the transformed phenotype and sensitivity to NO-mediated apoptosis induction seems to be based on the recently described extracellular superoxide anion generation by transformed cells, as NO-mediated apoptosis induction in transformed cells is inhibited by extracellular superoxide dismutase (SOD), by SOD mimetics and by apocynin, an inhibitor of NADPH oxidase. Furthermore, nonresponsive nontransformed cells can be rendered sensitive for NO-mediated apoptosis induction when they are supplemented with xanthine oxidase/xanthine as an extracellular source for superoxide anions. As superoxide anions and NO readily interact in a diffusion-controlled reaction to generate peroxynitrite, peroxynitrite seems to be the responsible apoptosis inducer in NO-mediated apoptosis induction. In line with this conclusion, NO-mediated apoptosis induction in superoxide anion-generating transformed cells is inhibited by the peroxynitrite scavengers ebselen and FeTPPS. Moreover, direct application of peroxynitrite induces apoptosis both in transformed and nontransformed cells, indicating that peroxynitrite is no selective apoptosis inducer per se, but that selective apoptosis induction in transformed cells by NO is achieved through selective peroxynitrite generation. The interaction of NO with target cell derived superoxide anions represents a novel concept for selective apoptosis induction in transformed cells. This mechanism may be the basis for selective apoptosis induction by natural antitumor systems (like macrophages, natural killer cells, granulocytes) that utilize NO for antitumor action. Apoptosis induction mediated by NO involves mitochondrial depolarization and is blocked by Bcl-2 overexpression.
Carcinogenesis 2002 Jun
PMID:Nitric oxide mediates apoptosis induction selectively in transformed fibroblasts compared to nontransformed fibroblasts. 1208 14

Vitis vinifera (grapes) is used as a fruit worldwide and known for its pharmacological properties. The present paper assesses the chemopreventive potential of Vitis vinifera against 12-O-tetradecanoyl-13-phorbol acetate (TPA)-mediated tumor promotion in 7,12-dimethyl-benz[a]anthracene (DMBA) initiated mice skin. Skin tumor initiation was achieved by a single topical application of DMBA (40 microg/animal/0.20 ml acetone) to mice. Two weeks after the initiation, promoting agent, TPA (5.0 microg/animal/0.2 ml acetone) was applied two times a week for 20 weeks. Pretreatment of Vitis vinifera 1h prior to each application of TPA resulted in protection against cutaneous tumorigenesis in dose-dependent manner. This inhibition was evident when tumor data was considered as the percentage of mice with tumor and the number of tumors per mouse. We have shown that typical application of Vitis vinifera prior to that of TPA resulted in significant inhibition against TPA-caused induction of epidermal ODC activity (P<0.001) and DNA synthesis. Application of Vitis vinifera at a dose level of 5.0 mg and 10.0 mg kg(-1) body weight in acetone prior to that of TPA treatment resulted in partial significant inhibition of oxidative stress in dose-dependent manner. The concomitant increase in the microsomal lipid peroxidation and xanthine oxidase activities were significantly reduced (P<0.001). In addition, the depleted level of glutathione and inhibited activities of antioxidant enzymes were recovered to the partial significant level. Hence, it can be suggested that Vitis vinifera can be used as a chemopreventive agent against oxidative stress and carcinogenesis.
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PMID:Chemopreventive effect of Vitis vinifera extract on 12-O-tetradecanoyl-13-phorbol acetate-induced cutaneous oxidative stress and tumor promotion in murine skin. 1245 31

The chemopreventive potential of cycloartenol on benzoyl peroxide and UVB radiation-induced cutaneous tumor promotion markers and oxidative stress in murine skin is assessed. Benzoyl peroxide treatment (20 mg/animal/0.2 ml acetone) and UVB radiation (0.420 J/m(2)/s) caused a decrease in the activities of cutaneous antioxidant enzymes namely, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, phase II metabolizing enzyme such as glutathione-S-transferase and quinone reductase and depletion in the level of cutaneous glutathione. There was also enhancement in cutaneous microsomal lipid peroxidation, xanthine oxidase activity, [(14)C]-ornithine decarboxylase activity and [(3)H]-thymidine incorporation into cutaneous DNA. Cycloartenol was topically applied prior to the application of benzoyl peroxide at dose levels of 0.2 mg and 0.4 mg/kg body weight in acetone, which resulted in significant inhibition of epidermal ornithine decarboxylase activity and DNA synthesis (P < 0.001). There was also significant reduction of lipid peroxidation and xanthine oxidase activity (P < 0.001). In addition, the depleted levels of glutathione, inhibited activities of antioxidant and phase II metabolizing enzymes, were also recovered to a significant level (P < 0.001). The data indicate that cycloartenol is an effective chemopreventive agent in skin carcinogenesis.
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PMID:Inhibition of benzoyl peroxide and ultraviolet-B radiation induced oxidative stress and tumor promotion markers by cycloartenol in murine skin. 1280 13

Aristolochic acid (AA), a naturally occurring nephrotoxin and carcinogen, has been associated with the development of urothelial cancer in humans. Understanding which human enzymes are involved in AA metabolism is important in the assessment of an individual's susceptibility to this carcinogen. Using the 32P-postlabeling assay we examined the ability of enzymes of cytosolic samples from 10 different human livers and from one human kidney to activate the major component of the plant extract AA, 8-methoxy- 6-nitro-phenanthro-(3,4-d)-1,3-dioxolo-5-carboxylic acid (AAI), to metabolites forming adducts in DNA. Cytosolic fractions of both organs generated AAI-DNA adduct patterns reproducing those found in renal tissues from humans exposed to AA. 7-(Deoxyadenosin-N6-yl)aristolactam I, 7-(deoxyguanosin-N2-yl)aristolactam I and 7-(deoxyadenosin-N6-yl)aristolactam II, indicating a possible demethoxylation reaction of AAI, were identified as AA-DNA adducts formed from AAI by all human hepatic and renal cytosols. To define the role of human cytosolic reductases in the activation of AAI, we investigated the modulation of AAI-DNA adduct formation by cofactors or selective inhibitors of the NAD(P)H:quinone oxidoreductase (NQO1), xanthine oxidase (XO) and aldehyde oxidase. We also determined whether the activities of NQO1 and XO in different human hepatic cytosolic samples correlated with the levels of AAI-DNA adducts formed by the same cytosolic samples. Based on these studies, we attribute most of the activation of AA in human cytosols to NQO1, although a role of cytosolic XO cannot be ruled out. With purified NQO1 from rat liver and kidney and XO from buttermilk, the major role of NQO1 in the formation of AAI-DNA adducts was confirmed. The orientation of AAI in the active site of human NQO1 was predicted from molecular modeling based on published X-ray structures. The results demonstrate for the first time the potential of human NQO1 to activate AAI by nitroreduction.
Carcinogenesis 2003 Oct
PMID:Human cytosolic enzymes involved in the metabolic activation of carcinogenic aristolochic acid: evidence for reductive activation by human NAD(P)H:quinone oxidoreductase. 1286 22

2-Nitroanisole (2-NA) is an important industrial pollutant and a potent bladder carcinogen for rodents. The mechanism of its carcinogenicity was investigated in this study. Here we have used two independent methods, (32)P-post-labeling and (3)H-labeled 2-NA, to show that 2-NA binds covalently to DNA in vitro after reductive activation by human hepatic cytosol and xanthine oxidase (XO). We also investigated the capacity of 2-NA to form DNA adducts in vivo. Male Wistar rats were treated i.p. with 2-NA (0.15 mg/kg body wt daily for 5 days) and DNA from several organs was analyzed by (32)P-post-labeling. Two 2-NA-specific DNA adducts, identical to those found in DNA incubated with 2-NA and human hepatic cytosol or XO in vitro, were detected in the urinary bladder (3.4 adducts/10(7) nt), the target organ, and, to a lesser extent, in liver, kidney and spleen. The two DNA adducts found in rat tissues in vivo were identified as deoxyguanosine adducts derived from a 2-NA reductive metabolite, N-(2-methoxyphenyl)hydroxylamine. This reactive metabolite of 2-NA was identified in incubations with human hepatic cytosol, besides 2-methoxyaniline (o-anisidine). The results of our study, the first report on the potential of human cytosolic enzymes to contribute to the activation of 2-NA by nitroreduction, strongly suggest a carcinogenic potency of this rodent carcinogen for humans.
Carcinogenesis 2004 May
PMID:Identification of a genotoxic mechanism for 2-nitroanisole carcinogenicity and of its carcinogenic potential for humans. 1472 94

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 an earlier communication we reported that Nigella sativa suppresses potassium bromate-induced renal oxidative damage. In the present study, we report the chemopreventive effect of Nigella sativa against ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, hyperproliferative response and renal carcinogenesis. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content, antioxidant enzymes and phase II metabolizing enzymes. It also caused increase in blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [H] incorporation into renal DNA. It also enhanced DEN (N-diethylnitrosamine)-initiated renal carcinogenesis by increasing the percentage incidence of tumours. Treatment of rats orally with Nigella sativa (50 and 100 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 tumours. Renal glutathione content (P<0.01), glutathione-metabolizing enzymes (P<0.001) and antioxidant enzymes were also recovered to significant levels (P<0.001). Thus, our data suggest that Nigella sativa 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:Inhibition of two stage renal carcinogenesis, oxidative damage and hyperproliferative response by Nigella sativa. 1578 20

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

The aim of the present study was to determine the potential beneficial effects of Ficus racemosa extract. Potassium bromate (KBrO3), a potent nephrotoxic agent that induces renal carcinogenesis and acts as tumour promoter in carcinogen-initiated animals was used as a model to induce renal injury. In this study, we show the chemopreventive effect of Ficus racemosa extract (Moraceae) on KBrO3-mediated renal oxidative stress and cell promotion response in rats. KBrO3 (125 mg/kg body weight, intraperitoneally) enhanced lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content and antioxidant enzymes. KBrO3 treatment also induced tumour promotion markers, viz., ornithine decarboxylase 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 Ficus racemosa extract (200 mg/kg body weight and 400 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P<0.05), lipid peroxidation (P<0.001), gamma-glutamyl transpeptidase (P<0.001) and H(2O2 (P<0.001). There was significant recovery of renal glutathione content (P<0.01) and antioxidant enzymes (P<0.001). There was also reversal in the enhancement of renal ornithine decarboxylase activity, DNA synthesis, blood urea nitrogen and serum creatinine (P<0.001). Our results suggest that Ficus racemosa extract is a potent chemopreventive agent and suppresses KBrO3-mediated nephrotoxicity in rats.
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PMID:Modulatory effect of Ficus racemosa: diminution of potassium bromate-induced renal oxidative injury and cell proliferation response. 1623 39


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