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)

Cells from patients with ataxia-telangiectasia (AT) are more sensitive than cells from normal individuals to a number of compounds which induce DNA damage via oxygen-derived free radical attack. We tested the hypothesis that AT cells would show a sensitivity to reactive oxygen species (ROS) generated by activated inflammatory cells. AT cells were exposed to neutrophils activated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or to xanthine/xanthine oxidase (X/XO), an enzyme system which generates superoxide and hydrogen peroxide. Induced micronuclei (MN) frequencies (corrected for spontaneous MN frequencies) were significantly higher in AT cell cultures than in cultures from normal individuals (comparison of MN frequencies of AT vs. normal cultures: for treatment with activated neutrophils, P = 0.003; for X/XO, P = 0.05). The comet assay was used to determine whether the elevated chromosomal damage in the treated AT cells was due to a difference in strand breakage or its rejoining. X/XO treatment was used in studies of single-stranded (SS) DNA breakage, and X-ray treatment for double-stranded (DS) DNA damage. AT and normal cells showed no significant differences in the initial levels of SS (P = 0.29) or DS (P = 0.91) DNA damage. Likewise, they exhibited similar rejoining kinetics (rejoining half-time for SS = 10 min, for DS = 30 min). These data support the involvement of the AT loci in determining a cell's ability to deal with oxidative stress, although the mechanism underlying this effect has yet to be resolved. The data also suggest that AT patients are at elevated risk of sustaining DNA damage in tissues undergoing inflammatory reactions.
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PMID:Response of fibroblast cultures from ataxia-telangiectasia patients to reactive oxygen species generated during inflammatory reactions. 792 23

In order to enhance the lipophilicity and develop the efficacy of ascorbic acid (ASA), we synthesized lecithinized ascorbic acid (PC-AS), in which a lecithin was covalently bound to ASA. Its pharmacological activity was also evaluated. The IC50 value of scavenge superoxide anions generated from hypoxanthine in combination with xanthine oxidase, indicated that the antioxidative activity of PC-AS (IC50; 22.19 microM) was about 60% of that shown by ASA (IC50; 13.35 microM). Also, PC-AS suppressed in vitro cell growth of Meth A-T, a highly metastatic cell line established by us. Although its potency (IC50; 110.0 microM) was a little lower than that of ASA, dramatic suppression was observed under serum-free culture conditions (IC50; 13.0 microM). In addition, N-acetylcysteine (NAC), an antioxidant, showed an additive inhibitory effect on cell growth in combination with PC-AS and ASA. Biodistribution studies revealed that PC-AS persisted longer in the blood (AUC0-240 min; 182.8 nmole min ml-1) than ASA (AUC0-240 min; 79.35 nmole min ml-1). It should be noted that intravenous preadministration of PC-AS significantly and dose-dependently reduced the number of colony formation in an experimental murine pulmonary metastasis model. ASA had little effect. [3H]-labeled Meth A-T cells predominantly accumulated in the lung, metastatic target organ, which was reduced by PC-AS. Our in vivo study showed that PC-AS could not totally prevent pulmonary invasion of Meth A-T cells, however, PC-AS effectively inhibited the number of metastatic colony formation. PC-AS's potency was superior to that of unmodified ASA. These findings might be in part ascribed to changes to lecithinization-induced biodistribution, antioxidative activity and cytotoxicity.
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PMID:Lecithinized ascorbic acid (PC-AS) effectively inhibits murine pulmonary metastasis. 1036 58