Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Differences in the incidence of adverse drug reactions to trimethoprim-sulfamethoxazole and dapsone may result from differences in the formation, disposition, toxicity, and/or detoxification of their hydroxylamine metabolites. In this study, we examine whether differences in the biochemical processing of sulfamethoxazole hydroxylamine (SMX-NOH) and dapsone hydroxylamine (DDS-NOH) by erythrocytes [red blood cells (RBCs)] contribute to this differential incidence. The methemoglobin (MetHgb)-forming capacity of both metabolites was compared after a 60-min incubation with washed RBCs from four healthy human volunteers. DDS-NOH was significantly more potent (P =.004) but equally efficacious with SMX-NOH in its ability to form MetHgb. The elimination of potential differences in disposition by lysing RBCs did not change the MetHgb-forming potency of either hydroxylamine. At pharmacologically relevant concentrations, greater reduction to the parent amine occurred with DDS-NOH. Maintenance of MetHgb-forming potency was dependent on recycling with glutathione, but no difference in cycling efficiency was observed between DDS-NOH and SMX-NOH. In contrast, the pharmacodynamics of hydroxylamine-induced MetHgb formation were not changed by pretreatment with the glucose 6-phosphate dehydrogenase inhibitor epiandrosterone or by compounds that alter normal antioxidant enzyme activity. Methylene blue, which stimulates NADPH-dependent MetHgb reductase activity, decreased MetHgb levels but did not alter the differential potency of these hydroxylamines. DDS-NOH was also significantly more potent when incubated with purified human hemoglobin A0. Collectively, these data suggest that the inherently greater reactivity of DDS-NOH with hemoglobin, the greater conversion of DDS-NOH to its parent amine, and potential differences in disposition of hydroxylamine metabolites may contribute to the preferential development of dapsone-induced hemotoxicity and sulfamethoxazole-induced hypersensitivity reactions.
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PMID:Methemoglobin formation by hydroxylamine metabolites of sulfamethoxazole and dapsone: implications for differences in adverse drug reactions. 1002 31

It is well known that antioxidants and reactive oxygen species play an important role in carcinogenesis. In this study, we attempted to evaluate antioxidant enzyme activities and lipid peroxidation levels in cancerous bladder tissue and to determine their relationship with bacterial infection. Bacterial culture was made from all urine samples using Blood and Eosin Methylene Blue agars for checking the presence of bacterial infections. We measured thiobarbituric acid reactive substances (TBARs) and activities of xanthine oxidase (XO), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and catalase (CAT) in cancerous tissues of 25 bladder cancer patients, in noncancerous adjacent bladder tissues of 13 out of these 25 patients, and in control bladder tissues of 15 patients with a non-neoplastic genitourinary disease. TBARs levels increased and XO, SOD, GSH-PX, and CAT activities decreased significantly in cancerous bladder tissues. TBARS, XO, and SOD levels were not significantly different between noncancerous adjacent tissue and control bladder tissue. Statistically significantly lower GSH-PX and higher CAT activities were observed in noncancerous adjacent bladder tissue compared with cancerous tissue. GSH-PX level of tumor tissue was correlated significantly with tumor grade (r=-0.425, P=0.034). Results suggested that pathway activity of free radicals were accelerated in the cancerous human bladder tissues via increased TBARs levels and decreased enzyme activities of XO, SOD, GSH-PX, and CAT, which implicated a severe exposure of cancerous tissues to oxidative stress.
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PMID:Lipid peroxidation and antioxidant enzyme activities in cancerous bladder tissue and their relation with bacterial infection: a controlled clinical study. 2008 49