Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chagas' disease (American trypanosomiasis) is an endemic parasitic disease in some areas of Latin America. About 16-18 million persons are infected with the aetiological agent of the disease, Trypanosoma cruzi, and more than 100 million are living at risk of infection. There are different modes of infection: (1) via blood sucking vector insects infected with T. cruzi, accounting for 80-90% of transmission of the disease; (2) via blood transfusion or congenital transmission, accounting for 0.5-8% of transmission; (3) other less common forms of infection, eg, from infected food or drinks or via infected organs used in transplants. The acute phase of the disease can last from weeks to months and typically is asymptomatic or associated with fever and other mild nonspecific manifestations. However, life-threatening myocarditis or meningoencephalitis can occur during the acute phase. The death rate for persons in this phase is about 10%. Approximately 10-50% of the survivors develop chronic Chagas' disease, which is characterized by potentially lethal cardiopathy and megacolon or megaoesophagus. There are two drugs available for the aetiological treatment of Chagas' disease: nifurtimox (Nfx) and benznidazole (Bz). Nfx is a nitrofurane and Bz is a nitroimidazole compound. The use of these drugs to treat the acute phase of the disease is widely accepted. However, their use in the treatment of the chronic phase is controversial. The undesirable side effects of both drugs are a major drawback in their use, frequently forcing the physician to stop treatment. The most frequent adverse effects observed in the use of Nfx are: anorexia, loss of weight, psychic alterations, excitability, sleepiness, digestive manifestations such as nausea or vomiting, and occasionally intestinal colic and diarrhoea. In the case of Bz, skin manifestations are the most notorious (e.g., hypersensitivity, dermatitis with cutaneous eruptions, generalized oedema, fever, lymphoadenopathy, articular and muscular pain), with depression of bone marrow, thrombocytopenic purpura and agranulocytosis being the more severe manifestations. Experimental toxicity studies with Nfx evidenced neurotoxicity, testicular damage, ovarian toxicity, and deleterious effects in adrenal, colon, oesophageal and mammary tissue. In the case of Bz, deleterious effects were observed in adrenals, colon and oesophagus. Bz also inhibits the metabolism of several xenobiotics biotransformed by the cytochrome P450 system and its reactive metabolites react with fetal components in vivo. Both drugs exhibited significant mutagenic effects and were shown to be tumorigenic or carcinogenic in some studies. The toxic side effects of both nitroheterocyclic derivatives require enzymatic reduction of their nitro group. Those processes are fundamentally mediated by cytochrome P450 reductase and cytochrome P450. Other enzymes such as xanthine oxidoreductase or aldehyde oxidase may also be involved.
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PMID:Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis). 1693 19

The root bark of Anisophyllea dichostyla R. Br. is traditionally used in the Democratic Republic Congo for the treatment of several conditions such as anorexia, fatigue and intestinal infections. We have identified and quantitated several polyphenol antioxidants in the methanol extract of the root bark (120g). The polyphenol content (3.32g/kg) was predominantly ellagitannins (25%) and polyhydroxyflavan-3-ols (catechins and procyanidins, 75%) with 3'-O-methyl-3,4-methylenedioxo ellagic acid 4'-O-beta-d-glucopyranoside and (-)-epicatechin as the major species in each class. These two compounds and the following species were identified unequivocally by NMR spectroscopy: (+)-catechin, (-)-epicatechin 3-O-gallate, 3-O-methyl ellagic acid, 3,3'-di-O-methyl ellagic acid, 3'-O-methyl-3,4-methylenedioxo ellagic acid, 3'-O-methyl-3,4-methylenedioxo ellagic acid 4'-O-beta-d-glucopyranoside, and 3'-O-methyl ellagic acid 4-O-beta-d-xylopyranoside. The following additional compounds were purified by semi-preparative HPLC and tentatively identified on the basis of UV spectra, HPLC-ESI-MS and nano-ESI-MS-MS: (+)-catechin-3-O-beta-d-glucopyranoside, epicatechin-(4beta-->8)-catechin (procyanidin B(1)), epicatechin-(4beta-->8)-epicatechin (procyanidin B(2)), an (epi)catechin trimer, 3-O-methyl ellagic acid 4-O-beta-d-glucopyranoside, (-)-epicatechin 3-O-vanillate, 3,4-methylenedioxo ellagic acid 4'-O- beta-d-glucopyranoside, and 3,3'-di-O-methyl ellagic acid 4-O-beta-d-xylopyranoside. Fractionation of the raw extract by column chromatography on silicic acid yielded 10 fractions. In the hypoxanthine/xanthine oxidase antioxidant assay system, CC-9 which contained a range of polyphenols dominated by (-)-epicatechin-O-gallate proved to be the most potent antioxidant fraction (IC(50)=52 micro g/mL) in terms of ROS scavenging. In terms of XO inhibition CC-8, dominated by (epi)catechin trimer and which also contained appreciable amounts of 3'-O-methyl ellagic acid 4'-O-beta-d-xylopyranoside, as well as the catechins (+)-catechin-3-O-beta-d-glucopyranoside, epicatechin-(4beta-->8)-catechin (procyanidin B(1)), and (-)-epicatechin 3-O-gallate, proved to be the most potent (IC(50)=36 micro g/mL).
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PMID:Isolation, purification and identification of ellagic acid derivatives, catechins, and procyanidins from the root bark of Anisophyllea dichostyla R. Br. 1708 99

Cancer cachexia is a systemic wasting syndrome characterized by anorexia and loss of body weight. The xanthine oxidase (XO) inhibitor febuxostat is one of the promising candidates for cancer cachexia treatment. However, cachexic symptoms were not alleviated by oral administration of febuxostat in our cancer cachexia model. Metabolomic analysis with brains of our cachexic model showed that purine metabolism was activated and XO activity was increased, and thus suggested that febuxostat would not reach the brain. Accordingly, targeting XO in the brain, which controls appetite, may be an effective strategy for treatment of cancer cachexia.
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PMID:A novel strategy for treatment of cancer cachexia targeting xanthine oxidase in the brain. 3115 93