Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of ethylene glycol (EG) on the hepatic drug metabolizing enzymes. The exposed group was given 1% EG solution and the control group was provided with distilled water for 2 weeks ad libitum. The body weight of the exposed group was the same as that of the control group. The liver and kidney weight per body weight did not change. The daily drinking volume for the exposed group on the average showed an increase of 13.5% over that of the control group. Hematologically and biochemically, anemia, liver and renal dysfunction were not seen. The content of the hepatic microsomal cytochrome P-450 in the exposed group showed an increase of 17% over that of the control group, but the contents of cytochrome b5, protoheme and the activities of NADPH-cytochrome c reductase, NADH-ferricyanide reductase did not change. The activities of the hepatic cytosolic alcohol dehydrogenase and glutathione reductase, glutathione peroxidase, glutathione-S-transferase also did not change. These results indicate that the hepatic microsomal cytochrome P-450 takes part in the metabolism of EG.
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PMID:[Effects of ethylene glycol on drug metabolizing enzymes in rat liver]. 202 9

The effects of chronic ethylene oxide (EtO) inhalation on porphyrin-heme metabolism were investigated. When Wistar male rats were exposed to 500 ppm EtO for 6 h a day, 3 times a week for 13 weeks, hemoglobin content significantly decreased, and a normocytic and normochromic anemia was found. In the liver, cytochrome P-450 and protoheme significantly decreased but wet weight, microsomal protein and cytochrome b5 were not affected. The activity of delta-aminolevulinic acid (ALA) synthase increased while ALA dehydratase did not change. The activity of hepatic ferrochelatase decreased time-dependently. Uroporphyrin increased 37% and coproporphyrin tended to increase in the liver. The concentration of protoporphyrin in the liver and erythrocytes tended to increase. Coproporphyrin excretion in the urine showed a 5-6-fold increase while there was no significant increase in urinary ALA excretion. These results indicate that chronic inhalation of EtO causes alterations of hepatic porphyrin-heme metabolism as well as anemia and may affect mechanisms of adaptation to xenobiotics.
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PMID:Chronic inhalation effects of ethylene oxide on porphyrin-heme metabolism. 231 47

1. Primaquine (PQ) often causes severe anaemia in individuals with glucose 6-phosphate dehydrogenase (G6PD) deficient erythrocytes, and metabolites have been implicated as the toxic substance. These studies present data identifying additional metabolites of PQ. 2. Two metabolites of primaquine (PQ) previously identified in human studies, namely, 6-methoxy-8-aminoquinoline (MAQ) and 8-(3-carboxy-1-methylpropylamino)-6-methoxyquinoline (PQC) were also formed on incubation of PQ with hamster liver fractions for up to 24 h without an NADPH-generating system. 3. The alcohol (PQAOH) and lactam (PQLT) derivatives of PQ were also formed on incubation with hamster liver fraction used in these studies. 4. The microsomal metabolism of PQ was decreased in presence of an NADPH-generating system, but not by SKF-525A or glutathione (GSH) indicating that the oxidative reactions were probably not due to the cytochrome P-450 system or free radical mechanisms.
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PMID:Effects of an NADPH-generating system on primaquine degradation by hamster liver fractions. 324 12

The changes in the cytochrome P-450 enzyme system of rat liver, lung and brain after inhalation of ethylene oxide were studied. When Wistar male rats were exposed to 500 ppm ethylene oxide three times a week for three months, they showed a suppressed gain of body weight. Therefore, the present study was done using pair-fed rats. Haematological examination revealed normocytic and normochromic anemia. Liver and renal functions were normal. The cytochrome P-450 enzyme system in the lung and brain were not affected. However, hepatic cytochrome P-450 and protoheme decreased by 28% and 19%, respectively. Hepatic total microsomal protein, cytochrome b5, NADPH-cytochrome c reductase and NADH-ferricyanide reductase were not affected. The activity of hepatic heme oxygenase showed a 2-fold increase. These results suggest that the heme moiety of hepatic cytochrome P-450 was primarily attacked by exposure of ethylene oxide and the cellular heme balance in liver was altered.
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PMID:[Effects of chronic exposure of ethylene oxide, especially on heme metabolism]. 336 71

Observations on the interactions of cadmium (Cd) x aflatoxin B1 (AFB1) and Cd x warfarin included several variables of animal performance and hematology. Cadmium was fed daily for 40 days (groups IV, V, VI) and a Cd-free diet was fed to groups I, II, and III. Groups II and V were treated with AFB1, and groups III and VI were treated with warfarin--each for 5 days during the 5th week of the experiment and the effects were observed for 10 days. All pigs fed the diet with added Cd had developed severe anemia by the 4th week of the experiment. The incorporation of this toxic concentration of Cd (83 micrograms/g) in the diet seemed to have blocked the liver microsomal enzyme system (cytochrome P-450), diminishing the toxic effects of 5 daily oral doses (0.2 mg/kg of body wt) of AFB1 (group V pigs), but enhancing synergistically the toxic anticoagulant effects of the same doses of warfarin in young pigs (group VI). The data presented also indicated that the feeding of toxic concentrations of Cd stimulated increased glutathione peroxidase activity, which conjugated the AFB1 epoxides with their excretion as reduced glutathione but enhanced the toxic anticoagulant effects of warfarin in young pigs.
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PMID:Toxicology of aflatoxin B1, warfarin, and cadmium in young pigs: performance and hematology. 680 73

The molecular defect of the hereditary disease Fanconi anemia (FA) remains unknown. The two theoretical possibilities are (1) an impaired DNA crosslink-repair system or (2) a disturbed oxygen metabolism either by overproduction of reactive oxygen intermediates (ROI) or by diminished detoxification of ROI. In order to gain further insight into the molecular mechanism of this disease, we have determined the repair capacity of FA cells challenged by crosslinking agents and have analyzed diverse biological systems that are involved in oxygen metabolism. We have tested normal and FA cells for oxygen consumption and for the activity of the antioxidant phospholipid-hydroperoxide-glutathione-peroxidase (PHGPx). FA cells show a reduced oxygen consumption and an increased PHGPx activity. Since spontaneous and induced chromosomal instability is a main cellular feature of FA, we have analyzed the redox state of cells and the effect of cytochrome P-450 (Cyt P-450) inhibitors and inducers on chromosomal breaks and micronuclei production. Our results indicate that Cyt P-450 enzymes, especially Cyt P-450 1A2, play a crucial role in radical metabolism in FA cells. Furthermore, we have determined NF-kappa B activity in untransformed cells and in SV40-transformed cells by gel shift experiments. NF-kappa B is a multiunit transcription factor that is known to be induced by ROI and that activates the expression of various genes involved in cellular responses to stress. NF-kappa B is constitutively induced in SV40-transformed FA cells probably as a consequence of an increased ROI level. Our results suggest that enzymatic defects in oxygen metabolism mediate the FA phenotype via impaired reactivity with ROI. Cyt P-450 1A2 appears to be a good candidate for the defective enzyme, even though no differences have been measured in the activity of this enzyme in FA and control fibroblasts in pilot experiments.
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PMID:The role of oxygen metabolism for the pathological phenotype of Fanconi anemia. 918 62

Fanconi anaemia (FA) is a cancer-prone genetic disorder that is characterised by cytogenetic instability and redox abnormalities. Although rare subtypes of FA (B, D1 and D2) have been implicated in DNA repair through links with BRCA1 and BRCA2, such a role has yet to be demonstrated for gene products of the common subtypes. Instead, these products have been strongly implicated in xenobiotic metabolism and redox homeostasis through interactions of FANCC with cytochrome P-450 reductase and with glutathione S-transferase, and of FANCG with cytochrome P-450 2E1, as well as redox-dependent signalling through an interaction between FANCA and Akt kinase. We hypothesise that FA proteins act directly (via FANCC and FANCG) and indirectly (via FANCA, BRCA2 and FANCD2) with the machinery of cellular defence to modulate oxidative stress. The latter interactions may co-ordinate the link between the response to DNA damage and oxidative stress parameters (3, 6-12).
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PMID:Fanconi anaemia proteins: major roles in cell protection against oxidative damage. 1276 48

Methaemoglobinaemia is an uncommon problem which can significantly impact on oxygen carriage and may necessitate intensive care management. The occurrence of symptomatic methaemoglobinaemia over a three-month period in four patients with haematological malignancies on dapsone for Pneumocystis jiroveci pneumonia prophylaxis prompted a review of its use in this group of patients. We performed a retrospective audit to identify any contributing factors. Co-oximetry was employed to identify patients with methaemoglobinaemia. Thirty-four patients with haematological malignancies received dapsone between January and December 2008, of whom 53% (n = 18) had co-oximetry studies done. Raised methaemoglobin levels (> or = 1.5%) were seen in 13 patients, four of them symptomatic. Mean peak level was of 7.84% (range 1.9 to 26.8%). Eight patients required intensive care support. Mean onset of methaemoglobinaemia was 11.8 days (range 4 to 18 days) following dapsone commencement. All patients were anaemic with an average haemoglobin of 85.5 g/l (range 59 to 111 g/l). All patients were prescribed 'azole' antifungal agents and five patients were also on high-dose steroids, both agents known to induce cytochrome P-450 enzymes and hence potentiating dapsone toxicity. Our experience suggests that dapsone should be used with caution in patients with haematological malignancies as they are particularly at risk of developing symptomatic methaemoglobinaemia due to underlying anaemia, immunosuppression and potential drug interactions. The current recommendation of dapsone for Pneumocystis jiroveci pneumonia prophylaxis in this group of patients needs to be reviewed. When methaemoglobinaemia does occur early recognition is possible with routine co-oximetry testing and prompt treatment may lessen the need for or duration of intensive care supports.
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PMID:Dapsone-associated methaemoglobinaemia in patients with a haematologic malignancy. 2122 40

The effect of 6 MFA (Sixth mycelial fraction of acetone), an interferon inducer obtained from fungus Aspergillus ochraceus, on rifampicin toxicity was studied in rats. Chronic oral administration of rifampicin (1 g/kg per day) for 30 days produced thrombocytopenia, hemolytic anaemia, transient leukopenia and increased nucleated cells in bone marrow and decreased weights of thymus and spleen significantly in male rats. Furthermore, chronic administration of rifampicin induced significant increase in cytochrome P-450 contents, lipid peroxidation (LPO) and superoxide dismutase (SOD) activity in liver and bone marrow. Simultaneous administration of 6 MFA (100 mg/kg; i.p.) on alternate days for a period of 30 days prevented most of the adverse effects of rifampicin, mentioned earlier and also restored the hepatic architecture histologically. The LPO, cytochrome P 450 content, lymphocyte and bone marrow cell counts returned to normal level whereas SOD activity was further increased. The 6 MFA treatment enhanced the SRBC antibody litre in rifampicin-treated rats. Thus, beneficial effects of 6 MFA in the amelioration of mediated rifampicin toxicity observed in the present study may be through induction of interferons and their associated effects.
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PMID:Modulation of rifampicin toxicity by 6 MFA, an interferon inducer obtained from fungus Aspergillus ochraceus. 2178 70

Peripheral T-cell lymphoma is a heterogenous non-Hodgkin Lymphoma with historically poor outcomes. Currently, response rates remain poor with traditional chemotherapy and many of those responding to initial therapy will relapse. Belinostat (Beleodaq, Spectrum Pharmaceuticals) is a histone deacetylase inhibitor (HDACi) approved for use in relapsed or refractory peripheral T-cell lymphoma (PTCL). Belinostat is metabolized hepatically through cytochrome P-450 enzymes 3A4, 2C9, and 2A6; however, no empiric dosage adjustments of belinostat are recommended during concurrent use of inhibitors or inducers of these enzymes. Belinostat's efficacy has been evaluated in a clinical trial showing an overall response rate (ORR) of 25.8% and a median duration of response of 8.4 months. Belinostat is generally well tolerated, with the most common adverse reactions (>25%) being nausea, vomiting, fatigue, pyrexia, and anemia in patients with relapsed or refractory PTCL. Belinostat is a safe and effective treatment option for relapsed and refractory peripheral T-cell lymphoma, with many future applications currently being investigated.
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PMID:Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma. 2692 Oct 86


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