Atividade da NADH-redutase de metemoglobina em hemolisado e membranas eritrocitarias de pacientes hansenianos sob tratamento sulfonico

AUTOR(ES)
DATA DE PUBLICAÇÃO

1997

RESUMO

We measured in the blood samples of 72 adults leprosy patients who were ingesting 100 mg of dapsone/day, the levels of erythrocytes, hemoglobin, methemoglobin, sulfone and reticulocytes. NADH-methemoglobin reductase was measured in the hemolysate and ghost cells. AlI subjects were impatients of Instituto Lauro de Souza Lima - Bauru S.P. Brazil. IdenticaI tests, except sulfone were applied in the blood samples of 72 heaIthy individuais that not ingested oxidant drugs. The means of the erythrocytes, hemoglobin,hematocrit and hematological indexes were among patients lower than healthy individuais, what is due to the hemolytic effect of dapsone. An important mechanism for oxidant drug-induced hemolysis is because some of these drugs generate hydrogen peroxide by their reaction with hemoglobin17. The mean levei of methemoglobin in the leprosy patients was higher than in the control group, ando it s also due to the action of dapsone, which has great potentiaI to cause an increased methemoglobin level5O. A balance between the oxidation and reduction of heme iron determines the levei of methemoglobin in erythrocytes. The NADH cytochrome bs reductase of the erythrocytes reduced the ferric cytochrome b s generated from nonenzymatically reduction of methemoglobin by ferrous form of cytochrome bs 72. In this work we measured NADH-reductase activity in he1110lysate and intact ghost cell of the leprosy patients who were ingesting dapsone. The enzimatic activity was determined by spectrophotometric assays as previously described by Scott73, with slight modifications. We incubated the washed erythrocytes for 30 minutes in a solution containing 1 % (wt/vol) NaNOz 67. The erythrtocyte ghosts were prepared according to Dodge et at21. The mean enzyme activity..in the hemolysate of the leprosy patients and the healthy individuaIs has not differed significantly when expressed in UI/gr.Hemoglobin/l, but the mean enzyme actiyity in erythrocytes ghost from leprosy patients was significantly smaIler then that erythrocyte ghosts ITom healthy individuais. The present observation may be explained by the increased leveI of methemoglobin in the erythrocyte citoplasm of the patients. The consumptiom of the NADH-reductase is increased and the erythrocytes did not produce more enzymes becaus"e that cell during the maturation stages develops extrusion of its nucleus and decrease it s number of ribosomes (cytoplasmic organelles) where this enzyme is likely produced6. The NADH-methemoglobin reductase reduces cytochrome bs, which converts non-enzymically methemoglobin into hemoglobin83.. Hultquist et aI, 1974, suggest the microssomal origin of this protein by comparing the trypsin-digest cytochrome b5 of erythrocytes with trypsin solubilized cytochrome b5 from human liver microssomes72. The cytochrome b5 and NADH-cytochrome b5 reductase, which constitute the methemoglobin reducing system of mature human erythrocytes, originate from the endoplasmic reticulum of nuc1eated red cell precursors. The solubilizing agent is possibly a protease provided by lysosomes of the immature red cells 72. It s us therefore likly that leprosy patients, the consuption of erythrocyte membrane and soluble cytoplasmic NADH-reductase enzyme is increased due to raising of the methemoglobin leveI. The membrane NADH-reductase enzyme is a precursor form of the soluble cytoplasm enzyme and both are regulated by a similar related genetic control mechanism43. Dapsone promotes the increase in enzyme activity in the supernatant of ghost suspension after treatment with the drug, and was dependent on Dapsone concentration4

ASSUNTO(S)

hanseniase metoglobinemia membrana eritrocitica

ACESSO AO ARTIGO

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