dicumarol and Anemia--Hemolytic

The enzyme DT-diaphorase catalyses the 2-electron reduction of quinones. This reaction may facilitate the detoxification of such compounds, since the hydroquinone so formed can be converted into non-toxic conjugates. There is evidence for the involvement of DT-diaphorase in the detoxification of menadione (2-methyl-1,4-naphthoquinone) in a wide range of cells and tissues in vitro, but no information is available on the possible influence of this enzyme on the harmful effects of menadione in vivo. In animals, menadione is selectively toxic to erythrocytes, causing haemolytic anaemia. In the present study, rats were treated with dicoumarol, an inhibitor of DT-diaphorase, or butylated hydroxyanisole (BHA), a substance that increases the activity of this enzyme in vivo. They were then challenged with a toxic dose of menadione. Dicoumarol increased the severity of menadione-induced haemolytic anaemia while BHA decreased it, consistent with a role for DT-diaphorase in the detoxification of menadione in vivo, as previously described in vitro.

Topics: Anemia, Hemolytic; Animals; Antioxidants; Butylated Hydroxyanisole; Dicumarol; Dihydrolipoamide Dehydrogenase; Enzyme Inhibitors; Erythrocytes; Female; Heinz Bodies; Hemolysis; Hemostatics; Liver; NAD(P)H Dehydrogenase (Quinone); Organ Size; Rats; Rats, Sprague-Dawley; Spleen; Vitamin K

Ferrokinetic studies in two patients with haemolytic anaemia due to haemoglobin Wien revealed increased haemoglobin synthesis and an increase in effective erythropoiesis. Haemolysis is due to an instability of the haemoglobin itself. The spleen does not appear to play any appreciable role in the aetiology of this condition. There was no extramedullary erythropoiesis in our patients.

Topics: Adolescent; Adult; Anemia, Hemolytic; Dicumarol; Erythropoiesis; Female; Hemoglobins, Abnormal; Humans; Iron; Lung; Male; Pulmonary Embolism; Radionuclide Imaging; Spleen

Topics: Anemia, Hemolytic; Antipyrine; Dicumarol; Genes; Genetics, Medical; Humans; Hydralazine; Metabolism, Inborn Errors; Pharmaceutical Preparations; Pharmacogenetics; Pharmacology; Phenelzine; Phenylbutazone; Sulfamethazine