vitamin-k-semiquinone-radical and Hemolysis

Topics: Adult; Altitude; Bilirubin; Biological Transport; Erythrocyte Aging; Female; Hemolysis; Hepatitis B; Hexosyltransferases; Humans; Hyperbilirubinemia; Hyperbilirubinemia, Hereditary; Infant, Newborn; Jaundice; Liver; Novobiocin; Portacaval Shunt, Surgical; Pregnancy; Vitamin K

Topics: Albumins; Bilirubin; Blood Transfusion, Intrauterine; Erythrocytes; Exchange Transfusion, Whole Blood; Female; Hemolysis; Humans; Infant, Newborn; Jaundice, Neonatal; Kernicterus; Liver; Phenobarbital; Phototherapy; Pregnancy; Protein Binding; Serum Albumin; Vitamin K

Topics: Animals; Animals, Newborn; Hemolysis; Humans; Hyperbilirubinemia; Vitamin K

Topics: Abnormalities, Drug-Induced; Anti-Bacterial Agents; Anticoagulants; Antimetabolites; Antineoplastic Agents; Antithyroid Agents; Female; Fetal Diseases; Fetus; Hemolysis; Hormones; Humans; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Pregnancy; Reserpine; Salicylates; Thalidomide; Tolbutamide; Vitamin K

A phase I study of mitomycin C with menadione (2-methyl-1,4-naphthoquinone, a vitamin K analogue which lowers intracellular pools of reduced glutathione) was designed as an approach to overcoming tumor cell resistance to alkylating agent chemotherapy. Patients with refractory solid tumors (n = 51) were treated with a 48-h continuous intravenous infusion of menadione followed by a bolus intravenous dose of mitomycin C at the completion of the menadione infusion. Initial menadione doses of 8.0 and 4.0 g/m2 over 48 h were associated with hemolysis, so subsequent dose levels of menadione ranged from 1.0 to 3.0 g/m2 with mitomycin C from 5 to 20 mg/m2. All three patients treated with menadione at 8.0 g/m2 and the single patient treated at 4.0 g/m2 with mitomycin C at 5 mg/m2 developed clinically significant hemolysis despite the presence of red blood cell glucose-6-phosphate dehydrogenase. Subsequently, a revised escalation scheme for menadione was used, and all patients tolerated menadione doses of 1-2.5 g/m2 over 48 h with mitomycin C doses up to 20 mg/m2. Since the 3.0 g/m2 dose of menadione was associated with mild hemolysis in three of four patients, the maximum tolerated dose of menadione was established at 2.5 g/m2. All of the mitomycin dose levels were tolerated without unexpected toxicities attributable to the combination. Prolonged infusions of menadione at doses which have been associated with lowering of intracellular glutathione pools in short-term exposure are limited by dose-dependent hemolysis, probably due to depletion of erythrocyte glutathione by menadione-related redox cycling. There was no detectable deleterious effect of pre-exposure to menadione on mitomycin C tolerance. We recommend a combination of menadione at 2.5 g/m2 as a continuous intravenous infusion and mitomycin C at 15 mg/m2 for further study in solid tumors, for which treatment with single-agent mitomycin C is appropriate.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Erythrocytes; Female; Glucosephosphate Dehydrogenase; Glutathione; Hemolysis; Humans; Infusions, Intravenous; Male; Middle Aged; Mitomycin; Neoplasms; Vitamin K

Our study was designed to evaluate, on healthy subjects and patients on oral anticoagulant therapy vitamin K antagonist (OAT-vka), the possible interference caused by hemolysis on the main coagulation tests.. To obtain hemolyzed samples, two methods were used: heat shock and mechanical system. The coagulation tests on hemolyzed samples were performed employing optical automated analyser BCSxp (Siemens Healthcare(®)). Moreover, the prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests were also carried out manually using an electromechanical device (KC4 - Amelung).. The PT test, on healthy subjects, in case of moderate hemolysis can be performed without significant interference on automatic instrument. On manual instrument, the PT test can be performed even in case of marked hemolysis. For patients on OAT-vka, the PT test in case of marked hemolysis can be performed both on automatic and manual instrument. For the aPTT test, it can be carried out manually, because also in case of marked hemolysis a statistically significant difference was not observed. For the fibrinogen test, a dramatic concentration decrease was already clear for weak hemolysis. A decreased function on antithrombin test was statistically significant for mild-moderate hemolysis. The D-dimer test showed increased values for mild hemolysis.. The rejection of hemolyzed sample and/or the request of a second sample are not always the proper attitudes to take for performing clotting tests. The rational management of the hemolyzed samples decreases the employment of both nursing and technical staff significantly, the turnaround time and, consequently, does not lead to additional costs for each patient involved.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Erythrocyte Indices; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Healthy Volunteers; Hemolysis; Humans; Male; Partial Thromboplastin Time; Prothrombin Time; Vitamin K

Individuals with celiac disease (CD) are predisposed to a number of haematological abnormalities including anaemia secondary to malabsorption of iron, vitamin B12 or folate; anaemia of chronic disease and coagulopathy secondary to vitamin K deficiency. Correction of coagulopathy with vitamin K is necessary before endoscopic biopsy in patients with suspected CD. However, vitamin K causes haemolysis in glucose-6 phosphate-dehydrogenase deficiency.. When vitamin K administration becomes necessary for correction of coagulopathy in patients with CD; glucose-6 phosphate-dehydrogenase deficiency should be considered.

Topics: Celiac Disease; Contraindications; Diet, Gluten-Free; Endoscopy, Gastrointestinal; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Infant; Intestinal Mucosa; Male; Vitamin K; Vitamin K Deficiency

Topics: Adult; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Male; Textbooks as Topic; Vitamin K

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

Staphylococcus aureus menadione and hemin auxotrophs, generated by in vitro gentamicin selection, demonstrated reduced hemolytic activity and enhanced intracellular survival within cultured bovine aortic endothelial cells relative to their hemolytic parent. Supplementation of the auxotrophs with exogenous menadione or hemin resulted in rapid growth, increased hemolytic activity, and reduced intracellular persistence to the level found for the hemolytic clinical parent. Aminoglycoside selection of staphylococcal menadione and hemin auxotrophs and subsequent persistence of these variants in the intracellular milieu may adapt S. aureus for evasion of host defenses and resistance to antimicrobial therapy.

Topics: Animals; Aorta; Cattle; Cells, Cultured; Drug Resistance, Microbial; Endothelium, Vascular; Gentamicins; Hemin; Hemolysis; Humans; Phagocytosis; Rabbits; Staphylococcus aureus; Vitamin K

Species differences in red blood cell susceptibility to the photohemolytic agents chlorpromazine, menadione and tetracycline were examined in mouse, rat, dog, and human blood. Menadione and tetracycline (25 microM) hemolyzed mouse but not dog, rat, or human red blood cells (RBC) when irradiated with UV light but not in the dark. Chlorpromazine (25 microM) produced a photohemolytic response in all four species with mouse and rat RBC lysing fastest followed by human then dog cells. Investigations into the nature of these species differences suggested that the size of mouse RBC may contribute to its high sensitivity to photohemolytic agents. An investigation of the effect of UV light on key antioxidant enzymes revealed species differences in enzyme inactivation. These data suggest that mouse RBC may be particularly vulnerable to phototoxic agents, especially those compounds which produce active oxygen species and, therefore, may prove more useful than human RBC as a model for predicting phototoxic potential of some chemical entities.

Topics: Animals; Chlorpromazine; Dogs; Erythrocytes; Free Radical Scavengers; Hemolysis; Humans; In Vitro Techniques; Mice; Photochemistry; Rats; Species Specificity; Tetracycline; Ultraviolet Rays; Vitamin K

The short-term toxicity of 2-hydroxy-1,4-naphthoquinone (lawsone) and 2-methyl-1,4-naphthoquinone (menadione) has been compared in rats. 2-Methyl-1,4-naphthoquinone has been shown previously to cause haemolytic anaemia in animals, and this was confirmed in the present experiment. 2-Hydroxyl-1,4-naphthoquinone was found also to cause haemolysis, in a dose-dependent manner, as reflected by decreased blood packed cell volumes and haemoglobin levels and by histopathological changes in spleen, liver and kidney. With both naphthoquinones, the haemolysis was of the oxidative type, characterized by the presence of Heinz bodies within erythrocytes. Haemolysis was the only toxic change identified in rats dosed with 2-methyl-1,4-naphthoquinone. In contrast, 2-hydroxyl-1,4-naphthoquinone was not only a haemolytic agent but also a nephrotoxin, causing renal enlargement, elevated plasma levels of urea and creatinine and histologically-identified tubular necrosis, largely confined to the distal segment of the proximal convoluted tubules. The relationship between the in vivo toxic effects of these naphthoquinones and previously-reported data on their in vitro cytotoxic action is discussed.

Topics: Animals; Female; Hemolysis; Kidney Diseases; Naphthoquinones; Rats; Rats, Inbred Strains; Time Factors; Vitamin K

Hemoglobin in glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes is abnormally vulnerable to oxidative denaturation, which may release ferriheme, a known cytolytic agent. We found 13.3 nmol of ferriheme in G6PD-deficient erythrocyte membranes (per gram of total erythrocyte hemoglobin) using a spectrophotometric assay, as compared to 9.8 in normal membranes (P less than .05). After incubation of erythrocytes with 250 mumol/L menadione, an oxidant drug, the values increased by 37.4 nmol in G6PD-deficient membranes and by 26 in normal membranes (P less than .005), indicating increased hemoglobin denaturation. To verify that hemoglobin denaturation in G6PD-deficient erythrocytes releases ferriheme in a form available to interact with other ligands, [14C]-chloroquine binding to intact erythrocytes was measured. With an initial concentration of 5 mumol/L chloroquine in a medium containing no menadione, an excess of 14.8 nmol of chloroquine was bound in G6PD-deficient erythrocytes (per gram of hemoglobin) as compared to normal erythrocytes (P less than .005). In the presence of 250 mumol/L menadione, chloroquine binding increased by 17.9 nmol in G6PD-deficient and by 7.2 in normal erythrocytes (P less than .005). These results indicate that ferriheme becomes available to interact with endogenous ligands and, thus, to mediate menadione-induced hemolysis in patients with G6PD deficiency. Furthermore, the increase in ferriheme may mediate the selective toxicity of menadione for Plasmodium falciparum parasites growing in G6PD-deficient erythrocytes. Ferriheme release in response to the intraerythrocytic oxidant stress introduced by malaria parasites also may account for the resistance to malaria afforded by G6PD deficiency. This is a US government work. There are no restrictions on its use.

Topics: Chloroquine; Erythrocyte Membrane; Ferric Compounds; Glucosephosphate Dehydrogenase Deficiency; Heme; Hemolysis; Humans; Malaria; Male; Vitamin K

Ferriprotoporphyrin IX (FP) is released from hemoglobin by oxidative denaturation or by proteolytic degradation. FP added exogenously to cells or released intracellularly is a lytic toxin. Chloroquine enhances the accumulation of exogenous FP in cellular membranes and potentiates its lytic effect. Menadione is an example of an oxidant drug that denatures hemoglobin, releases FP intracellularly, and thereby lyses cells. Chloroquine increases the accumulation of FP in the membranes of menadione-treated erythrocytes and enhances the hemolysis induced by menadione. Intraerythrocytic malaria parasites release FP from hemoglobin by proteolytic degradation, but they ordinarily survive the exposure either because FP interacts with a soluble intracellular substance, which renders it nontoxic, or because FP is sequestered in an innocuous, insoluble form in malaria pigment. Chloroquine binds tightly to FP, diverts it away from the soluble detoxifying substance in malaria parasites, and delays its sequestration into malarial pigment. Malaria parasites exposed to chloroquine while degrading hemoglobin accumulate a chloroquine-FP complex, which is sufficiently toxic to kill them. FP has a detergent-like effect on biological membranes which may account for its lytic toxicity.

Topics: Aminoquinolines; Animals; Antimalarials; Cell Membrane; Chloroquine; Erythrocytes; Heme; Hemin; Hemolysis; Malaria; Oxidation-Reduction; Plasmodium berghei; Rabbits; Vitamin K

Human erythrocytes were treated with menadione to oxidatively denature hemoglobin and release ferriprotoporphyrin IX (ferriheme, FP) intracellularly. The high affinity of FP for chloroquine was used to detect its release. After incubation for 1 hr at 37 degrees C and pH 7.4 with 0.5 mM menadione, erythrocytes bound 14C-chloroquine with an apparent dissociation constant of 10(-6)M. Untreated erythrocytes did not bind chloroquine with high affinity. At a chloroquine concentration in the medium of 2 microM, for example, menadione-treated erythrocytes bound 70 mumole chloroquine/kg and untreated erythrocytes bound 13.4 mumole/kg. The intracellular location of FP released by menadione was verified by finding that Tween 80 did not prevent chloroquine binding. By contrast, Tween 80 inhibited the binding of chloroquine to erythrocytes treated with extracellular FP. The hemolytic response to menadione was characteristic of the hemolytic response to FP. Thus, 5 microM chloroquine caused hemolysis to increase to 60% from baseline values of 5% in experiments using erythrocytes treated either with 0.5 mM menadione or with 5 microM FP; and, in both cases, the potentiating effect of chloroquine was inhibited by 1 microM mefloquine or 10 microM quinine. Higher concentrations of menadione caused hemolysis in the absence of chloroquine. We conclude that FP released by menadione exists intracellularly in a form that is accessible to bind chloroquine and to express its lytic activity.

Topics: Anemia, Hemolytic; Animals; Erythrocytes; Female; Heme; Hemin; Hemolysis; Humans; Kinetics; Male; Mice; Rats; Receptors, Drug; Vitamin K

The superoxide dismutase inhibitor diethyldithiocarbamate (DDC) was utilized to study the toxic effect of 1,4-naphthoquinone 2-sulfonate (NQ), a structural analog of the hemolytic drug, menadione, on red cells. NQ was shown to react with hemoglobin and result in the generation of superoxide anion (O2-). Red cells treated with NQ were found to undergo a gradual disappearance of their oxyhemoglobin and also hemolyze. Red cells pretreated with DDC to inhibit cellular superoxide dismutase were found to be markedly sensitive to oxyhemoglobin destruction and hemolysis in the presence of NQ. Superoxide dismutase-inhibited red cells were also found to undergo a slow autohemolysis in the absence of NQ. No evidence for lipid peroxidation was obtained for red cells treated with NQ either in the presence or the absence of DDC. Ghosts prepared from superoxide dismutase-inhibited red cells exposed to NQ were found to retain a green hemoglobin-derived pigment.

Topics: Binding Sites; Cytochrome c Group; Ditiocarb; Erythrocytes; Hemolysis; Humans; Kinetics; Naphthoquinones; Oxygen; Oxyhemoglobins; Protein Binding; Spectrophotometry; Superoxide Dismutase; Superoxides; Thiocarbamates; Vitamin K

57 patients with Björk aortic valves had an in-depth study of their coagulation carried out. It seems that the well-anticoagulated group (39 patients) had more marked haemolysis, had a higher mean level of fibrinogen and PDF, but less biological signs of activation of fibrinolysis than the group who were non- or mildly-anticoagulated (18 patients). The increased platelet aggregation, which is often noted, was correlated with the signs of haemolysis, or of activation of the breakdown of fibrinogen. Apart from the problem of haemolysis, anticoagulant treatment appears biologically to be a moderating factor in the activation of the breakdown of fibrinogen and, by this means, of the utilisation of clotting factors.

Topics: Anticoagulants; Aortic Valve; Blood Platelets; Fibrinogen; Heart Valve Prosthesis; Hemolysis; Platelet Aggregation; Vitamin K

Topics: Anaerobiosis; Animals; Bacteroides; Bacteroides Infections; Culture Media; Erythrocytes; Hemin; Hemolysis; Humans; Sheep; Succinates; Vitamin K; Vitamin K 1

Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents; Arthritis; Chlorobenzenes; Chloroquine; Cortisone; Escherichia coli; Estradiol; Germ-Free Life; Hemolysis; In Vitro Techniques; Leukocytes; Lysosomes; Male; Membranes; Paramethasone; Prednisolone; Progesterone; Rabbits; Rats; Surface-Active Agents; Testosterone; Thiazoles; Time Factors; Vitamin K

Topics: Adenosine Triphosphate; Animals; Child, Preschool; Erythrocytes; Glucose; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Kinetics; Phospholipases; Snakes; Venoms; Vitamin K

Topics: Adult; Animals; Cell Membrane Permeability; Erythrocytes; Hemolysis; Humans; Hydrogen Peroxide; Infant; Rats; Vitamin E; Vitamin E Deficiency; Vitamin K

Topics: Cell Membrane; Erythrocytes; Hemoglobins; Hemolysis; Humans; In Vitro Techniques; Oxidation-Reduction; Peroxidases; Sodium; Vitamin K

Topics: Adolescent; Adult; Anticoagulants; Blood Coagulation Tests; Child; Female; Heart Valve Diseases; Heart Valve Prosthesis; Hemodynamics; Hemolysis; Heparin; Humans; Male; Middle Aged; Mitral Valve; Postoperative Complications; Sepsis; Thromboembolism; Vitamin K

Topics: Aniline Compounds; Ascorbic Acid; Azides; Blood Glucose; Catalase; Chlorates; Erythrocytes; Glucosephosphate Dehydrogenase; Glutathione; Heinz Bodies; Hemoglobinometry; Hemolysis; Humans; Methemoglobin; Nitrites; Osmotic Fragility; Peroxidases; Phenylhydrazines; Potassium; Primaquine; Sodium; Vitamin K

Topics: Chromium Isotopes; Drug Hypersensitivity; Erythrocytes; Favism; Female; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Heterozygote; Humans; Immunogenetics; Mosaicism; Primaquine; Sex Chromosomes; Vitamin K

Topics: Animals; Cell Membrane; Cell Membrane Permeability; Chloromercuribenzoates; Erythrocytes; Ethers; Glutathione; Hemoglobins; Hemolysis; In Vitro Techniques; Lipid Metabolism; Male; Microscopy, Electron; Osmotic Fragility; Phosphates; Potassium; Rats; Sucrose; Sulfhydryl Compounds; Vitamin K

Topics: Animals; Diet Therapy; Erythrocytes; Hemolysis; Male; Rats; Vitamin E; Vitamin E Deficiency; Vitamin K

Topics: Adult; Erythrocyte Aging; Glutathione Reductase; Heinz Bodies; Hemolysis; Humans; Infant, Newborn; Infant, Newborn, Diseases; Methylene Blue; Primaquine; Vitamin K

Topics: Adult; Erythrocytes; Glycolysis; Hemolysis; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lactates; Methylene Blue; Potassium; Vitamin K

Topics: Hemoglobins; Hemolysis; Humans; Infant, Newborn; Infant, Newborn, Diseases; Methemoglobin; Methylene Blue; Nitrites; Vitamin K

Topics: Aniline Compounds; Animals; Antimalarials; Catalase; Enzyme Inhibitors; Erythrocytes; Glucosephosphate Dehydrogenase Deficiency; Glucosephosphates; Hemolysis; Hemolytic Agents; Herbicides; Hydrogen Peroxide; Mice; Pharmacology; Phenylhydrazines; Primaquine; Research; Toxicology; Vitamin K

Topics: Antimalarials; Catalase; Chloroquine; Erythrocytes; Ethanol; Glucosephosphate Dehydrogenase Deficiency; Glucosephosphates; Hemolysis; Hemolytic Agents; Hydrogen Peroxide; Hydroquinones; Pharmacology; Phenols; Phenylhydrazines; Primaquine; Research; Triazoles; Vitamin K

Topics: Aldehydes; Cell Membrane; Cell Membrane Permeability; Electrons; Ergocalciferols; Glycosides; Hemolysis; Hydroquinones; Microscopy; Microscopy, Electron; Oxidation-Reduction; Rabbits; Research; Squalene; Ubiquinone; Vitamin A; Vitamin K; Vitamin K 1; Vitamins

Topics: Animals; Bilirubin; Hemoglobins; Hemolysis; Hyperbilirubinemia; Jaundice; Rats; Vitamin K

Topics: Acetaminophen; Acetanilides; Analgesics; Analgesics, Non-Narcotic; Antipyretics; Bilirubin; Erythrocytes; Glucosephosphate Dehydrogenase; Glucuronates; Glutathione; Hemolysis; Humans; Hyperbilirubinemia; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Pharmacology; Toxicology; Vitamin K

Topics: Administration, Intravenous; Antifibrinolytic Agents; Hemolysis; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Prothrombin; Vitamin K; Vitamin K 1

Topics: Animals; Cell Death; Hemoglobinuria; Hemolysis; Naphthoquinones; Rats; Vitamin E Deficiency; Vitamin K; Vitamins

Topics: Animals; Antifibrinolytic Agents; Hemolysis; Lagomorpha; Rabbits; Retinoids; Vitamin K