salicylates and Glucosephosphate-Dehydrogenase-Deficiency

Salicylic acid and its derivatives are extensively used medications for the treatment of systemic and local diseases. However, injudicious use of aspirin as well as other derivatives of salicylic acid, may cause systemic and oral complications such as mucosal burns and oral ulcers. In children, topical administration of these drugs, even in small dosages, may cause adverse reactions. This report shows a case of an 8 year old boy with G6PD deficiency, who had a mucosal burn caused by application of a cholinsalicylate paste. Three days later, the child developed oral ulcers, malaise and fever. The present case is characteristic of the enigmatic nature of the etiology and diagnosis of oral lesions, and the possible connection between cholinsalicylate systemic absorption and hemolytic anemia is discussed.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Burns, Chemical; Child; Choline; Dental Care for Chronically Ill; Drug Combinations; Glucosephosphate Dehydrogenase Deficiency; Humans; Male; Mouth Mucosa; Oral Ulcer; Salicylates

It has been hypothesized that enhanced oxidant sensitivity of glucose-6-phosphate dehydrogenase (G6PD) deficient red cells(RBCs) is the underlying mechanism for drug- or chemical-induced hemolytic crises in G6PD-deficiency. To further test this hypothesis, we used an alloxan-glutathione system to mimic oxidative stress and see how oxidative damage might affect RBC deformability. RBC deformability, a major determinant of RBC survival in vivo, was monitored by a laser viscodiffractometer. Under our experimental conditions, GSH alone had very little effect on the deformability of either normal or G6PD-deficient RBCs. In contrast, alloxan alone induced a small but significant decrease in the deformability of either normal or G6PD-deficient RBCs. Interestingly, alloxan and GSH together induced a further decrease in the deformability of either normal or G6PD-deficient RBCs. The decrease in deformability in G6PD-deficient RBCs was much more profound than in normal RBCs. In addition, an alloxan-vitamin C system produced a similar deleterious effect on RBC deformability as that produced by the alloxan-GSH system. Appreciable amount of hydroxyl radicals was generated by both alloxan-GSH and alloxan-vitamin C systems as evidenced by the production of hydroxylated products of salicylate which was used as a radical trap. Moreover, salicylate could ameliorate the deleterious effect of the alloxan system on the deformability of RBCs. Taken together, our results demonstrated that G6PD-deficient RBCs were particularly susceptible to oxidant-induced damage leading to a dramatic decrease in their deformability and thus provided strong support for the hypothesis that enhanced oxidant sensitivity of G6PD-deficient RBCs is the underlying mechanism for accelerated destruction of these RBCs in vivo.

Topics: Alloxan; Ascorbic Acid; Erythrocyte Deformability; Erythrocytes; Glucosephosphate Dehydrogenase Deficiency; Glutathione; Humans; Hydroxyl Radical; Hydroxylation; Salicylates; Salicylic Acid

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Drug Therapy, Combination; Drug Tolerance; Female; Glucosephosphate Dehydrogenase Deficiency; Humans; Imidazoles; Infant; Male; Salicylates; Time Factors

Salicylate is known to uncouple mitochondrial oxidative phosphorylation. Since the viability of pyruvate-kinase-deficient reticulocytes depends on ATP generated by mitochondrial metabolism, this study examined the effects of salicylate on erythrocytes deficient in pyruvate kinase. When deficient erythrocytes from patients with severe hemolysis were incubated with salicylate (2 to 30 mg per deciliter), there was a marked decrease (25 to 75 percent) in ATP. In addition, this drug-induced ATP depletion produced cell potassium and water loss, and the normal oxidant responsiveness of the hexose-monophosphate shunt was blunted. Since these cellular abnormalities are associated with accelerated hemolysis in vivo, the data suggest that aspirin therapy may aggravate hemolysis in patients with pyruvate kinase deficiency whose erythrocyte manifest sensitivity to salicylate in vitro.

Topics: Adenosine Triphosphate; Anemia, Hemolytic; Aspirin; Erythrocytes; Glucose; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Hexoses; Humans; Mitochondria; Oxidative Phosphorylation; Pyruvate Kinase; Salicylates

Topics: Erythrocytes; Glucosephosphate Dehydrogenase Deficiency; Humans; Mutation; Salicylates

Topics: Adult; Anemia, Hemolytic; Blood Cell Count; Blood Group Antigens; Blood Transfusion; Child; Child, Preschool; Female; Glucosephosphate Dehydrogenase Deficiency; Hemoglobinopathies; Hemoglobinuria; Humans; Male; Prednisolone; Salicylates; Sri Lanka; Thalassemia

Topics: Anemia; Anemia, Hemolytic; Barbiturates; Catalase; Cholinesterases; Genetics, Medical; Glucosephosphate Dehydrogenase Deficiency; Glucosephosphates; Humans; Hydrogen Peroxide; Isoniazid; Malaria; Pharmacogenetics; Pharmacology; Porphyrias; Primaquine; Salicylates; Succinylcholine; Toxicology

Topics: Analgesics; Analgesics, Non-Narcotic; Anemia; Anemia, Hemolytic; Antimalarials; Antipyretics; Erythroblastosis, Fetal; Female; Fetal Diseases; Glucosephosphate Dehydrogenase Deficiency; Glucosephosphates; Humans; Hyperbilirubinemia; Infant; Infant, Newborn; Infant, Newborn, Diseases; Jaundice; Jaundice, Neonatal; Maternal-Fetal Exchange; North Carolina; Novobiocin; Pregnancy; Salicylates; Sulfisoxazole; Toxicology; Vitamin K