naphthoquinones and Glucosephosphate-Dehydrogenase-Deficiency

Over a 10-year period, 15 glucose-6-phosphate dehydrogenase (G6PD)-deficient male newborns were admitted to Al-Jahra Hospital with acute haemolysis a few days after applying henna dye over the body, which is a unique Bedouin tribal practice to celebrate the arrival of the first-born boy. Laboratory investigations revealed significant anaemia, reticulocytosis and indirect hyperbilirubinaemia among the index newborns as compared with controls (p < 0.001). The mean (SD) haemoglobin concentration in index patients was 113.4 (13.4) g/l vs 171.2 (11.2) g/l in controls, reticulocytic count 13.8% (4.2%) vs 1.4% (0.74%), and indirect bilirubin 382.8 (58.7) mumol/l vs 63.7 (61.4) mumol/l. G6PD-deficient newborns with haemolysis linked to henna application had delayed age at presentation and a higher reticulocytic count and hyperbilirubinaemia compared with non-henna-induced haemolysis (p < 0.05). Percutaneous henna absorption is well recognized and clinical findings support the harmful effect of henna on G6PD-deficient red blood cells. A local health education programme has been established to prevent the use of henna dye in infancy.

Topics: Administration, Topical; Antifungal Agents; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Infant, Newborn; Male; Medicine, Ayurvedic; Naphthoquinones; Skin Absorption

Topics: Child; Drug Hypersensitivity; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Male; Naphthoquinones; Treatment Outcome

Topics: Bilirubin; Blood Transfusion; Coloring Agents; Glucosephosphate Dehydrogenase Deficiency; Humans; Hyperbilirubinemia; Infant, Newborn; Male; Naphthoquinones; Phototherapy; Treatment Outcome

Henna is a traditional cosmetic agent and is used worldwide. It is used worldwide not only as a cosmetic agent to stain the hair, skin and nails but also is applied to the body on lesions in the treatment of seborrheic dermatitis or fungal infections. Different pathologies have been described as caused by henna. The aim of this study is to draw attention to the adverse effects of henna, applied over the whole body, observed in glucose-6-phosphate dehydrogenase (G6PD) enzyme deficient siblings. In the present paper, we report on two siblings with G6PD deficiency who developed haemolytic anaemia following topical application of henna to their whole body to treat skin lesions. Their parents were also found to be G6PD deficient. Even though anti-inflammatory, analgesic and antipyretic effects of henna have been shown, it may cause severe side-effects in some cases. For this reason, especially, in the regions where G6PD enzyme deficiency is common, people should be informed about the side-effects of topical henna application and clinicians should be aware of these manifestations.

Topics: Administration, Topical; Anemia, Hemolytic; Child; Dermatologic Agents; Female; Glucosephosphate Dehydrogenase Deficiency; Humans; Ichthyosis Vulgaris; Male; Naphthoquinones; Pedigree; Siblings

Lawsone (2-hydroxy-1,4-naphthoquinone) is the active ingredient of henna (Lawsonia alba), the crushed leaves of which are used as a cosmetic dye. Application of henna can induce a severe hemolytic anemia, and lawsone is thought to be the causative agent. Administration of lawsone to rats has been shown to induce a hemolytic response that is associated with oxidative damage to erythrocytes. However, direct exposure of isolated erythrocytes to lawsone did not provoke oxidative damage, suggesting that lawsone must undergo extra-erythrocytic bioactivation in vivo. In the present study, the survival of rat 51Cr-labeled erythrocytes in vivo after in vitro exposure to lawsone and its hydroquinone form, 1,2,4-trihydroxynaphthalene (THN) has been examined. Neither lawsone nor THN were directly hemolytic or methemoglobinemic, even at high concentrations (>3 mM). Lawsone had no effect on erythrocytic GSH levels, whereas THN (3 mM) induced a modest depletion (approximately 30%). Cyclic voltammetry revealed that the lack of hemotoxicity of lawsone was associated with a poor capacity to undergo redox cycling. In contrast, ortho-substituted 1,4-naphthoquinones without a 2-hydroxy group, such as 2-methyl- and 2-methoxy-1,4-naphthoquinone, were redox active, were able to deplete GSH, and were direct-acting hemolytic agents. An oxidant stress-associated hemolytic response to lawsone could be provoked, however, if it was incubated with GSH-depleted erythrocytes. The data suggest that lawsone is a weak direct-acting hemolytic agent that does not require extra-erythrocytic metabolism to cause hemotoxicity. Thus, the hemolytic response to henna may be restricted to individuals with compromised antioxidant defenses.

Topics: Anemia, Hemolytic; Animals; Cell Survival; Chromium Radioisotopes; Coloring Agents; Cytoskeletal Proteins; Electrochemistry; Glucosephosphate Dehydrogenase Deficiency; Glutathione; Hemolysis; Magnetic Resonance Spectroscopy; Male; Methemoglobin; Naphthoquinones; Oxidation-Reduction; Oxidative Stress; Pentose Phosphate Pathway; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

To evaluate the in vitro oxidation potential of lawsone (2-hydroxy-1,4 naphthoquinone). Lawsone is a chemical present in henna, the crushed leaves of which are used worldwide as a cosmetic agent to stain the hair, skin, and nails.. Venous blood from glucose-6-phosphate dehydrogenase (G6PD)-normal and G6PD A- subjects were incubated with various amounts of lawsone for 2 hours at 37 degrees C. Reduced glutathione and methemoglobin (MHb) levels were measured before and after incubation.. Final molar concentrations of lawsone in normal blood of 1.4, 2.8, 5.7, and 8.6 x 10-3 mol/L increased MHb percentages from 0.5% to 2.2%, 8.3%, 9.5% and 12.5%, respectively. In a C6PD A- blood, MHb percentages were 19.8%, 32.2%, 44.9%, and 53.9%. At a lawsone concentration of 2.8 x 10-3 mol/L, blood from 15 healthy adults formed MHb percentages of 7.4% +/- 3.3% (+/- 1 SD); in blood from 4 G6PD A- adults, percentages were 44.5%, 40.6%, 41.3%, and 42.8%. Simultaneous measurements of reduced glutathione revealed preincubation values of greater than 40 mg/100 mL of red cells in blood of healthy and G6PD A- subjects. Postincubation values were greater than 40 in blood of healthy subjects and less than 40 in blood of G6PD A- subjects.. These in vitro observations indicate that lawsone is an agent capable of causing oxidative hemolysis. In regions of the world where there is a high incidence of G6PD deficiency and unexplained hyperbilirubinemia, oxidative hemolysis secondary to the cutaneous application of henna could be the initiating event.

Topics: Adult; Coloring Agents; Cosmetics; Erythrocytes; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Glutathione; Hemolysis; Humans; Infant, Newborn; Jaundice, Neonatal; Methemoglobin; Naphthoquinones; Oxidation-Reduction

Topics: Antifibrinolytic Agents; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Humans; Infant, Newborn; Jaundice; Jaundice, Neonatal; Naphthoquinones; Nigeria; Vitamin K

Topics: Catalase; Erythrocytes; Glucose; Glucosephosphate Dehydrogenase Deficiency; Glucosephosphates; Glutathione; Hemoglobins; Humans; Methemoglobin; NAD; NADP; Naphthoquinones