Studies of the efficacy and potential hazards of methylene blue therapy in aniline‐induced methaemoglobinaemia

British Journal of Haematology - Tập 54 Số 1 - Trang 29-41 - 1983
John W. Harvey1, Alan S. Keitt1
1Department of Physiological Sciences, College of Veterinary Medicine, and Departments of Pathology and Medicine, College of Medicine, J. Hillis Miller Health Center, University of Florida, Gainesville, Florida

Tóm tắt

Summary. The similarity between poison and antidote was known to the ancient Greeks who used the same word, pharmakon, for both. This paper presents evidence that aniline (the toxin) and methylene blue (the therapy) are in fact remarkably similar and additive in some of their effects on erythrocytes. Studies were prompted by a case of aniline‐induced methaemoglobinaemia in which two injections of methylene blue did not rapidly eliminate cyanosis and were followed by severe, delayed haemolysis. Interactions between aniline and methylene blue were studied in cats which, although showing important differences from man in their haemoglobin and splenic vasculature, represent a useful model. Methylene blue potentiated the oxidative denaturation of haemoglobin by aniline as judged by the size and number of Heinz bodies and their turbidity in haemolysate. It also aggravated and prolonged the fall in erythrocyte reduced glutathione content which occurred at a time of maximum Heinz body production. While methylene blue in judicious dosage will reduce the content of methaemoglobin after aniline exposure, it may not eliminate visible cyanosis. Repeated injections of methylene blue can markedly aggravate subsequent haemolysis without further lowering methaemoglobin content.

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Tài liệu tham khảo

Beutler E., 1975, Red Cell Metabolism. A Manual of Biochemical Methods, 114

10.1002/aja.1001610203

Brewer G.J., 1961, Studies on the mechanism of primaquine‐type hemolysis: the effect of methylene blue. (Abstract), Clinical Research Proceedings, 9, 65

10.3109/03630267709003909

10.1111/j.1365-2141.1975.tb00540.x

10.1111/j.1365-2141.1964.tb00715.x

10.1097/00005792-195505000-00001

10.1042/bj1730019

Gabuzda T.G., 1967, Oxidative precipitation of hemoglobin H and its relation to reduced glutathione, Journal of Laboratory and Clinical Investigation, 70, 581

10.1097/00000441-197405000-00005

10.1016/S0022-3476(61)80064-4

10.1001/jama.1945.02860330023006

Hamilton M.N., 1974, Cat hemoglobin pH dependency of cooperativity and ligand binding, Journal of Biological Chemistry, 249, 1323

Hänel A., 1964, Über die toxischen Wirkungen von Methylene Blue auf Erythrocyten in Vivo, Acta Biologica et Medica Germanica, 12, 644

10.1111/j.1365-2044.1977.tb11608.x

10.1111/j.1365-2141.1976.tb00922.x

Harvey J.W., 1979, Benzocaine‐induced methemoglobinemia in dogs, Journal of the American Veterinary Medical Association, 175, 1171

Herzog P., 1978, Methemoglobinemia in the newborn infant, Clinics in Haematology, 7, 75, 10.1016/S0308-2261(21)00571-3

Jain N.C., 1973, Studies on the occurrence and persistence of Heinz bodies in erythrocytes of the cat, Folia Haematologica, 99, 28

Kearney T.E., 1982, Aniline induced methemoglobinemia. (Abstract), Veterinary and Human Toxicology, 24, 287

Kiese M., 1966, The biochemical production of ferrihemoglobin forming derivatives from aromatic amines, and mechanisms of ferrihemoglobin formation, Pharmacological Reviews, 18, 1091

10.1007/BF00506490

10.1016/0006-2952(72)90288-2

10.1139/o77-086

Layne W.R., 1969, Methylene blue uptake and reversal of chemically induced methemoglobinemias in human erythrocytes, Journal of Pharmacology and Experimental Therapeutics, 165, 36

10.1001/archinte.1964.03860100112013

10.1172/JCI108531

Prins H.K., 1969, Biochemical Methods in Red Cell Genetics, 115

10.7326/0003-4819-75-1-83

10.1016/0009-8981(69)90143-0

Schalm O.W., 1975, Veterinary Hematology, 36

Smith R.P., 1972, Hemoglobin, methylene blue and oxygen interactions in human red cells, Journal of Pharmacology and Experimental Therapeutics, 183, 549

10.1042/bj0840360

10.1016/0006-2952(66)90305-4

Wintrobe M.M., 1974, Clinical Hematology, 1013