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

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 (ther 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.