Methylene blue metabolism

Toxicity can be overcome by giving methylene blue, a dye that is metabolized to a form that reduces the Fe of methemogiobin back to the Fe state. 

At the physiological level it is well established that vital dyes such as nile blue, neutral red and methylene blue retard larval development under normal lighting conditions (12L/12D with source unspecified) (25 27). Female but not male pupal weights are also reduced. Unfortunately experiments were conducted without dark controls so that it is difficult to evaluate the role of photosensitization in these effects. As house flies and fire ants succumb to photosensitization, they lose motor control and become more excitable (28). This suggested a neurotoxic effect and investigation of fire ant acetylcholinesterase vitro revealed that this enzyme was sensitive to photo-oxidation. vivo results, however, revealed no effect on the enzyme which suggests another mode of action. Epoxldatlon of cholesterol and membrane lysis may be alternative primary sites. If this were the case ecdysone metabolism of insects would probably also be effected. 

Residues of methylene blue in edible animal tissues are of public health concern because tliis dye and its metabolites are mutagenic (74). Metabolism studies in cattle have indicated that methylene blue can be eliminated in urine partly unchanged, partly metabolized to leucomethylene blue, or demethylated to N-methyl homologues of thionin, the completely demethylated metabolite of methylene blue, or reduced in vivo and subsequently eliminated in its leuco-form or in one or more chromogenic substances (75). 

Ray et al. [77] used an indirect method based on AAS for the determination of sulfide in flooded acid sulfate soils. Hydrogen sulfide, evolved during the anaerobic metabolism of sulfate, is readily converted into insoluble metal sulfides, chiefly iron sulfide, in flooded acid sulfate soils. A method for determining sulfide is based on the precipitation of the sulfide as zinc sulfide and subsequent determination by methylene blue formation or iodine titrimetry. 

The toxic action of bilirubin on tissue metabolism has been demonstrated both by in vitro and in vivo experiments. Lathe (LI) added bilirubin to brain brei, in concentrations such as occur in hemolytic disease of the newborn and prematurity, and observed a decrease in oxygen consumption. Day (D3) was able to reverse this depressed respiration by the addition of cytochrome c or methylene blue. Bowen and Waters (B16) then showed that this reversal could also be efFected by diphosphopyridine nucleotide. Zetterstrom and Ernster (Zl), using isolated rat liver mitochondria, showed that bilirubin in concentrations... 

Barron ESG, Harrop GA. Studies on blood cell metabolism II. The effect of methylene blue and other dyes upon the glycolysis and lactic acid formation of mammalian and avian erythrocytes. J. Biol. Chem. 1928 79 65-87. 

Animals may manifest toxicity to salicylates with signs and symptoms similar to those seen in humans. These may include fever, hyperpnea, seizures, respiratory alkalosis, metabolic acidosis, gastric hemorrhage, and kidney damage. Methemoglobinemia has also been seen in animals following salicylate toxicity. Activated charcoal has been used in animals. Methylene blue or ascorbic acid may be utilized for the treatment of methemoglobinemia. 

When tested under identical conditions, some synthetic antioxidants are more potent than tocopherol. For example, the approximate EDso for amylhydroquinone is 0.5, for methylene blue 0.3, and for DPPD (N,N -diphenyl-p-phenylenediamine) 0.03 ixg (Schwarz and Lee, 1961). We have postulated since 1956 that tocopherol may be converted into an active form before exerting its catalytic metabolic effect (Rodnan et al., 1956). In this regard it is noteworthy that a synthetic preparation of an a-tocoph-... 

The role of the old yellow enzyme in metabolism is not known. It is reduced by TPNH2 or DPNH2 and the reduced form is reoxidized by atmospheric oxygen. Its activity in this system, however, is too low to account for more than a fraction of yeast respiration. It is more rapidly reoxidized by methylene blue, but very slowly, if at all, by cytochrome c. 

Absorption, metabolism, and excretion. Urinaiy exoelion is the main route of elimination, and die drog colors the urine blue or green as the oxidation product (methylene blue sulfone) is formed. 

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