Effect of methylene blue and its metabolite — azure I — on bioenergetic parameters of intact mice brain mitochondria

Gureev A.P.1 , Samoylova N.A.2, Potanina D.V.2, Popov V.N.1

1. Voronezh State University, Voronezh, Russia; Voronezh State University of Engineering Technologies, Voronezh, Russia
2. Voronezh State University, Voronezh, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20216706485      PubMed Id: 34964442
Year: 2021  Volume: 67  Issue: 6  Pages: 485-490
Methylene blue is a phenothiazine dye that is widely used in medicine and clinical trials for the treatment of Alzheimer's disease. One of the factors of the unique therapeutic effect of methylene blue is its redox properties, allowing implementation of alternative electron transport — the dye accepts electrons from reducing equivalents in the mitochondria and transfer it them to other components of the respiratory chain or molecular oxygen. Azure I, an N-dimethylated metabolite of methylene blue, is potentially a more effective compound than methylene blue, but its ability for alternative electron transport has not been studied. We have shown that azure I, unlike methylene blue, is unable to restore the membrane potential in isolated mouse brain mitochondria, inhibited by rotenone and, therefore, is unable to perform bypass of the respiratory chain Complex I. Moreover, the addition of azure I does not affect the rate of mitochondrial respiration in contrast to methylene blue, which increases the rate of non-phosphorylation respiration. At the same time, both dyes stimulate an increase in H2O2 production. As a consequence, only methylene blue is capable of alternative electron transport, while azure I does not produce complex I bypass. This limits its therapeutic application only as a mitochondrial-targeted drug, but not as a substance with a potentially powerful antidepressant effect.
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Keywords: methylene blue, azure I, mitochondria, alternative electron transport

Gureev, A. P., Samoylova, N. A., Potanina, D. V., Popov, V. N. (2021). Effect of methylene blue and its metabolite — azure I — on bioenergetic parameters of intact mice brain mitochondria. Biomeditsinskaya Khimiya, 67(6), 485-490.
This paper is also available as the English translation: 10.1134/S1990750822020044
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