The Effect of Methylene Blue and Its Metabolite—Azure I—on Bioenergetic Parameters of Intact Mouse Brain Mitochondria

IF 0.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Pub Date : 2022-05-17 DOI:10.1134/S1990750822020044

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

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Abstract—

Methylene blue, a phenothiazine dye, that is widely used in medicine and is under clinical trials as an agent for 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 mitochondria and transfer 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 yet. We have shown that in contrast to methylene blue, azure I 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, 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. Thus, 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 agent, but does not question its antidepressant effects.

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亚甲基蓝及其代谢物蔚蓝i对完整小鼠脑线粒体生物能量参数的影响

亚甲基蓝是一种吩噻嗪类染料，广泛应用于医学，目前正在临床试验中作为治疗阿尔茨海默病的药物。亚甲基蓝独特的治疗效果的因素之一是它的氧化还原特性，允许实现替代电子传输:染料接受线粒体中还原等量物的电子，并将其转移到呼吸链或分子氧的其他组成部分。亚甲基蓝的n -二甲基化代谢物Azure I可能是一种比亚甲基蓝更有效的化合物，但其替代电子传递的能力尚未得到研究。我们已经证明，与亚甲基蓝相比，天青I无法恢复分离小鼠脑线粒体的膜电位，受到鱼藤酮的抑制，因此无法进行呼吸链复合体I的旁路。此外，与亚甲基蓝相比，天青I的加入不会影响线粒体呼吸速率，而亚甲基蓝则会增加非磷酸化呼吸速率。同时，两种染料都刺激H2O2的产生。因此，只有亚甲基蓝能够替代电子传递，而天蓝I不产生络合物I旁路。这限制了其仅作为线粒体靶向药物的治疗应用，但不质疑其抗抑郁作用。

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来源期刊

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

1.10

自引率

0.00%

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期刊介绍： Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry covers all major aspects of biomedical chemistry and related areas, including proteomics and molecular biology of (patho)physiological processes, biochemistry, neurochemistry, immunochemistry and clinical chemistry, bioinformatics, gene therapy, drug design and delivery, biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine. The journal also publishes review articles. All issues of the journal usually contain solicited reviews.