Spectroscopic Study of Methylene Blue Interaction with Coenzymes and its Effect on Tumor Metabolism.

Abstract

The aim of the investigation is to study the interaction of methylene blue (MB) with NADH, FADH₂ coenzymes and lactate, and to evaluate a long-term effect of its intravenous or oral introduction on tumor metabolism in vivo.

Materials and methods: The MB interaction with NADH, FADH₂ coenzymes and lactate was studied using absorption spectrophotometry. A long-term effect of MB on tumor metabolism in vivo was investigated on a mice model of Ehrlich carcinoma. The effect of MB on tumor metabolism in vivo was assessed using time-resolved fluorescence microscopy based on the NADH fluorescence lifetime.

Results: NADH has been established to be the main coenzyme with which MB interacts. The reduction of the lactate quantity is mediated by the shift of tumor metabolism as a result of MB interaction with the NADH. In the experiments in vivo, no noticeable tumor growth rate reduction was observed in the groups with intravenous MB introduction in comparison with the control. In the group receiving MB with drinking water, a decrease of the tumor growth rate, reduction of oxygenation level, and a1/a2 metabolic index were observed, which confirms the shift from glycolysis to oxidative phosphorylation.

Conclusion: The possibility of using MB for the tumor metabolism correction and growth rate reduction has been demonstrated, however, the time of therapy and MB concentration should be optimized to obtain more pronounced therapeutic effect.