Spectroscopic Measurement of Methylene Blue Distribution in Organs and Tissues of Hamadryas Baboons during Oral Administration

Elizaveta I Kozlikina,Evgeniya I Muhametzyanova,Anastasia V Ryabova,Gleb A Zhemerikin,Artem A Shiryaev,Igor V Reshetov,Dmitry V Bulgin,Dzina D Karal-Ogly,Kanamat T Efendiev,Daria V Pominova,Victor B Loschenov,Natalia S Rudenko,Aleksei S Skobeltsin,Olga G Kulik

doi:10.3390/photonics8080294

Abstract

New research on Methylene Blue (MB), carried out in 2020, shows that it can be an effective antiviral drug as part of COVID-19 treatment. According to the research findings, MB has potential as a direct antiviral drug for the prevention and treatment of COVID-19 in the first stages of the disease. However, the MB accumulation by various types of tissues, as well as by immune cells, has not been previously studied. Therefore, the objective of this study was to obtain spectral data on the interstitial distribution of the administered drug in endothelial tissues in primates. The data on interstitial MB distribution obtained by spectroscopic measurement at both macro- and microlevels during oral administration to Hamadryas baboon individuals demonstrate that MB accumulates in mucous membranes of gastrointestinal tract and the tissues of the respiratory, cardiovascular, immune, and nervous systems. Additionally, it was found that MB was present in lung and brain myeloid cells in significant concentrations, which makes it potentially useful for protection from autoimmune response (cytokine storm) and as a tool for the correction of immunocompetent cells’ functional state during laser irradiation. Since the cytokine storm starts from monocytic cells during SARS-CoV-2 cellular damage and since tumor-associated macrophages can significantly alter tumor metabolism, accumulation of MB in these cells provides a reason to conclude that the immune response correction in COVID-19 patients and change in macrophages phenotype can be achieved by deactivation of inflammatory macrophages in tissues with MB using laser radiation of red spectral range.

Highlights

Methylene Blue (MB) is a thiazine dye that is extensively used in various fields of science
The MB fluorescence spectra in the organs of primates 3 and 24 h after oral administration were registered and the corresponding fluorescence indices for each organ were calculated (Formula (1) was used taking into account the subtraction of endogenous fluorescence obtained from the control Primate C)
In the results presented above, the organs of two primates were examined after oral administration of MB after 3 and 24 h, respectively, by using both a laser scanning confocal microscope to assess the accumulation of the drug in the thin layer of the sample and a fiber-optic spectrometer to evaluate the average accumulation of the drug over the entire depth of the investigated organ, into which the laser light penetrates

Summary

Introduction

MB is a thiazine dye that is extensively used in various fields of science. MB is a well-known low-toxic biocompatible material. MB solutions are injected intravenously for cyanide, carbon monoxide, and hydrogen sulfide poisonings [7,8]. MB had been used in psychiatry as well [9] It was administered in doses from 15 to 300 mg daily, and the maximum concentration of MB in the blood was registered within 1 to 2 h after administration. It was not shown what the effective dose and blood concentration for psychiatric indications should be. Patients who used serotonin re-uptake inhibitors experienced serotonin toxicity after MB intravenous injection [10]

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