Methylene blue elicits non-genotoxic H

DNA damage Methylene blue Neuroprotection Rotenone Toxicity mtDNA

Journal

Journal of applied biomedicine
ISSN: 1214-0287
Titre abrégé: J Appl Biomed
Pays: Poland
ID NLM: 101221755

Informations de publication

Date de publication:
Jun 2019
Historique:
received: 10 01 2018
accepted: 14 05 2019
entrez: 15 12 2021
pubmed: 1 6 2019
medline: 1 6 2019
Statut: ppublish

Résumé

Methylene blue (MB) is a promising compound with a broad range of neuroprotective activity. One of therapeutic effects is the activation of mitochondrial biogenesis via Nrf2/ARE signaling cascade. Probably, mild oxidative stress caused by MB-depended H2O2 production is a trigger for activation of this signaling cascade. So mechanistically, MB can be regarded as prooxidant. We investigated the dose-dependent H2O2 production in intact brain mitochondria and showed the increase in the H2O2 production after adding as little as 50 nM MB. We have not found genotoxic effect of therapeutic concentration of MB to mitochondrial genome. 100 μM MB selectively damaged fragments of mitochondrial DNA, which correlated with the number of purine-T-G-purine (RTGR)-sequences in studied fragments. Furthermore, 20 μM MB combined with the red light caused the formation of singlet oxygen, which strongly damaged mitochondrial DNA in all studied fragments. We did not observe mitochondrial DNA lesions in brain after single intraperitoneal injection of MB in the concentration of 50 mg/kg. Furthermore, we showed the neuroprotective properties of MB pretreatments after rotenone injection. Therefore, we suggest that MB-induced mild oxidative stress does not have genotoxic effect on mitochondrial DNA.

Identifiants

pubmed: 34907732
doi: 10.32725/jab.2019.008
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

107-114

Subventions

Organisme : President of the Russian Federation
ID : MK3173.2019.11
Pays : Russian Federation
Organisme : Ministry of Education and Science of the Russian Federation
ID : 6.4656.2017/8.9
Pays : Russian Federation
Organisme : Ministry of Education and Science of the Russian Federation
ID : 4656.2017/8.9
Pays : Russian Federation
Organisme : Russian Fund for Basic Research
ID : 19-44-360011
Pays : Russian Federation

Déclaration de conflit d'intérêts

The authors confirm that the study causes no conflict of interests as related to funding, commercial activity, intellectual property rights, or other conceivable issues.

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Auteurs

Artem P Gureev (AP)

Voronezh State University, Faculty of Medicine and Biology, Department of Genetics, Cytology and Bioengineering, Voronezh, Russia.

Ekaterina A Shaforostova (EA)

Voronezh State University, Faculty of Medicine and Biology, Department of Genetics, Cytology and Bioengineering, Voronezh, Russia.

Denis A Laver (DA)

Voronezh State University, Faculty of Medicine and Biology, Department of Genetics, Cytology and Bioengineering, Voronezh, Russia.

Victoria G Khorolskaya (VG)

Voronezh State University, Faculty of Medicine and Biology, Department of Genetics, Cytology and Bioengineering, Voronezh, Russia.

Mikhail Yu Syromyatnikov (MY)

Voronezh State University, Faculty of Medicine and Biology, Department of Genetics, Cytology and Bioengineering, Voronezh, Russia.

Vasily N Popov (VN)

Voronezh State University, Faculty of Medicine and Biology, Department of Genetics, Cytology and Bioengineering, Voronezh, Russia.
Voronezh State University of Engineering Technologies, Voronezh, Russia.

Classifications MeSH