Journal
JOURNAL OF APPLIED BIOMEDICINE
Volume 17, Issue 2, Pages 107-114Publisher
UNIV SOUTH BOHEMIA
DOI: 10.32725/jab.2019.008
Keywords
DNA damage; Methylene blue; mtDNA; Neuroprotection; Rotenone; Toxicity
Funding
- Russian Federation [MK-3173.2019.11]
- Ministry of Education and Science of the Russian Federation [N 6.4656.2017/8.9]
- Russian Fund for Basic Research [19-44-360011 r_a]
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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 mitochondrialgenome. 100 mu M MB selectively damaged fragments of mitochondrial DNA, which correlated with the number of purine-T-G-purine (RTGR)-sequences in studied fragments. Furthermore, 20 mu M 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.
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