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.
- MeSH
- insekticidy škodlivé účinky MeSH
- laboratorní zvířata MeSH
- methylenová modř farmakologie terapeutické užití MeSH
- mitochondriální DNA účinky léků MeSH
- mitochondrie účinky léků MeSH
- modely nemocí na zvířatech MeSH
- mozek metabolismus účinky léků ultrastruktura MeSH
- myši MeSH
- neuroprotektivní látky MeSH
- peroxid vodíku farmakologie metabolismus MeSH
- poškození DNA genetika účinky léků MeSH
- rotenon * škodlivé účinky MeSH
- techniky in vitro MeSH
- Check Tag
- myši MeSH
- Publikační typ
- práce podpořená grantem MeSH
