Do mitochondriotropic antioxidants prevent chlorinative stress-induced mitochondrial and cellular injury?
Reactive chlorine species such as hypochlorous acid (HOCl) are cytotoxic oxidants generated by activated neutrophils at the sites of chronic inflammation. Since mitochondria are key mediators of apoptosis and necrosis, we hypothesized that mitochondriotropic antioxidants could limit HOCl-mediated intracellular oxidative injury to human fetal liver cells, preserve mitochondrial function, and prevent cell death. In this current study, we show that recently developed mitochondria-targeted antioxidants (MitoQ and SS31) significantly protected against HOCl-induced mitochondrial damage and cell death at concentrations >or=25 nM. Our study highlights the potential application of mitochondria-specific targeted antioxidants for the prevention of cellular dysfunction and cell death under conditions of chlorinative stress, as occurs during chronic inflammation.
Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Universities of Exeter and Plymouth, St Luke's Campus, Exeter, Devon, England. matt.whiteman@pms.ac.uk
Matthew
M
Whiteman
Jeremy P E
JP
Spencer
Hazel H
HH
Szeto
Jeffrey S
JS
Armstrong
D000975:Antioxidants / Q000494:pharmacology*; D006801:Humans; D006997:Hypochlorous Acid / Q000633:toxicity*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D013481:Superoxides; D006997:Hypochlorous Acid