Real-time quantification of oxidative stress and the protective effect of nitroxide antioxidants

Rayner, Cassie L., Bottle, Steven E., Gole, Glen A., Ward, Michael S. and Barnett, Nigel L. (2015) Real-time quantification of oxidative stress and the protective effect of nitroxide antioxidants. Neurochemistry International, 92 1-12. doi:10.1016/j.neuint.2015.11.003


Author Rayner, Cassie L.
Bottle, Steven E.
Gole, Glen A.
Ward, Michael S.
Barnett, Nigel L.
Title Real-time quantification of oxidative stress and the protective effect of nitroxide antioxidants
Journal name Neurochemistry International   Check publisher's open access policy
ISSN 1872-9754
0197-0186
Publication date 2015-08-28
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.neuint.2015.11.003
Open Access Status Not Open Access
Volume 92
Start page 1
End page 12
Total pages 12
Place of publication London, United Kingdom
Publisher Elsevier
Collection year 2016
Language eng
Formatted abstract
Nitroxides have been exploited as profluorescent probes for the detection of oxidative stress. In addition, they deliver potent antioxidant action and attenuate reactive oxygen species (ROS) in various models of oxidative stress, with these results ascribed to superoxide dismutase or redox and radical-scavenging actions. Our laboratory has developed a range of novel, biostable, isoindoline nitroxide-based antioxidants, DCTEIO and CTMIO. In this study we compared the efficiency of these novel compounds as antioxidant therapies in reducing ROS both in vivo (rat model) and in vitro (661W photoreceptor cells), with the established antioxidant resveratrol. By assessing changes in fluorescence intensity of a unique redox-responsive probe in the rat retina in vivo, we evaluated the ability of antioxidant therapy to (1) ameliorate ROS production and (2) reverse the accumulation of ROS after complete, acute ischemia followed by reperfusion (I/R). I/R injury induced a marked decrease in fluorescence intensity over 60 min of reperfusion, which was successfully ameliorated with each of the antioxidants. DCTEIO and CTMIO reversed the accumulation of ROS when administered intraocularly post ischemic insult, whereas, the effect of resveratrol was not significant. We also investigated our novel agents’ capacity to prevent ROS-mediated metabolic dysfunction in the 661W photoreceptor cell line. Cellular stress induced by the oxidant, tert-butyl hydroperoxide, resulted in a loss of spare mitochondrial respiratory capacity (SMRC) and in the extracellular acidification rate in 661W cells. DCTEIO antioxidant administration successfully reduced the loss of SMRC. Together, these findings show we can quantify dynamic changes in cellular oxidative status in vivo and suggest that nitroxide-based antioxidants may provide greater protection against oxidative stress than the current state-of-the-art antioxidant treatments for ROS-mediated diseases.
Keyword Antioxidant
Ischemia
Retina
Nitroxide
Neuroprotection
Radical
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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