Many diseases are associated with oxidative stress, which occurs when the production of reactive oxygen species (ROS) overwhelms the scavenging ability of an organism. Here, we evaluated the carbon nanoparticle antioxidant properties of poly(ethylene glycolated) hydrophilic carbon clusters (PEG-HCCs) by electron paramagnetic resonance (EPR) spectroscopy, oxygen electrode, and spectrophotometric assays. These carbon nanoparticles have 1 equivalent of stable radical and showed superoxide (O 2•− ) dismutase-like properties yet were inert to nitric oxide (NO • ) as well as peroxynitrite (ONOO − ). Thus, PEG-HCCs can act as selective antioxidants that do not require regeneration by enzymes. Our steadystate kinetic assay using KO 2 and direct freeze-trap EPR to follow its decay removed the rate-limiting substrate provision, thus enabling determination of the remarkable intrinsic turnover numbers of O 2 •− to O 2 by PEG-HCCs at >20,000 s −1 . The major products of this catalytic turnover are O 2 and H 2 O 2 , making the PEG-HCCs a biomimetic superoxide dismutase.superoxide | antioxidant | carbon nanoparticles | hydrophilic carbon clusters | superoxide dismutase mimetic R eactive oxygen species (ROS), such as superoxide (O 2 •− ), hydrogen peroxide (H 2 O 2 ), organic peroxides, and hydroxyl radical ( • OH), are a consequence of aerobic metabolism (1, 2). These ROS are necessary for the signaling pathways in biological processes (3, 4) such as cell migration, circadian rhythm, stem cell proliferation, and neurogenesis (5). In healthy systems, ROS are efficiently regulated by the defensive enzymes superoxide dismutase (SOD) and catalase, and by antioxidants such as glutathione, vitamin A, ascorbic acid, uric acid, hydroquinones, and vitamin E (6). When the production of ROS overwhelms the scavenging ability of the defense system, oxidative stress occurs, causing dysfunctions in cell metabolism (7)(8)(9)(10)(11)(12)(13)(14)(15)(16).In addition to ROS, reactive nitrogen species (RNS) such as nitric oxide (NO • ), nitrogen dioxide, and dinitrogen trioxide can be found in all organisms. NO • can act as an oxidizing or reducing agent depending on the environment (17), is more stable than other radicals (half-life 4-15 s) (18), and is synthesized in small amounts in vivo (17)(18)(19)(20)(21)(22). NO • is a potent vasodilator and has an important role in neurotransmission and cytoprotection (17,18,22,23). Owing to its biological importance and the low concentration found normally in vivo, it is often important to avoid alteration of NO • levels in biological systems to prevent aggravation of acute pathologies including ischemia and reperfusion.One way to treat these detrimental pathologies is to supply antioxidant molecules or particles that renormalize the disturbed oxidative condition. We recently developed a biocompatible carbon nanoparticle, the poly(ethylene glycolated) hydrophilic carbon cluster (PEG-HCC), which has shown ability to scavenge oxyradicals and protect against oxyradical damage in rodent models and thus far h...
Injury to the neurovasculature is a feature of brain injury and must be addressed to maximize opportunity for improvement. Cerebrovascular dysfunction, manifested by reduction in cerebral blood flow (CBF), is a key factor that worsens outcome after traumatic brain injury (TBI), most notably under conditions of hypotension. We report here that a new class of antioxidants, poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), which are nontoxic carbon particles, rapidly restore CBF in a mild TBI/hypotension/resuscitation rat model when administered during resuscitation—a clinically relevant time point. Along with restoration of CBF, there is a concomitant normalization of superoxide and nitric oxide levels. Given the role of poor CBF in determining outcome, this finding is of major importance for improving patient health under clinically relevant conditions during resuscitative care and it has direct implications for the current TBI/hypotension war-fighter victims in the Afghanistan and Middle East theaters. The results also have relevancy in other related acute circumstances such as stroke and organ transplantation.
A cytochrome c-coated platinized carbon electrode was utilized to detect superoxide generated by the brain during hypoxia/hypercarbia, focal ischemia, and reperfusion and following fluid percussion brain injury with and without hemorrhagic hypotension and reperfusion in the rat. All three of these forms of brain injury were associated with an increase in the superoxide signal. The cytochrome c electrode proved to be sensitive and responsive enough for minute-by-minute measurement of superoxide generation by brain tissue.
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