Therapeutic Catalytic Nanoantioxidants Derived From Activated Charcoal
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Introduction: Our laboratories focus is synthesis of potential carbon nanoparticle (CNP) therapeutics for acute injury. To enhance the likelihood of regulatory approval, we tested whether medicinal grade activated charcoal (AC) could serve as the initial source. Taken up avidly and localizing to organelles, e.g. mitochondria, CNPs broad redox potential could facilitate electron transfer. Here, we test whether CNPs from AC are cytoprotective in a brain endothelial cell line and their restoration of cerebral autoregulation in a traumatic brain injury model. Materials and Methods: 5-30 nM oxidized AC (OAC) were synthesized from medicinal AC, treated with oleum and 90% nitric acid, then covalently PEGylated. Cell number was assessed in bEnd.3 cells incubated 18 hrs with 50 M H 2 O 2 w/wo 8 mg/L PEG-OACs. An electron transport assay was performed with NADH (e - donor) and resazurin (e - acceptor) using kinetic UV-vis spectroscopy. 2 mg/kg PEG-OACs were administered IV to rats upon resuscitation and at 200 minutes after mild fluid percussion injury model with superimposed 80 minutes of hypotensive shock, a model known to impair reperfusion. Cerebral perfusion was monitored by laser doppler flowmetry. Results: PEG-OAC improved viability (Fig. 1a; 47% vs. 80%; p=.005). Oxidation of NADH was 3.8x faster than w/o OAC (Fig. 1b). Cerebral perfusion was restored by PEG-OAC after direct cortical injury compared to PBS vehicle (n=10; Fig. 1c; p=.0008). Conclusion: PEG-OACs protect cultured cells from oxidative stress caused by H 2 O 2 , a byproduct of ischemia, exhibit electron shuttle-like properties and restore cerebral reperfusion in-vivo when given at a clinically relevant time point.
