an animal model. We assayed lifespan and lipofuscin accumulation, two metrics of oxidative stress in the nematode Caenorhabditis elegans (C. elegans) using commercially-available (Sigma) and custom-synthesized cerium oxide nanoparticles. the commercially-available particles are considered

the custom-synthesized particles have a citric acid EDTA patented coating which acts as a stabilizer and limits

agglomeration. We will present data on the effects of varying concentrations of these particles on lifespan and lipofuscin accumulation on wild-type and superoxide-dismutase mutant worm strains. Our studies have the potential to shed insight into how the formulation influences the ultimate in vivo effects of the nanoparticle.

N-acetylcysteine Amide (NACA) Protects the Human Hepatic Cell, HepaRG, from Nitrofurantoin (NFT) Induced-Oxidative Stress Weili Fan1, Shakila Tobwala1, and Nuran Ercal1 1Missouri University of Science and Technology, United States Nitrofurantoin (NFT) is an antibiotic that is commonly used for treatment of urinary tract infection and other infections caused by Gram-negative bacteria (such as E. coli). However, it is contraindicated in oxidation-sensitive patients with glucose-6-phosphate (G-6-PD) deficiency or related genetic disorders due to the risk of intravascular hemolysis. It is well known that NFT causes oxidative stress by generating superoxide anion via redox cycle that occurs in the liver. Therefore, it is reasonable to hypothesize that administration of antioxidant would help relieve the side effects of NFT. Our previous studies showed that N-acetylcysteine (NAC) and its most permeable sister drug, N-acetylcysteine amide (NACA), work very well in many oxidatively challenged systems. in this study, we compare the protective effect of NAC and NACA against NFT-induced oxidative stress in HepaRG, a terminally-differentiated human hepatic cell line. the extent of oxidative stress and downstream damage caused by NFT was studied by measuring various oxidative stress parameters like cell viability, levels of reactive oxygen species (ROS), glutathione (GSH) level, activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione reductase (GR), as well as malondialdehyde (MDA) levels. Our results indicate that NFT causes oxidative stress in this cell line and that NACA protects HepaRG cells from oxidative damage more effectively than NAC. NAC or NACA should be given concomitantly if patients require high doses and/or for long-term treatment of NFT.

Antioxidant Potency of Sutherlandia frutescens Weili Fan1, Connor Hines1, Shakila Tobwala1, William Folk2, and Nuran Ercal1 1Missouri University of Science and Technology, United States, 2University of Missouri, United States Sutherlandia frutescens (L.) R.Br. is a versatile medicinal plant used by many in Southern Africa for treatment of stress, infections, cancer and chronic diseases, many of which involve inflammation. S. frutescens -inflammatory effect, at least

partially relies on its capability of scavenging phagocyte-derived oxidative species upon respiratory burst. (Fernandes et al, 2004, J. Ethnopharmacology 95:1-5) Therefore, S. frutescens draws our interest in studying of its antioxidant potency for possible use against oxidative-stress related chronic diseases. Extracts of S. frutescens using various solvents were prepared and their antioxidant effects were compared by determining free radical scavenging power, iron chelating power, total flavonoid and phenolic content as well as total reducing power. a hot water extract was proven to be of highest effectiveness and tested in-vitro for its protective role against tert-Butyl hydroperoxide (tBHP)-induced oxidative stress in A549 cell (human alveolar carcinoma) by determination of cell viability, reactive oxygen species (ROS), GSH level and GSH/GSSG ratio. Our results indicate that S. frutescens is of high antioxidant potency and does protect A549 cell against oxidative stress. Therefore, it might be an ideal candidate to be developed into an effective antioxidant to be used to treat numerous oxidative-stress related disorders.

EdX-17, a Novel Treatment for Sickle Cell Disease Carol Curtis1, Robert Broyles1,2, Patrick Floyd1, Robert Floyd1,2, and Austin Roth1,2 1EpimedX LLC, United States, 2Sickle Cell Cure Foundation, United States Gene regulation of developmental hemoglobin switching is thought hold to potential for therapeutic relief from all symptoms associated with Sickle Cell Disease (SCD). Reactivation of -globin expression (HbF) -globin (HbS) to produce a functional hemoglobin tetramer and eliminate the hemoglobin polymerization that is characteristic of sickled red blood cells. We have discovered a protein that regulates this developmental switch, and have identified a compound that stimulates expression of this protein. EdX-17 stimulates expression of the anti-stress factor ferritin heavy chain (FtH), which enters the nucleus of erythroid precursor cells and activates expression of -globin, producing HbF. Our studies in embryonic/K562 erythroid cells and transgenic mice demonstrate

-globin and -globin gene expression. Furthermore, treatment with EdX-17 recapitulates these results in vitro and in vivo. EdX-17 treatment reconstitutes fetal hemoglobin (HbF) in transgenic mice to levels above 25-30% - the range thought to be sufficient to ameliorate symptoms of SCD with no detectable ill effects. in fact, mice treated with EdX-17 tend to have shinier coats, and they are more alert and stronger than age-matched, untreated mice. Preliminary studies in a baboon model further indicate that EdX-17 is safe and efficacious. in vitro studies performed in primary human erythrocyte precursor cells demonstrate that doses in the picomolar range are sufficient to -globin expression. Studies are ongoing to strengthen the feasibility data and provide a basis for further development of this drug for SCD. Development of this novel therapeutic is expected to ameliorate SCD symptoms decreasing pain and morbidity, increasing lifespan, greatly improving patient quality of life, and significantly reducing treatment costs.

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