Frawley 2019 Thesis

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Frawley KL (2019) Methods for assessing cytochrome c oxidase inhibitors and potential antidotes. PhD Thesis 194.

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Frawley KL (2019) PhD Thesis

Abstract: The Countermeasures Against Chemical Terrorism (CounterACT) Program, sponsored by the U.S. Department of Homeland Security, seeks to promote and support research aimed at finding new (therapeutics) pharmaceuticals that are antidotal toward toxicants considered likely to pose significant terrorist threat. More specifically, this means countermeasures to toxicants that can be easily prepared from readily available precursors in quantities suitable for inflicting mass casualties on civilian and/or military targets. The challenge to Public Health issued by the CounterACT program is to identify and develop antidotes to any such toxicants deemed to be of particular concern, including the mitochondrial poisons sulfide, cyanide and azide. Ideally, in addition to efficacy, the antidotes should be stable enough for stockpiling and safe enough for self-administration. Herein, various biological systems mimicking some relevant aspects of acute poisonings in humans have been tested for their usefulness as experimental “models” suitable for examining toxic mechanisms and assessing the efficacies of putative antidotes. Larvae of the greater wax moth (Galleria mellonella) are shown to be a convenient and inexpensive invertebrate model for investigating the action of some mitochondrial poisons and their antidotes. The acute toxicities of sulfide, cyanide and azide have been studied together with the ameliorating effects of sodium nitrite and a cobalt-based scavenging agent. The results obtained with the larvae are compared to findings employing a cultured mammalian cell line (bovine pulmonary artery endothelial cells) and rodents (Swiss-Webster mice). The Galleria mellonella larvae are argued to be an extremely useful intact organism for (i) pre-screening putative antidotes for efficacy and (ii) circumventing any confounding effects that can arise in some studies of intracellular processes due to the presence of blood in intact vertebrates.

Keywords: G. mellonella, Wax worms, Sulfide, Cyanide, Azide, Bovine pulmonary artery endothelial cells, BPAEC Bioblast editor: Plangger M


Labels: MiParea: Respiration, Pharmacology;toxicology 


Organism: Bovines  Tissue;cell: Endothelial;epithelial;mesothelial cell  Preparation: Intact cells 



HRR: Oxygraph-2k 

2020.05