Isofurans: Discovery, characterization, and novel insights into oxygen-mediated lipid peroxidation in human disease

Oxidative stress is a process that has been implicated in an ever-increasing number of pathological processes and human disease states. The analysis of lipid peroxidation products is one of the most robust methods currently available for assessing the role of oxidative stress in disease states. Herein is described the discovery and characterization of isofurans, a novel class of lipid peroxidation products, and their involvement in human pathology. The structural characterization of isofurans, as products of the free radical oxidation of arachidonic acid that contain a substituted tetrahydrofuran ring, is described in detail. The positive relationship between isofuran formation and oxygen concentration is then established in in vitro and in vivo models. The utility of isofurans as an index of oxidative stress in disease states where oxygen concentrations are perturbed is then demonstrated through an analysis of brain tissue from patients diagnosed with Parkinson's disease. The role of oxygen itself as both a cause and modulator of oxidative injury is then explored using an animal model of oxygen toxicity. Parallels to human oxygen toxicity, oxidative lung injury, and the clinical relevance of these investigations are discussed. Finally, avenues of future inquiry are outlined and the possible overall implications for human physiology and pathophysiology are described.