Abstract 253 Poster Session III, Monday, 5/3 (poster 113)

Introduction: Oxidative stress is one of the basic mechanisms of tissue injury, having been implicated in various processes such as aging, cancer, sepsis, inflammation, as well as cardiovascular and respiratory diseases. In view of the fact that PFOB attenuates oxidative lung injury in vivo, we hypothesized that this finding might be due, in part, to a direct protective effect of PFOB against reactive oxygen species-associated injury.

Method: We tested the hypothesis by studying an in vitro non-biologic system. Linoleic acid (3 mM) was emulsified into an aqueous buffer (PBS) by the detergent sodium dodecyl sulfate (SDS, 250 µM). Linoleic acid/SDS micelles were formed by agitation and sonication of the emulsion. Oxidative stress was applied by adding various concentrations (2-50 mM)of AAPH to the emulsion in the absence (control n= 4) or presence of PFOB (PFOB exposed, n= 4) at 37°C. AAPH is an azo-compound that generates peroxyl radicals at a constant rate while undergoing thermal decomposition. Malondialdehyde (MDA), a marker of lipid peroxidation, was used as an indicator of oxidation of linoleic acid micelles. Aliquots from the emulsion were reserved at various time points and the reaction was stopped by incubation with an antioxidant (BHT in methanol) prior to snap freezing in liquid nitrogen. MDA concentrations were measured in samples originated from the emulsion over a period os 4 hours.

Results: Values are means ± standard deviations of MDA concentrations (µM) over time, for the 20 mM AAPH experiment. Experiments with other concentrations of AAPH resulted in similar patterns. (Table)

Table 1 No caption available

Conclusion: PFOB attenuates oxidative damage to synthetic linoleic acid micelles from various concentrations of AAPH in a non-biologic system. This effect may account for the decreased oxidative damage observed in injury-prone tissues exposed to perfluorocarbons in vivo.

Supported, in part, by the American Lung Association- NY Affiliate, and by Alliance Pharmaceutical Corp.