OxyFile #399

The cascade mechanism to explain ozone toxicity: the role of lipid 
ozonation products.

Pryor WA; Squadrito GL; Friedman M

Biodynamics Institute, Louisiana State University, Baton Rouge, 

Free Radic Biol Med, 19: 6, 1995 Dec, 935-41


Ozone is so reactive that it can be predicted to be entirely 
consumed as it passes through the first layer of tissue it 
contacts at the lung/air interface. This layer includes the lung 
lining fluid (tracheobronchial surface fluid and alveolar and 
small airway lining fluid) and, where the lung lining fluid is 
thin or absent, the membranes of the epithelial cells that line 
the airways. Therefore, the biochemical changes that follow the 
inhalation of ozone must be relayed into deeper tissue strat by a 
cascade of ozonation products. Lipid ozonation products (LOP) are 
suggested to be the most likely species to act as signal 
transduction molecules. This is because unsaturated fatty acids 
are present in the lipids in both the lung lining fluid and in 
pulmonary cell bilayers, and ozone reacts with unsaturated fatty 
acids to produce ozone-specific products. Further, lipid ozonation 
products are finite in number, have structures that are 
predictable from the Criegee ozonation mechanism, and are small, 
diffusible, stable (or metastable) molecules. Preliminary data 
show that individual LOP cause the activation of specific lipases, 
which trigger the release of endogenous mediators of inflammation.