OZONE-INDUCED LUNG TOXICITY - MEDIATED BY OZONIDES

In an in vitro study a comparison was made between the cytotoxicities of a model ozonide, methyl linoleate-9,10-ozonide (MLO), and a model peroxidative agent, cumene hydroperoxide (CumOOH), by measuring the effects of both compounds on the phagocytosing capacity of rat alveolar macrophages. Toxicity as well as detoxication characteristics of the ozonide were found to be similar to those of ozone: (1) vitamin E protected the alveolar macrophages in vitro against the ozonide, (2) glutathione (GSH) depletion enhanced the sensitivity of the cells towards the ozonide and (3) the ozonide did not enhance lipid peroxidation. This also suggests that GSH depletion, followed by lipid peroxidation, does not underlie the MLO toxicity. This was supported by the differences in protection provided by vitamin C, vitamin E and GSH. Supplementation of the macrophages with vitamin C resulted in a decrease in their sensitivity towards MLO and an increase in their sensitivity towards CumOOH. Following GSH depletion the sensitivity of the cells towards CumOOH had increased more than that towards MLO. Exposure to CumOOH led to a more extensive vitamin E depletion. The results of an in vivo study on the toxicity of MLO (in the rat) largely confirmed the findings of the in vitro study: partial contributions of vitamin E and the glutathione. system to the protection against MLO.