Toxicity of ozone and nitrogen dioxide to alveolar macrophages: comparative study revealing differences in their mechanism of toxic action.
The toxicity of ozone and nitrogen dioxide is generally ascribed to their oxidative potential. In this study their toxic mechanism of action was compared using an intact cell model. Rat alveolar macrophages were exposed by means of gas diffusion through a Teflon film. In this in vitro system, ozone appeared to be 10 times more toxic than nitrogen dioxide. alpha-Tocopherol protected equally well against ozone and nitrogen dioxide. It was demonstrated that alpha-tocopherol provided its protection by its action as a radical scavenger and not by its stabilizing structural membrane effect, as (1) concentrations of alpha-tocopherol that already provided optimal protection against ozone and nitrogen dioxide did not influence the membrane fluidity of alveolar macrophages and (2) neither one of the structural alpha-tocopherol analogs tested (phytol and the methyl ether of alpha-tocopherol) could provide a protection against ozone or nitrogen dioxide comparable to the one provided by alpha-tocopherol. It was concluded that reactive intermediates scavenged by alpha-tocopherol are important in the toxic mechanism of both ozone and nitrogen dioxide induced cell damage. However, further results presented strongly confirmed that the kind of radicals and/or reactive intermediates, and thus the toxic reaction mechanism involved, must be different in ozone- and nitrogen dioxide-induced cell damage. This was concluded from the observations that showed that (1) vitamin C provided significantly better protection against nitrogen dioxide than against an equally toxic dose of ozone, (2) glutathione depletion affected the cellular sensitivity toward ozone to a significantly greater extent than the sensitivity towards nitrogen dioxide, and (3) the scavenging action of alpha-tocopherol was accompanied by a significantly greater reduction in its cellular level during nitrogen dioxide exposure than during exposure to ozone. One of the possibilities compatible with the results presented in this study might be that lipid (peroxyl) free radicals formed in a radical-mediated peroxidative pathway, resulting in a substantial breakdown of cellular alpha-tocopherol, are involved in nitrogen dioxide-induced cell damage, and that lipid ozonides, scavenged by alpha-tocopherol as well, are involved in ozone-induced cell damage.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D008560:Membrane Fluidity / Q000187:drug effects; D009585:Nitrogen Dioxide / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D010587:Phagocytosis / Q000187:drug effects; D010836:Phytol / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects; D051381:Rats; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology
D014810:Vitamin E; D010836:Phytol; D010126:Ozone; D005978:Glutathione; D001205:Ascorbic Acid; D009585:Nitrogen Dioxide