Pulmonary metabolism of reactive oxygen species.
Preexposure of rats to sublethal levels of hyperoxia or ozone reduces morbidity and mortality when the animals are subsequently exposed to lethal levels of either oxidant stress. Lung homogenates and isolated type II pneumocytes from rats exposed to these oxidant stresses demonstrate enhanced antioxidant enzyme activities. Antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase are responsible for the detoxification of partially reduced oxygen species, superoxide and hydrogen peroxide, to less reactive states. Potential pulmonary cellular loci of partially reduced oxygen include mitochondrial NADH dehydrogenase, endoplasmic reticulum-derived NADPH cytochrome c reductase, and cytosolic xanthine oxido reductase. Thus partially reduced oxygen species are hypothesized to mediate hyperoxia and ozone-induced pulmonary damage. This damage may be attenuated by enhanced intracellular antioxidant enzyme activities. Pharmacologic augmentation of pulmonary antioxidant enzymes may be accomplished via intratracheal or intravascular delivery of liposomes containing antioxidant enzymes. Rats pretreated with liposomes containing both superoxide dismutase and catalase, when subsequently exposed to lethal levels of hyperoxia, demonstrate enhanced survival compared with control animals or with animals treated with control liposomes or native antioxidant enzymes. Finally, knowledge obtained from in vitro investigations optimizing liposomal delivery to specific pulmonary cell types may further aid in reducing in vivo pulmonary damage to hyperoxia and ozone.
Panus
P C
PC
Department of Anesthesiology, University of Alabama, Birmingham 35294.
Shearer
J
J
Freeman
B A
BA
D000222:Adaptation, Physiological; D000818:Animals; D002374:Catalase / Q000008:administration & dosage / Q000494:pharmacology; D004337:Drug Carriers; D006801:Humans; D008081:Liposomes; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism
D004337:Drug Carriers; D008081:Liposomes; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D010100:Oxygen