Prevention of chronic pulmonary oxygen toxicity in young rats with liposome-encapsulated catalase administered intratracheally.
The lungs and hearts of young rats exposed to 100% oxygen (O2) for 8 days (27 to 35 days of age) were studied following recovery in room air at 60 days of age using morphometric, biochemical, and physiological techniques. In an attempt to prevent chronic oxygen toxicity 153 rats had transtracheal catheters surgically implanted and were treated during the O2 exposure with daily intratracheal injections of liposome-encapsulated superoxide dismutase (SOD) and/or catalase (CAT). Oxygen exposure in this model results in chronic cardiopulmonary alterations which include pulmonary hypertension, right ventricular hypertrophy, and a decrease in number of pulmonary arterioles 25 to 50 microns in diameter with increased muscularization of their walls. The volume densities of the parenchyma, parenchymal air space, and the alveolar space are increased, while that of the combined alveolar ductal and respiratory bronchiolar space is decreased. Daily intratracheal administration of liposome-encapsulated CAT (160 U) during the O2 exposure prevented these chronic changes. Liposome-encapsulated SOD (110 U) or SOD (50 U) + CAT (70 U) did not appear to have a preventive effect. During the first 3 to 5 days following oxygen exposure the lung tissue enzymes SOD, CAT, and glutathione peroxidase markedly increased. We conclude that in the young rat animal model liposome-encapsulated CAT (160 U) given intratracheally during the period of O2 exposure is safe and will prevent the chronic vascular and parenchymal damage due to oxygen toxicity.
Thibeault
D W
DW
University of Missouri-Kansas City School of Medicine, School of Basic Life Sciences, Missouri.
Rezaiekhaligh
M
M
Mabry
S
S
Beringer
T
T
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D002374:Catalase / Q000008:administration & dosage* / Q000378:metabolism; D004337:Drug Carriers; D005979:Glutathione Peroxidase / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000517:prevention & control*; D008081:Liposomes; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010100:Oxygen / Q000009:adverse effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000378:metabolism
D000975:Antioxidants; D004337:Drug Carriers; D008081:Liposomes; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D010100:Oxygen