Antioxidants and antioxidant enzymes protect against pulmonary oxygen toxicity in the rabbit.
Two major lines of defense exist against oxidant lung injury: tissue antioxidants and antioxidant enzymes. We studied pretreatment with the antioxidants, vitamin E and butylated hydroxyanisole (BHA), and the antioxidant enzymes, superoxide dismutase (SOD) and catalase, in rabbits exposed to 100% O2 for 48 h. BHA (200 mg/kg ip) or vitamin E (50-100 mg/kg po) were given for 2 or 3 days, respectively, before O2 exposure. Combined therapy with polyethylene glycol- (PEG) conjugated SOD (12 mg/kg) and catalase (200,000 U/kg) was given intraperitoneally 1 h before and 24 h after beginning 100% O2. Hyperoxia significantly increased the pulmonary content of malondialdehyde, indicating enhanced lipid peroxidation. One hundred percent O2 also increased lung weight gain and alveolar-capillary permeability to aerosolized 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA, 500 mol wt) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt). Pretreatment with vitamin E, BHA, or the combination of PEG-SOD and PEG-catalase prevented the increase in malondialdehyde, lung weight gain, and alveolar-capillary permeability caused by hyperoxia. These results indicate that augmenting either tissue antioxidants or antioxidant enzymes can prevent the pulmonary injury caused by 48 h of 100% O2 in rabbits.
Jacobson
J M
JM
Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Michael
J R
JR
Jafri
M H
MH
Gurtner
G H
GH
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D002374:Catalase / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D055370:Lung Injury; D008315:Malondialdehyde / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; C070295:catalase-polyethylene glycol; D014810:Vitamin E; D002083:Butylated Hydroxyanisole; D011092:Polyethylene Glycols; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; D010100:Oxygen