Polyethylene glycol-attached antioxidant enzymes decrease pulmonary oxygen toxicity in rats.
When exposed continuously to hyperoxia (100% O2, 760 Torr barometric pressure), rats pretreated with polyethylene glycol (PEG)-attached superoxide dismutase and catalase (PEG-SOD + PEG-CAT) lived longer (79.1 + 7.6 h) than rats pretreated with saline (60.7 +/- 2.1 h) or PEG-inactivated-SOD + PEG-inactivated-CAT (62.3 +/- 1.6 h). Rats pretreated with PEG-SOD + PEG-CAT also had less hyperoxia-induced acute oxidative edematous lung injury, as assessed by increases in lung oxidized glutathione (GSSG) contents, pleural effusions, and lung lavage albumin concentrations than saline-pretreated rats. Rats pretreated with the long-lived conjugates PEG-inactivated-SOD + PEG-inactivated-CAT or PEG-albumin also had decreased acute oxidative edematous lung injury compared with rats pretreated with PEG, SOD + CAT + PEG, SOD + CAT, or saline. In vitro studies suggested that PEG itself may have contributed to protection by scavenging hydroxyl radical (.OH) but not superoxide (O2-.) or H2O2. Compared with more effective endogenous (via preexposure to hypoxia) or exogenous (via liposomes) means for increasing lung antioxidant enzymes, PEG enzymes are less protective against lung injury from continuous hyperoxia.
White
C W
CW
Department of Pediatrics, University of Colorado School of Medicine, Denver 80262.
Jackson
J H
JH
Abuchowski
A
A
Kazo
G M
GM
Mimmack
R F
RF
Berger
E M
EM
Freeman
B A
BA
McCord
J M
JM
Repine
J E
JE
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D002374:Catalase / Q000008:administration & dosage*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D055370:Lung Injury; D008297:Male; D010100:Oxygen; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011654:Pulmonary Edema / Q000517:prevention & control; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000008:administration & dosage*; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D006878:Hydroxides; C070295:catalase-polyethylene glycol; D013481:Superoxides; D017665:Hydroxyl Radical; D011092:Polyethylene Glycols; D002374:Catalase; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; D005978:Glutathione; D010100:Oxygen; D019803:Glutathione Disulfide