Polyethylene glycol-conjugated superoxide dismutase protects rats against oxygen toxicity.
Superoxide dismutase (SOD) has an important role in the protection against O2 toxicity. Conjugation of Cu,Zn-SOD to polyethylene glycol (PEG-SOD) prolongs its plasma half-life and facilitates its cellular uptake. However, prior studies have shown that intravenous injection of PEG-SOD does not protect animals against O2 toxicity. In this study, we demonstrated that tracheal insufflation of PEG-SOD resulted in a dose-dependent protection against O2 toxicity. Nine of 15 rats (60%) insufflated with 25,000 U PEG-SOD survived continuous 100% O2 exposure for more than 7 days compared with control rats (n = 45), all of which died within 3 days of O2 exposure (P < 0.025). In contrast, insufflation of 25,000 U SOD, 9.7 mg methoxy-PEG (equivalent to the amount of methoxy-PEG present in 25,000 U PEG-SOD), or a combination of SOD and methoxy-PEG had no protective effect. Furthermore, intravenous or intraperitoneal injection of PEG-SOD did not afford significant protection. Protection against O2 toxicity by PEG-SOD insufflation was associated with attenuated O2-induced pulmonary injury as evidenced by a reduced volume of pleural effusion. Insufflation of PEG-SOD markedly increased pulmonary SOD activity (to 300 and 370% of controls at 24 and 50 h, respectively) without affecting pulmonary catalase activity. We conclude that insufflation of PEG-SOD protects rats against O2 toxicity, possibly by enhancing pulmonary SOD activity.
Tang
G
G
Research Service, Samuel S. Stratton Department of Veterans Affairs Medical Center, Albany, New York.
White
J E
JE
Gordon
R J
RJ
Lumb
P D
PD
Tsan
M F
MF
D000280:Administration, Inhalation; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D055370:Lung Injury; D008297:Male; D010100:Oxygen / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology*; D007507:Therapeutic Irrigation; D014132:Trachea / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000975:Antioxidants; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase; D010100:Oxygen