Polyethylene glycol-conjugated superoxide dismutase protects rats against oxygen toxicity.

Abstract

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.

• Authors: G Tang, J E White, R J Gordon, P D Lumb, M F Tsan
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 74 Issue 3 Pg. 1425-31 (Mar 1993) ISSN: 8750-7587 [Print] United States
• PMID: 8482686 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antioxidants
• Tumor Necrosis Factor-alpha
• Polyethylene Glycols
• Superoxide Dismutase
• Oxygen

Topics

• Administration, Inhalation
• Animals
• Antioxidants (metabolism)
• Injections, Intraperitoneal
• Injections, Intravenous
• Lung Injury
• Male
• Oxygen (antagonists & inhibitors, toxicity)
• Polyethylene Glycols (administration & dosage, pharmacology)
• Pulmonary Alveoli (cytology, drug effects)
• Rats
• Rats, Sprague-Dawley
• Superoxide Dismutase (administration & dosage, pharmacology)
• Therapeutic Irrigation
• Trachea (physiology)
• Tumor Necrosis Factor-alpha (pharmacology)