Incorporation of alpha-tocopherol in liposomes promotes the retention of liposome-encapsulated glutathione in the rat lung.
The present study was undertaken to investigate whether alpha-tocopherol incorporated in liposomes could improve the retention of entrapped glutathione (GSH) in the lung following intratracheal instillation in rats. Rats were treated with a single dose of [3H]GSH entrapped in liposomes with or without 30 mol% alpha-tocopherol and killed 0, 24 or 48 h later. The retention of GSH in the lung was assessed by measuring the recovery of either 3H-label or GSH in the lung. Animals instilled with free [3H]GSH were found to retain only 2% of the administered dose at 24 h after treatment and no detectable radioactivity at 48 h. Liposome encapsulation altered the pulmonary retention of GSH with 18 and 10% of radioactivity remaining in the lung at 24 and 48 h post-treatment, respectively. The instillation of GSH encapsulated in alpha-tocopherol-containing liposomes resulted in the highest level of GSH retention in the lung, namely 37 and 30% of the administered GSH dose at 24 and 48 h, respectively. Results from Sepharose 4B column chromatography revealed that lung homogenates, obtained from rats instilled with GSH entrapped in alpha-tocopherol-containing liposomes, 24 and 48 h earlier, contained 2 eluted GSH-related components--one associated with the liposomal lipid marker in the void volume and the other as free GSH tripeptide, suggesting a slow sustained release effect mediated by the liposomal formulation. The same liposome preparation containing both alpha-tocopherol and GSH also conferred better protection against FeADP-induced lipid peroxidation than liposomes containing either alpha-tocopherol or GSH alone, indicative of a potentially effective antioxidant formulation for treating oxidative lung injury.
Suntres
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Operational Medicine Section, Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada.
Shek
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PN
D000818:Animals; D002250:Carbon Radioisotopes; D004337:Drug Carriers; D005978:Glutathione / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008081:Liposomes; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium; D014810:Vitamin E / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D004337:Drug Carriers; D008081:Liposomes; D014316:Tritium; D014810:Vitamin E; D005978:Glutathione