The pulmonary uptake of intravenously administered liposomal alpha-tocopherol is augmented in acute lung injury.
The present study was carried out to investigate whether the intravenous administration of liposomal alpha-tocopherol can result in a significant localization of the antioxidant in the injured lung. Male Sprague-Dawley rats were injected with paraquat dichloride (20 mg/kg, ip.) and 4, 24 or 48 h later, they were given an intravenous injection of a liposomal alpha-tocopherol preparation (20 mg alpha-tocopherol in 128 mumoles liposomal lipid/kg) labelled with [14C]dipalmitoylphosphatidylcholine (DPPC) and [3H]alpha-tocopherol. Animals were killed and their lungs removed for analysis 24 h after liposomal treatment. To demonstrate whether the extent of uptake of radioactive alpha-tocopherol liposomes was directly related to the extent of residual lung injury, additional groups of animals were also injected with higher doses (30 and 40 mg/kg body weight) of paraquat dichloride and 48 h later, were treated with liposomal alpha-tocopherol; animals were then killed 24 h after liposomal alpha-tocopherol treatment. The intraperitoneal injection of paraquat dichloride resulted in time- and dose-dependent decreases in angiotensin converting enzyme and alkaline phosphatase activities suggesting that the toxicant injures both the capillary endothelial cells and alveolar type II epithelial cells, respectively. The recovery of intravenously administered radioactive alpha-tocopherol in the lungs of saline-treated animals was found to be about 2% of the initial dose 24 h post-liposomal treatment. However, in paraquat-treated animals, there was an increased localization of the labelled alpha-tocopherol to the lung, resulting in a difference of pulmonary delivery by as much as 2-3 fold compared to that in a normal lung. The 3H/14C ratio, representing the recovery of [3H]alpha-tocopherol and [14C]liposomes, was practically constant and there was a linear relationship between the measurable lung injury index and the corresponding recovery of radiolabelled alpha-tocopherol in the lung. Our results appear to suggest that the residual pulmonary injury augments the delivery of liposomal alpha-tocopherol to the lung.
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
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D004337:Drug Carriers; D007275:Injections, Intravenous; D008081:Liposomes / Q000493:pharmacokinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000378:metabolism*; D014810:Vitamin E / Q000008:administration & dosage* / Q000493:pharmacokinetics
D004337:Drug Carriers; D008081:Liposomes; D014810:Vitamin E; D000469:Alkaline Phosphatase; D007703:Peptidyl-Dipeptidase A