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 intraveno us administration of liposomal alpha-tocopherol can result in a signif icant localization of the antioxidant in the injured lung. Male Spragu e-Dawley rats were injected with paraquat dichloride (20 mg/kg, ip.) a nd 4, 24 or 48 h later, they were given an intravenous injection of a liposomal alpha-toco-pherol preparation (20 mg alpha-tocopherol in 128 mu moles liposomal Lipid/kg) labelled with [C-14]dipalmitoylphosphati dylcholine (DPPC) and [H-13]alpha-tocopherol. Animals were killed and their lungs removed for analysis 24 h after liposomal treatment. To de monstrate 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 cr-tocopherol; animals were then killed 24 h a fter liposomal alpha-tocopherol treatment, The intraperitoneal injecti on of paraquat dichloride resulted in time- and dose-dependent decreas es in angiotensin converting enzyme and alkaline phosphatase activitie s suggesting that the toxicant injures both the capillary endothelial cells and alveolar type II epithelial cells, respectively, The recover y of intravenously administered radioactive a-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 t o the lung, resulting in a difference of pulmonary delivery by as much as 2-3 fold compared to that in a normal lung, The H-3/C-14 ratio, re presenting the recovery of [H-3]alpha-tocopherol and [C-14]liposomes, was practically constant and there was a linear relationship between t he measurable lung injury index and the corresponding recovery of radi olabelled 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.