PULMONARY UPTAKE OF LIPOSOME-ASSOCIATED ALPHA-TOCOPHEROL FOLLOWING INTRATRACHEAL INSTILLATION IN RATS

This study examined the uptake and subcellular distribution of alpha-t ocopherol in the lung following intratracheal instillation of liposome -associated alpha-tocopherol in rats. The liposomal suspension was com posed of dipalmitoylphosphatidylcholine (DPPC) and alpha-tocopherol (m olar ratio 7:3), labelled with [H-3]alpha-tocopherol and [C-14]cholest rol. Following intratracheal administration of the liposomal preparati on (2 mg alpha-tocopherol/animal), the recovery of [H-3]alpha-tocopher ol in the lung was (87% of initial dose) 1 h after treatment; thereaft er alpha-tocopherol levels remained relatively high (no less than 73% of initial dose) for the rest of the 72-h experimental period. This tr eatment effect resulted in a 16-fold increase in pulmonary total alpha -tocopherol concentration 72 h post-instillation. No radioactivity was detected in the blood, liver, kidney, pancreas, spleen and heart of a nimals during the 72-h experimental period. [H-3]alpha-Tocopherol was recovered largely from cytosolic (45%) and nuclear (36%) fractions of lung and to a lesser extent, from microsomal (11%) and mitochondrial ( 9%) fractions. Chromatographic analysis of the subcellular fractions r evealed that [H-3]alpha-tocopherol was co-eluted with C-14-labelled li posomal lipids. Our in-vitro study, involving the incubation of Fe3+-A DP (a pro-oxidant) with mitochondrial or microsomal fractions isolated from lung tissues of animals treated with liposome-associated alpha-t ocopherol, provided evidence that alpha-tocopherol levels present in t he membranes of these subcellular fractions were sufficient to protect against oxidant-induced lipid peroxidation. alpha-Tocopherol in the r at lung can be greatly increased by the intratracheal instillation of alpha-tocopherol entrapped in DPPC-liposomes, suggesting that this lip osomal preparation may be used as an effective prophylactic agent agai nst oxidant-induced lung injury.