Pulmonary Uptake of Liposome-associated α-Tocopherol Following Intratracheal Instillation in Rats

This study examined the uptake and subcellular distribution of alpha-tocopherol in the lung following intratracheal instillation of liposome-associated alpha-tocopherol in rats. The liposomal suspension was composed of dipalmitoylphosphatidylcholine (DPPC) and alpha-tocopherol (molar ratio 7:3), labelled with [3H]alpha-tocopherol and [14C]cholesterol. Following intratracheal administration of the liposomal preparation (2 mg alpha-tocopherol/animal), the recovery of [3H]alpha-tocopherol in the lung was maximal (87% of initial dose) 1 h after treatment; thereafter, alpha-tocopherol levels remained relatively high (no less than 73% of initial dose) for the rest of the 72-h experimental period. This treatment 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 animals during the 72-h experimental period. [3H]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 revealed that [3H]alpha-tocopherol was co-eluted with 14C-labelled liposomal lipids. Our in-vitro study, involving the incubation of Fe(3+)-ADP (a pro-oxidant) with mitochondrial or microsomal fractions isolated from lung tissues of animals treated with liposome-associated alpha-tocopherol, provided evidence that alpha-tocopherol levels present in the membranes of these subcellular fractions were sufficient to protect against oxidant-induced lipid peroxidation.(ABSTRACT TRUNCATED AT 250 WORDS)