Pulmonary uptake of liposome-associated alpha-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)
Suntres
Z E
ZE
Operational Medicine Section, Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada.
Hepworth
S R
SR
Shek
P N
PN
D015060:1,2-Dipalmitoylphosphatidylcholine; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002250:Carbon Radioisotopes; D004337:Drug Carriers; D007322:Instillation, Drug; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D014132:Trachea; D014316:Tritium; D014810:Vitamin E / Q000008:administration & dosage / Q000493:pharmacokinetics*
D002250:Carbon Radioisotopes; D004337:Drug Carriers; D008081:Liposomes; C029936:adenosine diphosphate-ferric chelate; D014316:Tritium; D014810:Vitamin E; D015060:1,2-Dipalmitoylphosphatidylcholine; D000244:Adenosine Diphosphate