Protective effect of liposome-associated alpha-tocopherol against paraquat-induced acute lung toxicity.
The present study was undertaken to investigate whether alpha-tocopherol, entrapped in liposomes and delivered directly to the lung, could protect against paraquat-induced lung damage in the rat. Plain liposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or DPPC/alpha-tocopherol liposomes were administered intratracheally to animals 24 hr prior to an intraperitoneal injection of paraquat (20 mg/kg); rats were killed 24 or 48 hr after paraquat treatment. Results of this study showed that lungs of animals treated with paraquat were damaged extensively as evidenced by an increase in lung weight and a significant reduction in lung angiotensin-converting enzyme (ACE) activity and cytochrome P450 concentration. Furthermore, paraquat treatment resulted in a significant decrease in reduced glutathione (GSH) concentrations and a marked elevation in microsomal lipid peroxidation levels as measured by the formation of diene conjugates. Pretreatment of rats with DPPC liposomes alone did not alter significantly the paraquat-induced changes of all parameters examined. On the other hand, pretreatment of rats with DPPC/alpha-tocopherol liposomes 24 hr prior to paraquat challenge resulted in a significant increase in pulmonary alpha-tocopherol concentrations and antagonized paraquat-induced changes in lipid peroxidation, GSH/GSSG ratio, lung ACE activity and cytochrome P450 concentrations. Results of this study suggested that alpha-tocopherol, delivered directly to the lung in a liposomal formulation 24 hr prior to paraquat administration, confers protection against paraquat-induced lung damage.
Suntres
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Operational Medicine Section, Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada.
Hepworth
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SR
Shek
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D015060:1,2-Dipalmitoylphosphatidylcholine; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004333:Drug Administration Routes; D004337:Drug Carriers; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010269:Paraquat / Q000633:toxicity*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea; D014810:Vitamin E / Q000008:administration & dosage* / Q000627:therapeutic use
D004337:Drug Carriers; D008081:Liposomes; D008563:Membrane Lipids; D014810:Vitamin E; D015060:1,2-Dipalmitoylphosphatidylcholine; D003577:Cytochrome P-450 Enzyme System; D007703:Peptidyl-Dipeptidase A; D005978:Glutathione; D010269:Paraquat; D019803:Glutathione Disulfide