Liposomal alpha-tocopherol alleviates the progression of paraquat-induced lung damage.
The present study was carried out to investigate the efficacy of liposome-associated alpha-tocopherol in treating pulmonary damage caused by paraquat exposure. alpha-Tocopherol liposomes (8 mg alpha-tocopherol/kg body weight) or plain liposomes were intratracheally instilled into the lungs of rats 24 h after paraquat treatment (20 mg/kg, ip); treated animals were killed 8, 24 or 48 h after administration of the liposomal preparations. Lungs of animals exposed to paraquat were extensively damaged as evidenced by an increase in lung weight and decreases in pulmonary angiotensin converting enzyme and alkaline phosphatase activities. Also, paraquat treatment resulted in a significant reduction in glutathione (GSH) concentration in the lung and an elevation in microsomal lipid peroxidation levels, as measured by the formation of diene conjugates. Treatment of paraquat-injected rats with plain liposomes did not significantly alter paraquat-induced changes of all parameters examined. On the other hand, treatment of rats with alpha-tocopherol liposomes, 24 h after paraquat administration, resulted in a significant increase in pulmonary alpha-tocopherol concentrations as well as a reduction in paraquat-induced changes in lipid peroxidation, GSH concentration, and lung angiotensin converting enzyme and alkaline phosphatase activities. The results of the present study suggest that alpha-tocopherol, administered directly to the lung in a liposomal form, may serve as a potentially effective pharmacological agent in the treatment of paraquat-induced lung injury.
Suntres
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Operational Medicine Division, Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada.
Shek
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D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000592:standards; D004781:Environmental Exposure; D005978:Glutathione / Q000378:metabolism; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000188:drug therapy; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010269:Paraquat / Q000008:administration & dosage / Q000633:toxicity*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D004337:Drug Carriers; D008081:Liposomes; D014810:Vitamin E; D000469:Alkaline Phosphatase; D007703:Peptidyl-Dipeptidase A; D005978:Glutathione; D010269:Paraquat