Protective effect of liposomal alpha-tocopherol against bleomycin-induced lung injury.
The clinical use of bleomycin in the treatment of squamous cell carcinomas, lymphomas and testicular tumours has been limited by its toxic effects, the most serious being pulmonary injury. The present study was undertaken to investigate whether alpha-tocopherol, incorporated in liposomes and delivered directly to the lung, could offer protection against bleomycin-induced lung damage and fibrosis in the rat. Animals were administered, intratracheally, plain liposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or alpha-tocopherol-containing liposomes (8 mg alpha-tocopherol/kg body weight) and 30 min later, were exposed to bleomycin sulphate (4 units/kg body weight) by intratracheal instillation; treated animals were killed 21 days later. Results of this study showed that lungs of animals treated with bleomycin were seriously damaged, as evidenced by significant histological changes and increases in lung weight, lipid peroxidation, myeloperoxidase activity and hydroxyproline content as well as decreases in lung angiotensin converting enzyme (ACE) and alkaline phosphatase (AKP) activities. Pretreatment of rats with plain liposomes alone did not alter significantly the bleomycin-induced changes of all parameters examined. In contrast, pretreatment of rats with alpha-tocopherol liposomes 30 min prior to bleomycin administration resulted in little or no histological changes and conferred a significant protection against bleomycin-induced changes in edema, lipid peroxidation, hydroxyproline content, and ACE, AKP and myeloperoxidase activities. Results of this study suggested that pretreatment of rats with alpha-tocopherol liposomes can provide a significant protection against bleomycin-induced lung injury.
Suntres
Z E
ZE
Operational Medicine Sector, Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada.
Shek
P N
PN
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000008:administration & dosage / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D001761:Bleomycin / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004337:Drug Carriers; D004347:Drug Interactions; D006909:Hydroxyproline / Q000378:metabolism; D007322:Instillation, Drug; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000517:prevention & control; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D001761:Bleomycin; D014810:Vitamin E; D015060:1,2-Dipalmitoylphosphatidylcholine; D009195:Peroxidase; D000469:Alkaline Phosphatase; D007703:Peptidyl-Dipeptidase A; D006909:Hydroxyproline