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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 invesigate whether α-tocopherol, incorprated 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 lipo somes (composed of dipalmitoylphosphatidylcholine, DPPC ) or α- tocopherol-containing lipo somes (8 mg Q-tocopherol/kg body weight) and 30 min later, were exposed to bleomycin sul phate (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 se riously 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. Pre treatment of rats with plain liposomes alone did not alter significantly the bleomycin-induced changes of all parameters examined. In contrast, pretreatment of rats with α-tocopherol lipo somes 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 peroxida tion, hydroxyproline content, and ACE, AKP and myeloperoxidase activities. Results of this study suggested that pretreatment of rats with α-tocopherol liposomes can provide a significant protection against bleomycin-induced lung injury
The clinical use of bleomycin in the treatment of squamous cell carcinomas, lymphomas and testicular tumors has been limited by its toxic effects, the most serious being pulmonary injury. The present study was undertaken to invesigate whether α-tocopherol, incorprated 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 lipo somes (composed of dipalmitoylphosphatidylcholine, DPPC) or α- tocopherol-containing lipo somes (8 mg Q-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 se riously damaged, as evidenced by significant histological changes and increases in lung weight, lipid peroxidation, myeloperoxidase activity and hydroxyproline content a Pre treatment of rats with plain liposomes alone did not alter significantly the bleomycin-induced changes of all parameters examined. In contrast, pretreatment of rats with α -tocopherol lipo somes 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 peroxida tion, hydroxyproline content, and ACE, AKP and myeloperoxidase activities. Results of this research suggested that pretreatment of rats with α-tocopherol liposomes can provide a significant protection against bleomycin-induced lung injury