Suntres Z E, Shek P N
Operational Medicine Division, Defence and Civil Institute of Environmental Medecine, North York, Ontario, Canada.
Biomed Environ Sci. 1995 Dec;8(4):289-300.
Paraquat is a broad-spectrum herbicide known to produce lung injury via oxidative stress-mediated mechanisms. Different pharmacological strategies have been explored to reduce the formation of these reactive oxygen species and/or prevent their toxic effects in the treatment of paraquat poisoning. The present study was carried out to investigate whether the antioxidant alpha-tocopherol, incorporated into liposomes and delivered directly to the lungs of rats, could protect the organ against the long-term toxic effects of paraquat. Plain liposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or alpha-tocopherol liposomes (8 mg alpha-tocopherol/kg body weight) were administered intratracheally to animals 24 h prior to an intraperitoneal injection of paraquat dichloride (20 mg/kg) and rats were killed 0, 1, 4, 6, 8, 10, 12, 16, 19 or 24 days after paraquat treatment. Results of this study showed that lungs of animals treated with paraquat were extensively damaged, as evidenced by significant increases in lung weight and decreases in lung angiotensin converting enzyme (ACE) and alkaline phosphatase enzyme (AKP) activities. Moreover, paraquat treatment: resulted in a significant reduction in the number of neutrophils in the blood of rats with a concurrent increase in the pulmonary myeloperoxidase activity, suggestive of neutrophil infiltration in the lungs of treated animals. Pretreatment of rats with liposomes alone did not significantly alter the paraquat-induced changes of all parameters examined. On the other hand, pretreatment of rats with alpha-tocopherol liposomes, 24 h prior to paraquat challenge, attenuated paraquat-induced changes in ACE, AKP and myeloperoxidase activities but failed to prevent increases in lung weight. Thus, pretreatment of rats with liposome-associated alpha-tocopherol appears to protect the lung against some of the toxic effects of paraquat.
百草枯是一种广谱除草剂，已知可通过氧化应激介导的机制导致肺损伤。人们探索了不同的药理学策略来减少这些活性氧的形成和/或在百草枯中毒治疗中预防其毒性作用。本研究旨在调查包裹在脂质体中并直接递送至大鼠肺部的抗氧化剂α-生育酚是否能保护该器官免受百草枯的长期毒性影响。在腹腔注射二氯化百草枯（20 mg/kg）前24小时，将普通脂质体（由二棕榈酰磷脂酰胆碱，DPPC组成）或α-生育酚脂质体（8 mgα-生育酚/千克体重）经气管内给予动物，并在百草枯处理后0、1、4、6、8、10、12、16、19或24天处死大鼠。本研究结果表明，百草枯处理的动物肺部受到广泛损伤，肺重量显著增加以及肺血管紧张素转换酶（ACE）和碱性磷酸酶（AKP）活性降低证明了这一点。此外，百草枯处理导致大鼠血液中中性粒细胞数量显著减少，同时肺髓过氧化物酶活性增加，提示处理动物肺部有中性粒细胞浸润。单独用脂质体预处理大鼠并未显著改变百草枯诱导的所有检测参数的变化。另一方面，在百草枯攻击前24小时用α-生育酚脂质体预处理大鼠，可减轻百草枯诱导的ACE、AKP和髓过氧化物酶活性变化，但未能阻止肺重量增加。因此，用与脂质体相关的α-生育酚预处理大鼠似乎可保护肺免受百草枯的一些毒性作用。
