Intratracheally Administered Liposomal alpha-Tocopherol Protects the Lung AgainstLong-Term Toxic Effects of Paraquat

摘要

Paraquat is a broad-spectrum herbicide known to produce lung injury via oxidativestress-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 tocopheral, 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 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 treatme resulted in a significant reduction in the number of neutrophils in thc blood of rats with a concurrent increase in the pulmonary myelopcroxidase 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.