摘要
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 (L-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 α-tocopherol liposomes (8 mg α-tocopherol/kg body weight) were administered intratracheally to animals 24 h prior to an intraperitoneal injection of paraquat dichloride (20 mg/kg) and rats wefe 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 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 (t-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 α-tocopherol appears to protect the lung against some of the toxic effects of paraquat
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 (L-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 α-tocopherol liposomes (8 mg α-tocopherol/kg body weight) were administered intratracheally to animals 24 h prior to an intraperitoneal injection of paraquat dichloride (20 mg/kg) and rats wefe 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 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 (t-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 α-tocopherol appears to protect the lung against some of the toxic effects of paraquat
