Intratracheally administered liposomal alpha-tocopherol protects the lung against long-term 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 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.
Suntres
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Operational Medicine Division, Defence and Civil Institute of Environmental Medecine, North York, Ontario, Canada.
Shek
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D000393:Air Pollutants / Q000037:antagonists & inhibitors / Q000506:poisoning*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004337:Drug Carriers; D006540:Herbicides / Q000037:antagonists & inhibitors / Q000506:poisoning*; D007442:Intubation, Intratracheal; D008081:Liposomes; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000506:poisoning*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014810:Vitamin E / Q000008:administration & dosage*
D000393:Air Pollutants; D004337:Drug Carriers; D006540:Herbicides; D008081:Liposomes; D014810:Vitamin E; D010269:Paraquat