Alleviation of paraquat-induced lung injury by pretreatment with bifunctional liposomes containing alpha-tocopherol and glutathione.
Reactive oxygen species are known to play a key role in the development of acute lung injury, and such injury can be alleviated by pretreating the lung with a suitable antioxidant preparation. In this study, we evaluated and compared the antioxidant efficacy of two liposomal preparations: liposomes containing only alpha-tocopherol versus bifunctional liposomes containing both alpha-tocopherol and glutathione (GSH). alpha-Tocopherol liposomes (2 mg alpha-tocopherol/animal) or liposomes containing both alpha-tocopherol and GSH (2 mg alpha-tocopherol and 10 mumol GSH/animal) were intratracheally instilled into the lungs of rats 30 min prior to a challenge with paraquat dichloride (30 mg/kg, i.p.); animals were killed 24 hr post-paraquat challenge. Lungs of paraquat-challenged animals were damaged extensively as evidenced by increases in lung weight, indicative of edema, and decreases in lung activities of angiotensin converting enzyme (ACE) and alkaline phosphatase (AKP), indicative of endothelial and alveolar type II epithelial cell injuries, respectively. While the pretreatment of rats with alpha-tocopherol liposomes or liposomes containing both alpha-tocopherol and GSH significantly attenuated paraquat-induced changes in lung ACE activity to more or less the same extent, the bifunctional liposomal preparation conferred additional protection to alveolar type II epithelial cells, as evidenced by a significantly higher pulmonary AKP activity. Our results also showed that both liposomal preparations failed to ameliorate paraquat-induced lung edema despite a significant protection of pulmonary endothelial cells, suggesting that paraquat-induced edema formation may be independent of endothelial cell damage. In conclusion, liposome-associated antioxidants can protect the lung against an oxidant challenge, and the extent of protection appears to be related to the characteristics of each antioxidant formulation.
Suntres
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Operational Medicine Sector, Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada.
Shek
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D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D015415:Biomarkers; D005978:Glutathione / Q000008:administration & dosage / Q000494:pharmacology*; D006540:Herbicides / Q000633:toxicity*; D008081:Liposomes; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D055370:Lung Injury; D008297:Male; D010269:Paraquat / Q000633:toxicity*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology*
D000975:Antioxidants; D015415:Biomarkers; D006540:Herbicides; D008081:Liposomes; D017382:Reactive Oxygen Species; D014810:Vitamin E; D000469:Alkaline Phosphatase; D007703:Peptidyl-Dipeptidase A; D005978:Glutathione; D010269:Paraquat