ALLEVIATION OF PARAQUAT-INDUCED LUNG INJURY BY PRETREATMENT WITH BIFUNCTIONAL LIPOSOMES CONTAINING ALPHA-TOCOPHEROL AND GLUTATHIONE

Reactive oxygen species are known to pray a key role in the developmen t of acute lung injury, and such injury can be alleviated by pretreati ng the lung with a suitable antioxidant preparation In this study, we evaluated and compared the antioxidant efficacy of two liposomal prepa rations: liposomes containing only alpha-tocopherol versus bifunctiona l liposomes containing both alpha-tocopherol and glutathione (GSH). al pha-Tocopherol liposomes (2 mg alpha-tocopheror/animal) or liposomes c ontaining both alpha-tocopherol and GSH (2 mg alpha-tocopherol and 10 mu mol GSH/animal) were intratracheally instilled into the lungs of ra ts 30 min prior to a challenge with paraquat dichloride (30 mg/kg, i.p .); animals were killed 24 hr post paraquat challenge. Lungs of paraqu at-challenged animals were damaged extensively as evidenced by increas es in lung weight, indicative of edema, and decreases in lung activiti es of angiotensin converting enzyme (ACE) and alkaline phosphatase (AK P), indicative of endothelial and alveolar type II epithelial cell inj uries, respectively. While the pretreatment of rats with alpha-tocophe rol liposomes or liposomes containing both alpha-tocopherol and GSH si gnificantly attenuated paraquat-induced changes in lung ACE activity t o 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 re sults also showed that both liposomal preparations failed to ameliorat e paraquat-induced lung edema despite a significant protection of pulm onary endothelial cells, suggesting that paraquat-induced edema format ion may be independent of endothelial cell damage. In conclusion lipos ome-associated antioxidants can protect the lung against an oxidant ch allenge, and the extent of protection appears to be related to the cha racteristics of each antioxidant formulation.