Selected contribution: Lung hypoxia: antioxidant and antiapoptotic effects of liposomal alpha-tocopherol.
The aim of this study is to examine the antioxidant and antiapoptotic activity of liposomal alpha-tocopherol (LAT) in anesthetized rats exposed to severe hypoxia. It was shown that intratracheal application of LAT normalized lung phospholipid composition and inhibited lipid peroxidation in lung tissues, which in turn decreased lung edema and damage and improved breathing pattern, oxygen diffusion, and lung gas exchange. LAT also limited the overexpression of genes encoding hypoxia inducible factor-1alpha and both studied forms of phospholipase A(2), and it increased the power of cellular antioxidant and antiapoptotic defense by overexpressing genes encoding Mn- and Cu-Zn-cofactored superoxide dismutases, Bcl-2, and heat shock 70 proteins. The overexpression of studied caspases and their activity were downregulated, which significantly (1.6-2 times) limited apoptosis in lung cells. Finally, all these positive changes decreased mortality during hypoxia from approximately 60% in untreated animals to approximately 30% in the group of rats treated with LAT. The data obtained indicate that LAT may be useful for the correction of hypoxic lung injury.
Minko
T
T
Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA. minko@cop.rutgers.edu
Stefanov
A
A
Pozharov
V
V
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000032:analysis; D015777:Eicosanoids / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D015227:Lipid Peroxidation; D008081:Liposomes; D008171:Lung Diseases / Q000378:metabolism / Q000503:physiopathology*; D008176:Lung Volume Measurements; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D011312:Pressure; D011654:Pulmonary Edema / Q000503:physiopathology; D011659:Pulmonary Gas Exchange; D051381:Rats; D017208:Rats, Wistar; D015656:Respiratory Mechanics; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology*
D000975:Antioxidants; D015415:Biomarkers; D015777:Eicosanoids; D008081:Liposomes; D010743:Phospholipids; D024502:alpha-Tocopherol