Mechanism of rat lung microsomal dysfunction induced by oxygen breathing in relation to the effect of alpha-tocopherol.
The toxic effect of high oxygen concentrations on the lung was investigated together with the effect of alpha-tocopherol (Juvela). Rats were exposed to 80, 60 or 40% oxygen for 2, 4 or 8 days with or without alpha-tocopherol treatment. The composition of fatty acids in microsomal phospholipids was determined by high-performance liquid chromatography. Microsomal electron transport activity and the levels of lipoperoxides in lung microsomes were determined by measuring the specific activity of NADPH (reduced nicotinamide adenine dinucleotide phosphate)-cytochrome c reductase and by spectrophotometry, respectively. Exposure to 80 or 60% oxygen induced significant decreases in the contents of arachidonic and docosahexaenoic acids, and also reduced microsomal electron transport activity. The level of lipoperoxides was elevated on the 2nd day of exposure to 80 or 60% oxygen, however, it returned to normal thereafter. On the other hand, exposure to 40% oxygen affected none of these parameters. Treatment with alpha-tocopherol prevented the changes in those fatty acids and microsomal function up to 2 days with exposure to 80% oxygen and up to 4 days with exposure to 60% oxygen. However, microsomal dysfunction and reductions of arachidonic and docosahexaenoic acids contents were observed after the 4th day of exposure to 80% oxygen or the 8th day of exposure to 60% oxygen irrespective of alpha-tocopherol administration. On the contrary, alpha-tocopherol administration prevented an elevation of the level of lipoperoxides. These results suggest that lung microsomal dysfunction induced by over 60% oxygen breathing is ascribed to the alteration of fatty acids composition in microsomal phospholipids and that alpha-tocopherol has a protective effect in the early phase.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004579:Electron Transport / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D008054:Lipid Peroxides / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000633:toxicity*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000494:pharmacology*
D005227:Fatty Acids; D008054:Lipid Peroxides; D010743:Phospholipids; D014810:Vitamin E; D010100:Oxygen