Importance of the polyunsaturated fatty acid to vitamin E ratio in the resistance of rat lung microsomes to lipid peroxidation

Rat lung microsomes and liposomes made from isolated lung microsomal lipids were found to be much more resistant to lipid peroxidation than those from liver in both enzymatic and nonenzymatic systems. The polyunsaturated fatty acid (PUFA) content of isolated lung microsomal lipids was 28% of total fatty acids, while liver was 54%. The vitamin E (α-tocopherol) content of isolated lung microsomal lipids was 2.13 nmol/μmol lipid phosphate and that of liver was 0.43. Individually, neither the lower PUFA content nor higher vitamin E levels could account for the resistance of lung microsomal lipids to peroxidation. Distearoyl-L-a-phosphatidylcholine and/or α-tocopherol were added to liver microsomal lipids to achieve different PUFA to vitamin E ratios at PUFA contents of 28% or 54%, and the resulting liposomes were subjected to an NADPH-dependent lipid peroxidation system utilizing cytochrome P450 reductase, EDTA-Fe⁺³, and ADP-Fe⁺³. Liposomes having PUFA to vitamin E ratios less than approximately 250 nmol PUFA/nmol vitamin E were resistant to peroxidation, whereas lipid peroxidation, as evidenced by malondialdehyde production, occurred in liposomes having higher ratios. When lipid peroxidation occurred, 40%–60% of the liposomal vitamin E was irreversibly oxidized. Irreversible oxidation did not occur in the absence of lipid peroxidation. These studies indicated that the low PUFA to vitamin E ratio in lung microsomes and isolated microsomal lipids was sufficient to account for the observed resistance to lipid peroxidation.