Enhanced level of n-3 fatty acid in membrane phospholipids induces lipid peroxidation in rats fed dietary docosahexaenoic acid oil

Atherosclerosis. 2001 Mar;155(1):9-18. doi: 10.1016/s0021-9150(00)00523-2.


The effect of dietary docosahexaenoic acid (DHA, 22:6n-3) oil with different lipid types on lipid peroxidation was studied in rats. Each group of male Sprague-Dawley rats was pair fed 15% (w/w) of either DHA-triglycerides (DHA-TG), DHA-ethyl esters (DHA-EE) or DHA-phospholipids (DHA-PL) for up to 3 weeks. The palm oil (supplemented with 20% soybean oil) diet without DHA was fed as the control. Dietary DHA oils lowered plasma triglyceride concentrations in rats fed DHA-TG (by 30%), DHA-EE (by 45%) and DHA-PL (by 27%), compared to control. The incorporation of dietary DHA into plasma and liver phospholipids was more pronounced in the DHA-TG and DHA-EE group than in the DHA-PL group. However, DHA oil intake negatively influenced lipid peroxidation in both plasma and liver. Phospholipid peroxidation in plasma and liver was significantly higher than control in rats fed DHA-TG or DHA-EE, but not DHA-PL. These results are consistent with increased thiobarbituric acid reactive substances (TBARS) and decreased alpha-tocopherol levels in plasma and liver. In addition, liver microsomes from rats of each group were exposed to a mixture of chelated iron (Fe(3+)/ADP) and NADPH to determine the rate of peroxidative damage. During NADPH-dependent peroxidation of microsomes, the accumulation of phospholipid hydroperoxides, as well as TBARS, were elevated and alpha-tocopherol levels were significantly exhausted in DHA-TG and DHA-EE groups. During microsomal lipid peroxidation, there was a greater loss of n-3 fatty acids (mainly DHA) than of n-6 fatty acids, including arachidonic acid (20:4n-6). These results indicate that polyunsaturation of n-3 fatty acids is the most important target for lipid peroxidation. This suggests that the ingestion of large amounts of DHA oil enhances lipid peroxidation in the target membranes where greater amounts of n-3 fatty acids are incorporated, thereby increasing the peroxidizability and possibly accelerating the atherosclerotic process.

MeSH terms

  • Animals
  • Dietary Fats, Unsaturated / administration & dosage*
  • Docosahexaenoic Acids / administration & dosage*
  • Docosahexaenoic Acids / metabolism
  • Fatty Acids / analysis*
  • Fatty Acids, Omega-3 / analysis*
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated / analysis
  • Lipid Peroxidation* / drug effects
  • Lipids / analysis
  • Lipids / blood
  • Liver / chemistry
  • Liver / metabolism
  • Male
  • Membrane Lipids / chemistry*
  • Microsomes, Liver / metabolism*
  • NADP / pharmacology
  • Oxidative Stress
  • Phospholipids / administration & dosage
  • Phospholipids / analysis
  • Phospholipids / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Thiobarbituric Acid Reactive Substances / analysis
  • Triglycerides / administration & dosage
  • Triglycerides / blood
  • Vitamin E / analysis
  • Vitamin E / blood


  • Dietary Fats, Unsaturated
  • Fatty Acids
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated
  • Lipids
  • Membrane Lipids
  • Phospholipids
  • Thiobarbituric Acid Reactive Substances
  • Triglycerides
  • Vitamin E
  • Docosahexaenoic Acids
  • NADP
  • 4,7,10,13,16,19-docosahexaenoic acid ethyl ester