Omega-3 reduces oxidative stress-induced DNA damage

  • expertomega3
  • 03/02/2018

The role of DNA damage in atherogenesis is the focus of considerable interest. It was first identified in patients with progeroid syndromes (such as Werner’s syndrome in adults, caused by mutations in genes that encoded for DNA repair protein, or Hutchinson-Gilford syndrome in children, in which damage in DNA builds up as a result of defects in the nucleus), which presents with early-onset atherosclerosis. This suggested a relationship between atherosclerosis and DNA damage , which was later confirmed with evidence of the involvement of such DNA damage in the development by atherosclerotic plaques.

Reactive oxygen species (ROS) are the most frequent cause of DNA damage. Thus reducing ROS-induced DNA damage could be crucial in preventing atherosclerosis and associated cardiovascular disease (CVD). ROSs are constantly produced by sub-products of cellular or normal metabolism or in response to certain stimuli (such as ionizing radiation or chemicals) and can cause a variety of lesions to DNA (chemical modification or loss of bases, formation of crossed or broken, single or double chain links). Cells produce antioxidant molecules to defend against ROSs.

Data from in vitro studies carried out by researchers from Hiroshima University and the Fukushima Medical University (Japan) indicate that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) could favour an antioxidant response in human aortic endothelial cells (exposure to EPA and DHA increases mRNA levels of antioxidant molecules) and reduce ROSs, thereby protecting the DNA from the harmful effects of the ROSs (and, consequently, the cell damage they cause).

Persistent damage to DNA produces senescence, apoptosis and inflammation. Previously, EPA had been observed to have protective effects on hydrogen peroxide (H2O2)-induced cellular death. A study performed by Japanese researchers shows that omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate oxidative stress-induced inflammatory gene expression and senescence. Bearing this in mind, n-3 PUFAs could prevent progression of the plaque and favour its stability, partly by reducing DNA damage and subsequent cellular senescence.

Since the correlation between high n-3 PUFA consumption and low incidence of CVD was revealed in the 1970s, numerous studies have been published that support the anti-atherogenic, anti-thrombotic and blood pressure-reducing effects of these acids, as well as their plasma triglyceride-reducing, anti-inflammatory and endothelial function-improving effects. However, the mechanisms by which n-3 PUFAs exert these effects are still not completely known, although their anti-inflammatory mechanisms are now clearer (with the discovery of pro-resolving lipid mediators and the fact that the G-protein-coupled receptor 120 is n-3 PUFA-specific). However, the mechanisms by which n-3 PUFAs modulate endothelial function have still not been fully explained.

The findings in this study indicate that the genome protective effects of n-3 PUFAs are mediated by reducing DNA damage (due to ROSs in this study) rather than by promoting DNA repair systems. Reducing DNA damage could be a possible mechanism by which n-3 PUFAs exert their cardioprotective effects, suggesting they could be possible therapeutic agents for CVD.

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