Dietary Supplementation with Docosahexanoic Acid or Arachidonic Acid Delay Ca2+ ‐Induced Permeability Transition Pore Opening in Cardiac Mitochondria

Abstract

Supplementation with docosahexanoic acid (DHA, commonly found in fish oil) in clinically relevant amounts causes a 2-fold increase in DHA in cardiac phospholipids, and delays Ca2+-induced mitochondrial permeability transition pore (MPTP) opening. The mechanism for this effect is not clear, however the increase in DHA is accompanied by a decrease in the ù-6 PUFA arachidonic acid (ARA), which could be responsible for the effects on the MPTP. We determined the role of ARA on MPTP opening by feeding rats DHA, ARA or DHA+ARA. Male Wistar rats were fed either a los DHA+AHA diet(CTRL), a diet containing DHA or ARA at 2.5% of energy intake, or both DHA and ARA at 2.5% each, for 10 wks. Cardiac mitochondria were isolated. All three diets profoundly altered the phospholipid composition of mitochondria compared to CTRL. Both the DHA and ARA groups delayed Ca2+-induced MPTP opening vs. CTRL (p<0.05) while DHA+ARA increased sensitivity to MPTP opening (p<0.05 vs CTRL, DHA or ARA). Furthermore, both diets containing ARA significantly increased the pro-inflammatory marker TBX B2 by 2- to 3-fold compared to CTRL and DHA diets (p<0.05). DHA+ARA also increased lipid peroxidation compared to ARA alone (p=0.008) and to CTRL (p=0.034). This suggests that the effect of DHA on MPTP is not due to depletion of ARA. DHA+ARA showed no added benefit, but rather sensitized MPTP to opening, suggesting that a very large dose of PUFA might be detrimental.