Abstract
Reactive oxygen species paradoxically underpin both ischaemia/reperfusion (I/R) damage and ischaemic preconditioning (IPC) cardioprotection. Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) are highly susceptible to peroxidation, but are paradoxically cardioprotective. This study tested the hypothesis that LCn-3 PUFA cardioprotection is underpinned by peroxidation, upregulating antioxidant activity to reduce I/R-induced lipid oxidation, and the mechanisms of this nutritional preconditioning contrast to mechanisms of IPC. Rats were fed: fish oil (LCn-3 PUFA); sunflower seed oil (n-6 PUFA); or beef tallow (saturated fat, SF) enriched diets for six weeks. Isolated hearts were subject to: 180 min normoxic perfusion; a 30 min coronary occlusion ischaemia protocol then 120 min normoxic reperfusion; or a 3 × 5 min global IPC protocol, 30 min ischaemia, then reperfusion. Dietary LCn-3 PUFA raised basal: membrane docosahexaenoic acid (22:6n-3 DHA); fatty acid peroxidisability index; concentrations of lipid oxidation products; and superoxide dismutase (MnSOD) activity (but not CuZnSOD or glutathione peroxidase). Infarct size correlated inversely with basal MnSOD activity (r2 = 0.85) in the ischaemia protocol and positively with I/R-induced lipid oxidation (lipid hydroperoxides (LPO), r2 = 0.475; malondialdehyde (MDA), r2 = 0.583) across ischaemia and IPC protocols. While both dietary fish oil and IPC infarct-reduction were associated with reduced I/R-induced lipid oxidation, fish oil produced nutritional preconditioning by prior LCn-3 PUFA incorporation and increased peroxidisability leading to up-regulated mitochondrial SOD antioxidant activity.
Highlights
Regular consumption of fish or fish oil reduces cardiovascular mortality [1], often without modifying classical risk factors
Ischaemic preconditioning (IPC) protocol (n = 6 per diet): Hearts were subjected to three cycles of five minutes global ischaemia, each followed by five minutes normoxic reperfusion, prior to the 30 min index-ischaemia 120 min normoxic reperfusion [5]
Data were analysed by two-way analysis of variance (ANOVA) for diet and treatment main effects and by multi-way ANOVA for diet, treatment and ISCH versus non-I tissue main effects
Summary
Regular consumption of fish or fish oil reduces cardiovascular mortality [1], often without modifying classical risk factors. Myocardial ischaemia and reperfusion (I/R) stimulates production of reactive oxygen species (ROS) and depletes antioxidants in the heart, creating oxidative stress, oxidation of biomolecules and cell damage These free radicals act as triggers of IPC [15,16]. The current study tested the hypothesis that incorporation of LCn-3 PUFA into myocardial membranes increases their peroxidation potential and basal fatty acid oxidation, which by their constant presence, in turn increases endogenous antioxidant enzymes to confer physiological cardioprotective actions against I/R-stimulated oxidative stress. We propose that this will contrast to the mechanism of early IPC cardioprotection
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