title: Up-Regulation of Mitochondrial Antioxidant Superoxide Dismutase Underpins Persistent Cardiac Nutritional-Preconditioning by Long Chain n-3 Polyunsaturated Fatty Acids in the Rat.
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.
authors.affiliation: Division of Medical and Exercise Science, School of Medicine, Faculty of Science Medicine and Health, University of Wollongong, Wollongong NSW 2522, Australia. Grace.Abdukeyum@hnehealth.nsw.gov.au.
authors.forename: Grace G
authors.initials: GG
authors.lastname: Abdukeyum
authors.affiliation: Centre of Cardiovascular Research &amp; Education in Therapeutics, School of Public Health &amp; Preventive Medicine, Monash University, Melbourne VIC 3004, Australia. alice.owen@monash.edu.
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Owen
authors.affiliation: Centre for Human and Applied Physiology, Graduate School of Medicine, School of Medicine, Faculty of Science Medicine and Health, University of Wollongong, Wollongong NSW 2522, Australia. tlarkin@uow.edu.au.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Larkin
authors.affiliation: Centre for Human and Applied Physiology, Graduate School of Medicine, School of Medicine, Faculty of Science Medicine and Health, University of Wollongong, Wollongong NSW 2522, Australia. petermcl@uow.edu.au.
authors.forename: Peter L
authors.initials: PL
authors.lastname: McLennan
keywords: antioxidant; fish oil; infarct; ischaemia; lipid oxidation; n-3 PUFA; preconditioning; reactive oxygen species; reperfusion