Up-Regulation of Mitochondrial Antioxidant Superoxide Dismutase Underpins Persistent Cardiac Nutritional-Preconditioning by Long Chain n-3 Polyunsaturated Fatty Acids in the Rat
1
Division of Medical and Exercise Science, School of Medicine, Faculty of Science Medicine and Health, University of Wollongong, Wollongong NSW 2522, Australia
2
Centre of Cardiovascular Research & Education in Therapeutics, School of Public Health & Preventive Medicine, Monash University, Melbourne VIC 3004, Australia
3
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
*
Author to whom correspondence should be addressed.
Academic Editors: Lindsay Brown, Bernhard Rauch and Hemant Poudyal
J. Clin. Med. 2016, 5(3), 32; https://doi.org/10.3390/jcm5030032
Received: 16 November 2015 / Revised: 26 February 2016 / Accepted: 29 February 2016 / Published: 4 March 2016
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease)
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.
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Keywords:
fish oil; preconditioning; antioxidant; reactive oxygen species; ischaemia; reperfusion; n-3 PUFA; lipid oxidation; infarct
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Abdukeyum, G.G.; Owen, A.J.; Larkin, T.A.; McLennan, P.L. Up-Regulation of Mitochondrial Antioxidant Superoxide Dismutase Underpins Persistent Cardiac Nutritional-Preconditioning by Long Chain n-3 Polyunsaturated Fatty Acids in the Rat. J. Clin. Med. 2016, 5, 32.
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