Abstract
Myocardial infarction (MI) is an irreversible event caused by cardiac ischemia and may be fatal. Studies reported that increased intake of n-3 polyunsaturated fatty acids (PUFA) namely, eicosapentaenoic acid and docosahexaenoic acid reduce the risk of cardiovascular disease and lower the incidence of MI. Nonetheless, the cardioprotective effect of plant n-3-PUFA such as α-linolenic acid (ALA) in the diet is not conclusive. In this study, Sprague Dawley rats were supplemented with isocaloric diets enriched with ALA rich flaxseed (FS) and flaxseed oil (FSO), and normal chow (Control) for 4 weeks. MI was induced by isoproterenol (ISO) injection. Results showed that all ALA-enriched diets displayed cardioprotection against MI. The heart to body weight ratio, plasma LDH activity and plasma cTnI were reduced compared to ISO and was prominent in FS diet. ALA and EPA were up-regulated in both tissues and plasma by ALA-diets compared to Control and remained higher than ISO groups. Notably, LOX-mediated HETEs decreased whereas LOX-mediated HDHAs were elevated in both tissues and plasma of ALA-enriched diets compared to ISO. In addition, non-enzymatic oxidized products from arachidonic acid including 15-F2t-IsoP were reduced in both tissues and plasma of MI rats supplemented with ALA-enriched diets while those from n-3 PUFAs including F4-NeuroPs, PhytoPs and PhytoFs were elevated compared to control. ALA-enriched diets particularly flaxseed reduced gene expressions of inflammatory cytokines namely IL-1β, IL-6 and TNFα and prevented the down regulation of antioxidant catalase in the heart tissues. In conclusion ALA-enriched diets potentially exerted cardioprotection through the regulation of anti-inflammatory and anti-oxidative mediators from n-3 PUFA autooxidation.
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Key Points
In this study, cardioprotective effect of ALA was investigated in rodents. Sprague Dawley rats were fed with normal chow diet and ALA-diets supplemented by either flaxseed (FS) or flaxseed oil (FSO). Both are known to be rich in ALA but FSO lacks dietary fiber, lignans and proteins, and some antioxidant phenolic compounds since they are removed in the defatted flaxseed meal as ‘by-product’ during extraction. Myocardial infarction (MI) was induced by using isoproterenol (ISO).
Excessive amount of ISO causes increased heart rate, subendocardial myocardial ischemia, hypoxia, cardiomyocyte necrosis and develop infarct-like lesions in the rat heart tissues which are similar to pathophysiology of human MI. The physiological changes triggered by ISO in the rat heart is due to excessive production of free radicals from oxidative metabolism by catecholamines. The study showed that the ratio increased significantly in ISO-induced MI rats by 33% compared to healthy control rats, indicating that cardiac hypertrophy took place. Indeed, marked reduction of the ratio with ALA-diets especially FS, suggest the diet to be anti-hypertrophic and able to protect the heart against stress. The cardioprotective effect of ALA-diets were further demonstrated by plasma cTnI level and LDH activity. Plasma cTn (I or T) is the most preferred biomarker for cardiac necrosis due to its high sensitivity and specificity while LDH is the first diagnostic enzyme for myocardial infarction [34]. It was found that LDH are released to the extracellular fluid in myocardial injury. Altogether, in this study n-3 PUFA (ALA) from plant-based diets provided cardiac protection as like those (EPA and DHA) from marine-based diets. For the first time, we also displayed the mediation of oxidized PUFA products by ALA-diet, notably 4-F4t-NeuroP and HDHA derived from DHA. Furthermore, PhytoPs and PhytoFs appeared to have potential regulatory role in cardiac function. However, it is also noted, plant-based food rich in n-3 PUFA like flaxseed contain high levels of functional phenolic compounds which may have added to the cardioprotective effect.