Long-Term Supplementation With Eicosapentaenoic Acid Salvages Cardiomyocytes From Hypoxia/Reoxygenation-Induced Injury in Rats Fed With Fish-Oil-Deprived Diet

Nasa, Yoshihisa; Hayashi, Michihiko; Sasaki, Hideo; Hayashi, Jyun-ichi; Takeo, Satoshi

doi:10.1254/jjp.77.137

Cited by 10 publications

(6 citation statements)

References 41 publications

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“…Also, the FFA profile in heart extracts of lean and obese mice largely reflected the FA composition of the diet. In particular, levels of arachidonic acid (n‐6), a proinflammatory FA, were significantly higher, whereas levels of DHA, which is known to exert cardioprotective effects (27), were lower in heart extracts of obese mice. Palmitic acid levels, a saturated FA that induces apoptosis in cardiomyocytes (28), were approximately sevenfold higher in cardiac extracts of obese mice compared with lean mice.…”

Section: Discussionmentioning

confidence: 99%

Increased Myocardial Susceptibility to Repetitive Ischemia With High‐fat diet‐induced Obesit

Thakker

Frangogiannis

Zymek

et al. 2008

Obesity

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Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dysregulation of these adaptive responses in diet‐induced obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J mice were subjected to 15 min of daily repetitive I/R while under short‐acting anesthesia, a protocol that results in the development of fibrotic cardiomyopathy. Cardiac lipids and candidate gene expression were analyzed at 3 days, and histology at 5 days of repetitive I/R. Total free fatty acids (FFAs) in the cardiac extracts of DIO mice were significantly elevated, reflecting primarily the dietary fatty acid (FA) composition. Compared with lean controls, cardiac FA oxidation (FAO) capacity of DIO mice was significantly higher, concurrent with increased expression of FA metabolism gene transcripts. Following 15 min of daily repetitive I/R for 3 or 5 days, DIO mice exhibited increased susceptibility to I/R and, in contrast to lean mice, developed microinfarction, which was associated with an exaggerated inflammatory response. Repetitive I/R in DIO mice was associated with more profound significant downregulation of FA metabolism gene transcripts and elevated FFAs and triglycerides. Maladaptive metabolic changes of FA metabolism contribute to enhanced myocardial injury in diet‐induced obesity.

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Section: Discussionmentioning

confidence: 99%

Increased Myocardial Susceptibility to Repetitive Ischemia With High‐fat diet‐induced Obesit

Thakker

Frangogiannis

Zymek

et al. 2008

Obesity

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“…These results suggest that the n-3 PUFA deficient diet may increase the severity of cellular damage after zero-flow ischemia in isolated perfused rat hearts. In this respect, Nasa et al have shown that deprivation of fish oil from the diet enhances the susceptibility of cardiomyocytes to hypoxic injury (20). The mechanisms by which the n-3 PUFA deficient diet could increase the severity of myocardial ischemia are not clear.…”

Section: Discussionmentioning

confidence: 99%

Acute in vivo administration of a fish oil-containing emulsion improves post-ischemic cardiac function in n-3-depleted rats

Peltier

Malaisse²,

Portois³

et al. 2006

Int J Mol Med

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Abstract.A novel i.v. lipid preparation (MCT:FO) containing 80% medium chain-triacylglycerols and 20% fish oil was recently developed to rapidly replenish cell membrane phospholipids with omega 3 (n-3) polyunsaturated fatty acids (PUFA). In regard of this property, we investigated the effect of a single i.v. administration of MCT:FO on the recovery of cardiac function after ischemia in control and n-3-depleted rats. Results were compared with those obtained either with a control preparation, where FO was replaced by triolein (MCT:OO), or with saline. Saline (1 ml) or lipid preparation (also 1 ml) was injected as a bolus via the left saphenous vein. After 60 min the heart was removed and perfused for 20 min in normoxic conditions according to Langendorff. Thereafter, the heart was subjected to a 20 min zero-flow normothermic ischemia, followed by 40 min reperfusion. Cardiac mechanical and metabolic functions were monitored. In control rats, the previous administration of a lipid preparation (MCT:FO or MCT:OO) versus saline improved cardiac function during aerobic reperfusion post-ischemia. N-3-depleted rats showed decreased basal cardiac function and impaired recovery following ischemia. However, the bolus injection of MCT:FO opposed the deleterious effect of longterm n-3-deficiency and, in this respect, was superior to MCT:OO over the first 20 min of reperfusion. This novel approach to rapidly correct n-3 PUFA-deficiency might be clinically relevant and offer interesting perspectives in the management of acute ischemic accidents.

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“…Although some studies were inconclusive [162 -164], the vast majority reported a beneficial effect of either marine or plant n-3 PUFAs. Long-term dietary enrichment with n-3 PUFAs reduced infarct size [165 -167], improved the recovery of mechanical cardiac activity during the reestablishment of coronary flow [90, 91, 168 -173], prevented the release of creatine kinase or lactate dehydrogenase [90, 91, 169 -171, 174, 175], favoured the recovery of action potential during reoxygenation [176,177] and improved cell survival during hypoxia [178,179]. These studies thus clearly indicated that n-3 PUFAs reduce the cellular damage triggered by ischemia and reperfusion.…”

Section: Cell Damage During Ischemia and Reperfusionmentioning

confidence: 99%

“…Exogenous DHA may even be deleterious during ischemia and reperfusion [181]. The majority of studies agreed that EPA is responsible for the beneficial effects of n-3 PUFAs when compared with DHA [91, 179,181,182], although some investigations also showed a protective effect of DHA [178,183]. The higher the level of EPA in cardiac phospholipids, the greater the protection during ischemia and reperfusion [91].…”

Section: Cell Damage During Ischemia and Reperfusionmentioning

confidence: 99%

Dietary n-3 polyunsaturated fatty acids and coronary heart disease-related mortality: a possible mechanism of action

Demaison¹,

Moreau²

2002

Cellular and Molecular Life Sciences (CMLS)

106

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Epidemiological and interventional studies indicate that dietary n-3 PUFA reduces mortality due to coronary heart disease (CHD). They act at a low dose, since one or two meals with fatty fish per week is sufficient to provide protection when compared with no fish intake. These fatty acids are effective in providing primary prevention in low- and high-risk subjects and secondary prevention. At high doses, dietary n-3 PUFAs have several beneficial properties. First, they act favourably on blood characteristics: they are hypocholesterolemic and hypotriglyceridemic; they reduce platelet aggregation; they exhibit antithrombotic and fibrinolytic activities; they reduce blood viscosity and they exhibit antiinflammatory action. Second, they reduce ischemia/reperfusion-induced cellular damage. This effect is apparently due to the incorporation of eicosapentaenoic acid in membrane phospholipids. Third, they reduce ischemia and reperfusion arrhythmias. All the effects exerted by n-3 PUFAs at high doses are incompatible with the beneficial action on CHD mortality in humans observed at low doses, where their main properties are related to circulation in the form of free fatty acids. Numerous experimental studies have indicated that low concentrations of exogenous n-3 PUFAs reduce the severity of cardiac arrhythmias. This effect is probably responsible for the protective action of n-3 PUFA on CHD mortality. Further studies are necessary to confirm this assumption in animals. Such studies should take account of the fact that only a low dose of n-3 PUFA (20 mg/kg/day) is necessary to afford protection. Furthermore, since the beneficial effect of n-3 PUFAs on CHD mortality is observed in fish eaters versus no-fish eaters, and since populations in industrialised countries consume excess n-6 PUFAs, control animals in long-term dietary experiments should be fed a diet with only n-6 fatty acids as a source of PUFAs.

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Long-Term Supplementation With Eicosapentaenoic Acid Salvages Cardiomyocytes From Hypoxia/Reoxygenation-Induced Injury in Rats Fed With Fish-Oil-Deprived Diet

Cited by 10 publications

References 41 publications

Increased Myocardial Susceptibility to Repetitive Ischemia With High‐fat diet‐induced Obesit

Increased Myocardial Susceptibility to Repetitive Ischemia With High‐fat diet‐induced Obesit

Acute in vivo administration of a fish oil-containing emulsion improves post-ischemic cardiac function in n-3-depleted rats

Dietary n-3 polyunsaturated fatty acids and coronary heart disease-related mortality: a possible mechanism of action

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