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

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  • Nasa Yoshihisa
    Department of Pharmacology, Tokyo University of Pharmacy and Life Science
  • Hayashi Michihiko
    Department of Pharmacology, Tokyo University of Pharmacy and Life Science
  • Sasaki Hideo
    Department of Pharmacology, Tokyo University of Pharmacy and Life Science
  • Hayashi Jyun-ichi
    Department of Gerontology, Kyorin University School of Medicine
  • Takeo Satoshi
    Department of Pharmacology, Tokyo University of Pharmacy and Life Science

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  • Long-Term Supplementation With Eicosape

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Abstract

Dietary supplementation of fish oil containing eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-3, DHA) has been shown to exert protective effects on ischemic/reperfused hearts. We determined whether deprivation of fish oil from the diet paradoxically enhances susceptibility of cardiomyocytes to hypoxia/reoxygenation-induced injury and whether supplementation with either EPA or DHA overcomes such alterations. Rats were fed with fish-oil-rich (FOR) diet, fish-oil-deprived (FOD) diet alone, FOD diet with EPA (1 g/kg/day), or FOD diet with DHA (1 g/kg/day) for 4 weeks. The FOD diet reduced n-3 polyunsaturated fatty acids (PUFAs) and increased n-6 PUFAs such as linoleic (C18:2) and arachidonic acids (C20:4) in myocardial phospholipids. EPA or DHA supplementation increased its incorporation into phospholipid pools. Cardiomyocytes isolated by treatment with collagenase were subjected to 150 min of hypoxia and subsequent reoxygenation for 15 min. In the FOD diet group, the number of surviving rod-shaped cells after hypoxia and reoxygenation was smaller than that of the FOR group. Supplementation with EPA did not affect the number of rod-shaped cells, but attenuated reoxygenation-induced reduction in the number of square-shaped cells. In contrast, DHA supplementation did not afford any protection. The results suggest that deprivation of fish oil from dietary intake enhances the susceptibility of cardiomyocytes to hypoxic injury, and EPA, but not DHA, is capable of salvaging cardiomyocytes from hypoxia/reoxygenation-induced damage.

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