Yoshihisa Nasa (1), Michihiko Hayashi (1), Hideo Sasaki (1), Jyun-ichi
Hayashi (2) and Satoshi Takeo (1)
(1) Department of Pharmacology, Tokyo University of Pharmacy and Life
Science, Horinouchi 1432-1, Hachioji, Tokyo 192-0392, Japan
(2) Department of Gerontology, Kyorin University School of Medicine, Shinkawa
6-20-2, Mitaka, Tokyo 181-0004, Japan
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.
Keywords: Fish oil, Eicosapentaenoic acid (EPA), Docosahexaenoic acid
(DHA), Hypoxia/reoxygenation, Cardiomyocyte