Dietary n-3 polyunsaturated fatty acids increase oxidative stress in rats with intracerebral hemorrhagic stroke

Intake of n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been suggested to associate with an increased risk of hemorrhagic stroke. The present study was designed to investigate the hypothesis that EPA and DHA increase oxidative stress and hemorrhage volume in rats with intracerebral hemorrhagic (ICH) stroke. Thirty-five-week-old male rats were fed an American Institute of Nutrition–93M diet containing 0% (n = 27), 0.5% (n = 15), or 1% EPA + DHA of total energy for 5 weeks. Of 5 rats fed 1% EPA + DHA (41%), 5 died because of excessive bleeding within 12 hours after ICH surgery. Behavior test score and hemorrhage volume were significantly (P < .05) greater in the 1% EPA + DHA–fed rats than in other rats. Magnetic resonance imaging consistently showed that edema and bleeding were visible in only the rats fed 1% EPA + DHA. Levels of superoxide dismutase and glutathione were significantly (P < .05) lower in rats fed 0.5% and 1% EPA + DHA than those fed 0% EPA + DHA. Thiobarbituric acid–reactive substance content was significantly (P < .05) higher in 1% EPA + DHA–fed rats than in 0% and 0.5% EPA + DHA–fed rats. The level of 8-hydroxydeoxyguanosine was significantly (P < .05) higher in ICH rats with all diets than in sham surgery rats. Brain levels of EPA and DHA were highest in rats fed 1% EPA + DHA than in rats fed 0% and 0.5% EPA + DHA. These results suggested that intake of 1% EPA + DHA of total energy could lead to oxidative damage to the brain and thus increase the risk of intracerebral hemorrhagic stroke in this rat model.