Fish oil increases antioxidant enzyme activities in macrophages and reduces atherosclerotic lesions in apoE-knockout mice.

OBJECTIVES The molecular and cellular mechanisms that fish oil (FO) exerts its physiological function are complicated. The present study brings evidence on the in vivo effect of FO on the development of atherosclerosis in apolipoprotein E knockout (apoE(-/-)) mice. We also test the hypothesis that the modulation of the cellular oxidative stress and antioxidant status contributes to the anti-atherosclerotic effect of FO. METHODS AND RESULTS ApoE(-/-) mice were fed a diet rich either in FO or corn oil (CO) for 10 weeks. Both FO and CO had a plasma triacylglycerol-raising effect in apoE(-/-) mice, whereas aortic atherosclerotic lesions were significantly reduced in the mice that had consumed a high FO diet compared to those fed a high CO diet. The levels of hepatic superoxide dismutase (SOD) and catalase (CAT) activities were remarkably higher in the mice fed the FO diet than in mice fed the CO diet and the control diet. We then investigated the effects of FO and CO on the production of superoxide anion (O2*-)) and reactive oxygen species (ROS) in cultured J774 macrophages. Antioxidant status was assessed by the determination of antioxidant enzyme activities. Both FO and CO induced high levels of O2*-) and total ROS at a short time in macrophages. However, only the FO group restored the induction of O2*-) and ROS to near basal levels after oil treatment for 24 h. Throughout the time course experiments, antioxidant enzyme activities in the FO group mostly displayed a greater increase than in the corresponding CO group after the same time period of oil treatment. CONCLUSIONS In the present study, FO reduced the formation of atherosclerotic lesions in the aortic arteries of apoE(-/-) mice not through any lipid-lowering effect. The protective role of FO in the development of atherosclerosis may result from its antioxidative defense mechanism through the induction of antioxidant enzyme activities.