The Interactive Effects of N-3 Long-Chain Polyunsaturated Fatty Acids and Methylmercury on the Cardiovascular System

Abstract

Coldwater marine fish, an excellent source of n-3 long chain polyunsaturated fatty acids (LCPUFA), is often contaminated with the environmental pollutant methylmercury (MeHg). N-3 LCPUFA and MeHg have contrasting effects on the cardiovascular system: n-3 LCPUFA decrease blood pressure and the risk of coronary heart disease, and promote an antiarrhythmic effect; MeHg increases blood pressure, causes irregular heart rate and tachycardia. In a previous study we have shown that animals supplemented with n-3 LCPUFA exhibited significantly lower blood pressure compared to n-3 LCPUFA non-supplemented or MeHg exposed groups. It is possible that the opposite effects of dietary n-3 LCPUFA and MeHg on blood pressure can be explained, in part, through changes in the fatty acid profile of cardiac phospholipids and in oxidative status of heart and liver. Adult Long Evans female rats were exposed from 5 to 18 months of age to 0, 0.5, and 5.0 ppm MeHg in drinking water, and fed either a diet with (+) or without (-) n-3 LCPUFA. The fatty acid composition of heart phospholipids was analyzed by gas chromatography. The gene expression of the enzymes of pro-oxidant enzyme (NADPH oxidase) and antioxidant enzymes (catalase, glutathione peroxidase, superoxide dismutase) were determined by RT-PCR. Catalase activity was investigated in liver. Protein oxidation was assessed in heart and liver tissues by measuring protein carbonyl levels. The (+) n-3 LCPUFA diet markedly increased docosahexaenoic acid (DHA) in heart phospholipids as compared to the (-) n-3 LCPUFA diet. Concomitantly, there was a reduction in arachidonic acid (ARA) levels. With a minor exception, there was no effect of mercury exposure on cardiac fatty acid composition. Thus, n-3 LCPUFA significantly improved the fatty acid profiles of the heart, irrespective of mercury concentrations. Dietary n-3 LCPUFA decreased liver and heart gene expression of the pro-oxidant enzyme (NADPH oxidase) (P = 0.001), whereas MeHg increased the expression of this enzyme (P = 0.01) only in the liver. Animals not exposed to MeHg and supplemented with n-3 LCPUFA demonstrated the greatest gene expression of antioxidant enzymes (glutathione peroxidase and catalase). No significant differences were observed in the gene expression of superoxide dismutase in either liver or heart, and in the hepatic catalase activity. In n-3 LCPUFA-fed animals, in the absence of MeHg exposure, cardiac protein oxidation was decreased by 37% compared to the (-) n-3 LCPUFA group. The n-3 LCPUFA incorporation into cardiac phospholipids and their beneficial effect on oxidative status may explain in part the beneficial effects of fish consumption on blood pressure and cardiovascular disease. Therefore, a balance between the risks and benefits of fish intake can be obtained by consumption of fish low in MeHg but rich in n-3 LCPUFA.