Dietary modulation of fatty acid profiles and oxidative status of rat hepatocyte nodules: effect of different n-6/n-3 fatty acid ratios.

Male Fischer rats were fed the AIN 76A diet containing varying n-6/n-3 FA ratios using sunflower oil (SFO), soybean oil (SOY), and SFO supplemented with EPA-50 and GLA-80 (GLA) as fat sources. Hepatocyte nodules, induced using diethylnitrosamine followed by 2-acetylaminofluorene/partial hepatectomy promotion, were harvested, with surrounding and respective dietary control tissues, 3 mon after partial hepatectomy. The altered growth pattern of hepatocyte nodules in rats fed SFO is associated with a distinct lipid pattern entailing an increased concentration of PE, resulting in increased levels of 20:4n-6. In addition, there is an accumulation of 18:1 n-9 and 18:2n-6 and a decrease in the end products of the n-3 metabolic pathway in PC, suggesting a dysfunctional delta-6-desaturase enzyme. The hepatocyte nodules of the SFO-fed rats exhibited a significantly reduced lipid peroxidation level that was associated with an increase in the glutathione (GSH) concentration. The low n-6/n-3 FA ratio diets significantly decreased 20:4n-6 in PC and PE phospholipid fractions with a concomitant increase in 20:5n-3, 22:5n-3, and 22:6n-3. The resultant changes in the 20:4/20:5 FA ratio and the 20:3n-6 FA level in the case of the GLA diet suggest a reduction of prostaglandin synthesis of the 2-series. The GLA diet also counteracted the increased level of 20:4n-6 in PE by equalizing the nodule/surrounding ratio. The low n-6/n-3 ratio diets significantly increased lipid peroxidation levels in hepatocyte nodules, mimicking the level in the surrounding and control tissue while GSH was decreased. An increase in n-3 FA levels and oxidative status resulted in a reduction in the number of glutathione-S-transferase positive foci in the liver of the GLA-fed rats. Modulation of cancer development with low n-6/n-3 ratio diets containing specific dietary FA could be a promising tool in cancer intervention in the liver.