In previous studies, we showed that docosahexaenoic acid (DHA) ingestion enhanced the susceptibility of rat liver and kidney to lipid peroxidation, but did not increase lipid peroxide formation to the level expected from the relative peroxidizability index (P-index) of the total tissue lipids. The results suggested the existence of some suppressive mechanisms against DHA-induced tissue lipid peroxide formation, as increased tissue ascorbic acid (AsA) and glutathione levels were observed. Therefore, we focused initially on the role of AsA for the suppressive mechanisms. For this purpose, we examined the influence of different levels of dietary AsA (low, moderate, high and excessive levels were 100, 300 (control), 600 and 3000 mg/kg diet respectively) on the tissue lipid peroxide and antioxidant levels in AsA-requiring Osteogenic Disorder Shionogi/Shi-od/od (ODS) rats fed DHA (6·4 % total energy) for 32 or 33 d. Diets were pair-fed to the DHA- and 100 mg AsA/kg diet-fed group. We found that the lipid peroxide concentrations of liver and kidney in the DHA-fed group receiving 100 mg AsA/kg diet were significantly higher or tended to be higher than those of the DHA-fed groups with AsA at more than the usual control level of 300 mg/kg diet. Contrary to this, the liver α-tocopherol concentration was significantly lower or tended to be lower in the DHA and 100 mg AsA/kg diet-fed group than those of the other DHA-fed groups. However, tissue lipid peroxide formation and α-tocopherol consumption were not suppressed further, even after animals received higher doses of AsA. The present results suggest that higher than normal concentrations of tissue AsA are not necessarily associated with the suppressive mechanisms against dietary DHA-induced tissue lipid peroxide formation.

In a previous study, we found that the extent of dietary n-3 docosahexaenoic acid (DHA)-stimulated tissue lipid peroxidation was less than expected from the relative peroxidizability index of the total tissue lipids in rats with adequate vitamin E nutritional status. This suppression of lipid peroxidation was especially prominent in the liver. To elucidate whether this phenomenon was unique to DHA, we compared the peroxidation effects of n-3 α-linolenic acid (α-LN) and n-3 eicosapentaeonic acid (EPA) with those of DHA in rats. Either α-LN (8·6 % of total energy), EPA (8·2 %), or DHA (8·0 %) and one of two levels of dietary vitamin E (7·5 and 54 mg/kg diet) were fed to rats for 22 d. Levels of conjugated diene, chemiluminescence emission and thiobarbituric acid (TBA)-reactive substance in the liver, kidney, and testis were determined as indicators of lipid peroxidation. In rats fed the DHA diet deficient in vitamin E (7·5 m/g diet), TBA values in the liver, kidney, and testis correlated well with the tissues' relative peroxidizability indices. In rats fed the α-LN diet with an adequate level of vitamin E (54 m/g diet), a close association between relative peroxidizability indices and lipid peroxide levels was observed in all the tissues analysed. However, in rats fed either the EPA diet or the DHA diet with an adequate level of vitamin E, the extent of lipid peroxidation in each tissue was less than expected from the relative peroxidizability index. This suppression was particularly marked in the liver. We concluded that suppression of lipid peroxidation below the relative peroxidizability index was not unique to DHA, but was also seen with EPA, which has five double bonds, in rats with adequate vitamin E nutritional status, but not with α-LN, which has three double bonds.