|Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
In previous studies, we showed that docosahexaenoic acid (DHA) ingestion enhance 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-stimulated tissue lipid peroxide formation, as observed increased tissue ascorbic acid (AsA) and glutathione (GSH) levels. Furthermore, we have proposed that incorporation of docosahexaenoic acid (DHA) into phosphatidylethanolamine (PE) might enhance resistance to lipid peroxidation in vivo.
In this study, therefore, we focused initially on the roles of AsA and/or GSH for the suppressive mechanisms and secondly on the relationship between the transbilayer distribution of PE and oxidative stability of DHA combined with PE.
We examined the influences of different levels of dietary AsA and methionine, the latter of which is r
equired for GSH-synthesis, on the liver lipid peroxide and antioxidant levels in vitamin C-requiring ODS rats. We found that physiological levels of AsA and methionine were required for suppressing DHA-stimulated lipid peroxide formation and consumption of vitamin E, but the dietary AsA and methionine over physiological levels did not suppress further the formation and consumption. In addition, when rats ingested a low level of methionine, liver lipid peroxide formation and glutathione-S-transferase activity were increased. These results suggested a limited antioxidant ability potentiated by AsA and GSH. Therefore, other factor such as detoxification of lipid peroxides by glutathione-S-transferase, may be related to the suppressive mechanisms.
In addition, to modulate the transbilayer distribution of PE (PE-DHA) obtained from the liver of rats fed DHA, we used phosphatidylcholine (PC) with two types of acyl chain moiety: dipalmitoyl (PC 16 : 0) and dioleoyl (PC 18 : 1). The proportion of PE-DHA in the liposomal external layer was significantly higher in liposomes containing PC18 : 1 than in those containing PC16 : 0. This tendency was more pronounced in liposomes extruded using a polycarbonate filter with smaller pore sizes. Additionally, PE-DHA in the external layer of liposomes prepared using a filter with smaller pore sizes could protect DHA itself from 2, 2' -azobis (2-amino-propane) dihydrochloride -mediated lipid peroxidation. Less