Decreased turnovers of glutathione and ascorbic acid in watanabe heritablehyperlipidemic rabbits

Oxidative stress has been postulated to play important roles in the pathoge nesis of various diseases such as atherosclerosis in hyperlipidemic subject s. Although the possible role of oxidation of low-density lipoprotein (LDL) in the etiology of atherosclerosis has been studied extensively, the turno ver of endogenous antioxidants, which is an important protection system aga inst oxidative stress, remains to be elucidated. The aim of our study was t o determine the change of the turnover of endogenous antioxidants such as g lutathione and ascorbic acid in case of hyperlipidemia, using Japanese whit e rabbits (JW) and Watanabe heritable hyperlipidemic rabbits (WHHL). The le vels of total glutathione and low molecular weight thiols in the liver, kid ney, and other organs in both strains of rabbits were similar. However, a k inetic analysis using L-buthionine-(S,R)-sulfoximine revealed that the rate of glutathione turnover in the liver and kidney of WHHL was about 50% lowe r than that of JW. Furthermore, intravenously administered ascorbic acid di sappeared more slowly in WHHL, than in JW. These results indicate that the turnovers of both glutathione and ascorbic acid in WHHL, are depressed in c omparison with that in Tmi. These changes would he closely related to the i ncreased oxidizability of lipids in the circulation of hyperlipidemic subje cts.