Premium
Age‐associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes—reversal with ( R )‐α‐lipoic acid supplementation
Author(s) -
Lykkesfeldt Jens,
Hagen Tory M.,
Vinarsky Vladimir,
Ames Bruce N.
Publication year - 1998
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.12.12.1183
Subject(s) - ascorbic acid , oxidative stress , lipoic acid , dehydroascorbic acid , antioxidant , medicine , chemistry , endocrinology , biochemistry , biosynthesis , biology , food science , enzyme
Ascorbic acid recycling from dehydroascorbic acid and biosynthesis from gulono‐1,4‐lactone were used as measures of cellular response capacity to increased oxidative stress induced by tert ‐butylhydroperoxide. The hepatic ascorbic acid concentration was 54% lower in cells from old rats when compared to cells isolated from young rats ( P < 0.0005). Freshly isolated hepatocytes from old rats exhibited a significantly decreased ascorbic acid recycling capacity in response to oxidative stress ( P < 0.005) compared to cells from young rats. Ascorbic acid synthesis in these cells from old animals was unaffected by various concentrations of tert ‐butylhydroperoxide, but amounted to only approximately half of the biosynthetic rate when compared to cells from young animals ( P < 0.001). Cells from young animals were not significantly affected by the tert ‐butylhydroperoxide treatments. The results demonstrate a declining ability with age to respond to increased oxidative stress. ( R )‐α‐Lipoic acid, a mitochondrial coenzyme, is a powerful antioxidant. A two‐week dietary supplementation of old animals with 0.5% ( R )‐α‐lipoic acid prior to cell isolation almost completely reversed the age‐associated effects on ascorbic acid concentration ( P <0.0001), recycling ( P < 0.05) and biosynthesis after oxidative stress. These results provide further evidence for the potential of α‐lipoic acid in treatment of diseases related to oxidative stress. Furthermore, the study extends the value of ascorbic acid as a biomarker of oxidative stress.—Lykkesfeldt, J., Hagen, T. M., Vinarsky, V., Ames, B. N. Age‐associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes—reversal with ( R )‐α‐lipoic acid supplementation. FASEB J. 12, 1183–1189 (1998)