Authors
Lykkesfeldt J. Hagen TM. Vinarsky V. Ames BN.
Institution
Department of Molecular and Cell Biology, University of California at
Berkeley, 94720, USA. jopl@kvl.dk
Title
Age-associated decline in ascorbic acid concentration,
recycling, and biosynthesis in rat hepatocytes--reversal with
(R)-alpha-lipoic acid supplementation.
Source
FASEB Journal. 12(12):1183-9, 1998 Sep.
Abstract
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)-alpha-Lipoic
acid, a mitochondrial coenzyme, is a powerful antioxidant. A
two-week dietary supplementation of old animals with 0.5% (R)-alpha-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 alpha-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.