title: Age-associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes--reversal with (R)-alpha-lipoic acid supplementation.
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.
authors.affiliation: Department of Molecular and Cell Biology, University of California at Berkeley, 94720, USA. jopl@kvl.dk
authors.forename: J
authors.initials: J
authors.lastname: Lykkesfeldt
authors.forename: T M
authors.initials: TM
authors.lastname: Hagen
authors.forename: V
authors.initials: V
authors.lastname: Vinarsky
authors.forename: B N
authors.initials: BN
authors.lastname: Ames
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D005527:Food, Fortified; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species; D008063:Thioctic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide
chemical_list: D010545:Peroxides; D017382:Reactive Oxygen Species; D008063:Thioctic Acid; D020122:tert-Butylhydroperoxide; D001205:Ascorbic Acid