Vitamin C and vitamin E restore the resistance of GSH-depleted lens cells to H2O2

2003 
Abstract A decline in reduced glutathione (GSH) levels is associated with aging and many age-related diseases. The objective of this study was to determine whether other antioxidants can compensate for GSH depletion in protection against oxidative insults. Rabbit lens epithelial cells were depleted of > 75% of intracellular GSH by 25–200 μM buthionine sulfoximine (BSO). Depletion of GSH by BSO alone had little direct effect on cell viability, but resulted in an ∼30-fold increase in susceptibility to H 2 O 2 -induced cell death. Experimentally enhanced levels of nonprotein sulfhydryls other than GSH (i.e., N-acetylcysteine) did not protect GSH-depleted cells from H 2 O 2 -induced cell death. In contrast, pretreatment of cells with vitamin C (25–50 μM) or vitamin E (5–40 μM), restored the resistance of GSH-depleted cells to H 2 O 2 . However, concentrations of vitamin C > 400 μM and vitamin E > 80 μM enhanced the toxic effect of H 2 O 2 . Although levels of GSH actually decreased by 10–20% in cells supplemented with vitamin C or vitamin E, the protective effects of vitamin C and vitamin E on BSO-treated cells were associated with significant (∼70%) decreases in oxidized glutathione (GSSG) and concomitant restoration of the cellular redox status (as indicated by GSH:GSSG ratio) to levels detected in cells not treated with BSO. These results demonstrate a role for vitamin C and vitamin E in maintaining glutathione in its reduced form. The ability of vitamin C and vitamin E in compensations for GSH depletion to protect against H 2 O 2 -induced cell death suggests that GSH, vitamin C, and vitamin E have common targets in their actions against oxidative damage, and supports the preventive or therapeutic use of vitamin C and E to combat age- and pathology-associated declines in GSH. Moreover, levels of these nutrients must be optimized to achieve the maximal benefit.
    • Correction
    • Source
    • Cite
    • Save
    • Machine Reading By IdeaReader
    74
    References
    94
    Citations
    NaN
    KQI
    []