83. Dang-gui buxue tang protects against
oxidant injury by enhancing cellular glutathione in H9c2 cells
: Role of glutathione synthesis and regeneration
PO YEE CHIU (1) ; HOI YAN LEUNG (1)
; SIU Ada H. Y. (1) ;
POON Michel K. T. (1) ; DONG Tina T. X. (2) ;
TSIM Karl W. K. (2) ; KAM MING KO (1)
(1)Department
of Biochemistry, Hong Kong University of Science & Technology, Clear Water
Bay, HONG-KONG
(2) Department of Biology, Hong Kong University of Science &
Technology, Clear Water Bay, HONG-KONG
In order to investigate the biochemical mechanism of
Dang-Gui Buxue Tang (DBT)
involved in its cardioprotective action, the effects
of DBT and related preparations on the cellular level of reduced glutathione
(GSH) and on susceptibility to menadione-induced
toxicity were examined in H9c2 cardiomyocytes.
Treatment with herbal extract prepared from the fresh root of Astragalus membranaceus (RAM) or
Angelica sinensis (RAS) alone and their combinations
(D1:1 -D10:1) in varying ratios of
RAM to RAS (1:1 to 10:1, respectively) increased cellular GSH in a
concentration-dependent manner, with the effect produced by the ( D5:1 extract, an authentic formula
of DBT, being the most potent. The enhancement of cellular GSH was found to
correlate positively with the degree of cytoprotection
against menadione toxicity. Both GSH-enhancing and cytoprotective effects of DBT were largely abolished by GSH
depletion as a result of buthionine sulfoximine (BSO)/phorone
treatment. The DBT-induced increase in the cellular GSH level and the
associated cytoprotection were also suppressed by the
treatment with BSO, an inhibitor of GSH synthesis, or
1,3-bis(2-chloroethyl)-1-nitrosourea, an inhibitor of GSH regeneration. The
results indicate that DBT treatment protects against oxidant injury in H9c2
cells, and that the cytoprotective action is causally
related to the increase in cellular GSH level, which is likely mediated by the
enhancement of GSH synthesis and regeneration.