Abstract:
:The effect of ifosfamide and its metabolites on intracellular levels of glutathione in P388 cells in vitro has been studied. It is demonstrated that glutathione depletion occurs only in the presence of 4-hydroperoxyifosfamide and chloroacetaldehyde. In contrast isophosphoramide mustard had no effect on glutathione levels in intact cells. The concentration of 4-hydroperoxyifosfamide required to reduce glutathione levels by 50% was approximately 1 mM and this represents a concentration far in excess of that achievable in patients receiving the drug. However the concentration of chloroacetaldehyde (approximately 100 microM) required to reduce intracellular levels of glutathione to a similar extent is attained in patients receiving ifosfamide. The glutathione levels in lymphocytes isolated from a patient undergoing an eight hour infusion of ifosfamide showed a marked decrease to about 30% of their original value. We conclude that ifosfamide causes glutathione depletion in vivo and the majority of this can be accounted for by the production of chloroacetaldehyde.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Lind MJ,McGown AT,Hadfield JA,Thatcher N,Crowther D,Fox BWdoi
10.1016/0006-2952(89)90419-xsubject
Has Abstractpub_date
1989-06-01 00:00:00pages
1835-40issue
11eissn
0006-2952issn
1873-2968pii
0006-2952(89)90419-Xjournal_volume
38pub_type
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