The effect of ifosfamide and its metabolites on intracellular glutathione levels in vitro and in vivo.

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 Pharmacol

journal_title

Biochemical pharmacology

authors

Lind MJ,McGown AT,Hadfield JA,Thatcher N,Crowther D,Fox BW

doi

10.1016/0006-2952(89)90419-x

subject

Has Abstract

pub_date

1989-06-01 00:00:00

pages

1835-40

issue

11

eissn

0006-2952

issn

1873-2968

pii

0006-2952(89)90419-X

journal_volume

38

pub_type

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