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

2.50
Hdl Handle:
http://hdl.handle.net/10541/108137
Title:
The effect of ifosfamide and its metabolites on intracellular glutathione levels in vitro and in vivo.
Authors:
Lind, Michael J; McGown, Alan T; Hadfield, John A; Thatcher, Nick; Crowther, Derek; Fox, Brian W
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.
Affiliation:
CRC Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, U.K.
Citation:
The effect of ifosfamide and its metabolites on intracellular glutathione levels in vitro and in vivo. 1989, 38 (11):1835-40 Biochem Pharmacol
Journal:
Biochemical Pharmacology
Issue Date:
1-Jun-1989
URI:
http://hdl.handle.net/10541/108137
PubMed ID:
2735940
Type:
Article
Language:
en
ISSN:
0006-2952
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLind, Michael Jen
dc.contributor.authorMcGown, Alan Ten
dc.contributor.authorHadfield, John Aen
dc.contributor.authorThatcher, Nicken
dc.contributor.authorCrowther, Dereken
dc.contributor.authorFox, Brian Wen
dc.date.accessioned2010-07-22T08:50:46Z-
dc.date.available2010-07-22T08:50:46Z-
dc.date.issued1989-06-01-
dc.identifier.citationThe effect of ifosfamide and its metabolites on intracellular glutathione levels in vitro and in vivo. 1989, 38 (11):1835-40 Biochem Pharmacolen
dc.identifier.issn0006-2952-
dc.identifier.pmid2735940-
dc.identifier.urihttp://hdl.handle.net/10541/108137-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subject.meshAcetaldehyde-
dc.subject.meshCell Line-
dc.subject.meshGlutathione-
dc.subject.meshGlutathione Transferase-
dc.subject.meshHumans-
dc.subject.meshIfosfamide-
dc.subject.meshMacrophages-
dc.subject.meshPlacenta-
dc.subject.meshTime Factors-
dc.titleThe effect of ifosfamide and its metabolites on intracellular glutathione levels in vitro and in vivo.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, U.K.en
dc.identifier.journalBiochemical Pharmacologyen

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