Possible Interaction: Glutathione and Ifosfamide

“The profile of GSH recovery in plasma after ifosfamide and the fact that mesna could not reduce GSH disulfides in vitro suggest that the observed GSH depletion in plasma in 60% of the patients may be related to direct reactions of GSH with ifosfamide metabolites and/or mesna.”

“ Ifosfamide , a clinically potent chemotherapeutic agent, causes the depletion of intracellular glutathione ( GSH ) levels in various cell types.”

“The intracellular GSH level in CTL, and to a lower extent in NK cells, was reduced more substantially following an ifosfamide treatment compared with a mafosfamide treatment.”

“ IFEX caused a 20% or greater suppression of intracellular GSH levels in nine patients, eight of whom achieved complete remission of their disease.”

“ Ifosfamide (IFEX), an alkylating agent, has been demonstrated to decrease intracellular GSH levels in vitro in malignant cell lines and in vivo in peripheral blood lymphocytes (PBL) obtained from patients with cancer.”

“These data suggest that IFEX suppresses intracellular GSH levels in PBL from patients with ovarian cancer and that this suppression correlates closely with the subsequent clinical outcome.”

“Besides, ifosfamide metabolites (in vitro) as well as ifosfamide treatment (in vivo) have been shown to decrease cellular GSH availability.”

“Blood cell GSH levels decreased significantly (P < 0.05) during the 3- and 10-day ifosfamide treatment schedules; the 24-h treatment had no effect.”

“If GSH levels in blood cells reflect those in tumors/other tissues, the present results indicate that ifosfamide may be used clinically to decrease GSH levels.”

“There is considerable evidence that the intracellular status of glutathione (GSH) plays a major role in modifying the cytotoxicity of ifosfamide in cells and tissues.”

“ Ifosfamide can deplete intracellular glutathione levels and because doxorubicin resistance may be associated with elevated levels of intracellular glutathione these drugs were combined in an attempt to overcome clinical cytotoxic drug resistance.”

“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.”

“ IFO significantly increased serum creatinine, blood urea nitrogen (BUN), urinary carnitine excretion and clearance, creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), intramitochondrial acetyl-…-SH and thiobarbituric acid reactive substances (TBARS) in cardiac tissues and significantly decreased adenosine triphosphate (ATP) and total carnitine and reduced glutathione ( GSH ) content … tissues.”

“ IFO caused a significant reduction in renal GSH , significant increases in renal MDA, and NOx, and up-regulated iNOS.”