+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Depletion of total cysteine, glutathione, and homocysteine in plasma by ifosfamide/mesna therapy

Depletion of total cysteine, glutathione, and homocysteine in plasma by ifosfamide/mesna therapy

Cancer ChemoTherapy and Pharmacology 35(2): 132-136

The sulfhydryl status of cells, particularly the intracellular concentration of glutathione, is a critical determinant of the response of tumor and normal cells to cytostatic drugs. Recent data indicate that the administration of mercaptoethane sulfonate (mesna), which is often combined with ifosfamide, markedly decreases the circulating concentration of total cysteine and could thereby influence the response of the organism to the cytotoxic effects of chemotherapy. The aim of the present study was to assess the effects of the combination of ifosfamide/mesna on sulfhydryl and disulfide homeostasis in tumor patients. Ifosfamide was infused into 14 patients with advanced sarcoma for 5 days at a dose of 2.4-3.2 g/m2 per day together with mesna. The plasma concentrations of total mesna, cysteine, glutathione, and homocysteine were measured before and on days 1 and 6 of the first course of ifosfamide/mesna therapy and prior to the next course of chemotherapy, and the urinary excretion of cysteine and mesna was monitored daily using a high-performance liquid chromatography (HPLC) method. Ifosfamide/mesna resulted in a marked depletion of circulating total cysteine, i.e., cysteine, cystine, and cysteine mixed disulfides [from 245 +/- 36 to 50 +/- 14 nmol/ml (mean +/- 95% CI) on day 6], total glutathione (from 6.9 +/- 1.1 to 2.5 +/- 1.1 nmol/ml), and total homocysteine (from 12.3 +/- 2.1 to 1.4 +/- 1.1 nmol/ml). The values returned to baseline levels prior to the next course of chemotherapy. The urinary excretion of cysteine increased significantly from 0.28 to 1.82 mmol/day on the 1st day, whereupon it returned toward baseline. An average of 62% +/- 6% of the delivered dose of mesna was recovered in urine. The combination of ifosfamide/mesna results in depletion of circulating total cysteine, glutathione, and homocysteine. This marked derangement of sulfhydryl and disulfide homeostasis could modulate the efficacy and toxicity of ifosfamide/mesna therapy.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 008430960

Download citation: RISBibTeXText

PMID: 7987989

DOI: 10.1007/bf00686635

Related references

Intravenous ifosfamide/mesna is associated with depletion of plasma thiols without depletion of leukocyte glutathione. Clinical Cancer Research 6(4): 1314-1321, 2000

Ifosfamide induced depletion of glutathione in human peripheral blood lymphocytes and protection by mesna. Anti-Cancer Drugs 5(4): 403-409, 1994

Urinary excretion of ifosfamide, 4-hydroxyifosfamide, 3- and 2-dechloroethylifosfamide, mesna, and dimesna in patients on fractionated intravenous ifosfamide and concomitant mesna therapy. Cancer ChemoTherapy and Pharmacology 39(5): 431-439, 1997

Mesna as a nonvitamin intervention to lower plasma total homocysteine concentration: implications for assessment of the homocysteine theory of atherosclerosis. Journal of Clinical Pharmacology 47(8): 991-997, 2007

Methodology for a rapid and simultaneous determination of total cysteine, homocysteine, cysteinylglycine and glutathione in plasma by isocratic RP-HPLC. Journal of Chromatography. B Analytical Technologies in the Biomedical and Life Sciences 911: 15-20, 2012

Fully automated assay for total homocysteine, cysteine, cysteinylglycine, glutathione, cysteamine, and 2-mercaptopropionylglycine in plasma and urine. Clinical Chemistry 44(4): 825-832, 1998

Pharmacokinetics and pharmacodynamics of mesna-mediated plasma cysteine depletion. Journal of Clinical Pharmacology 43(12): 1324-1328, 2003

Pharmacokinetics/pharmacodynamics of mesna-mediated depletion of plasma cysteine. Clinical Pharmacology & Therapeutics 71(2): P12, 2002

Fully automated method for simultaneous determination of total cysteine, cysteinylglycine, glutathione and homocysteine in plasma by HPLC with UV absorbance detection. Journal of Chromatography. B Analytical Technologies in the Biomedical and Life Sciences 877(28): 3400-3404, 2009

Time course of total cysteine, glutathione and homocysteine in plasma of patients with chronic hepatitis C treated with interferon-alpha with and without supplementation with N-acetylcysteine. Journal of Hepatology 28(5): 751-755, 1998

Simultaneous determination of total homocysteine, cysteine, cysteinylglycine, and glutathione in human plasma by high-performance liquid chromatography: application to studies of oxidative stress. Journal of Chromatography. B Analytical Technologies in the Biomedical and Life Sciences 852(1-2): 554-561, 2007

The effect of mesna on plasma total homocysteine concentration in hemodialysis patients. American Journal of Kidney Diseases 49(1): 109-117, 2007

Ifosfamide mesna vs. ifosfamide mesna plus sequential methotrexate fluorouracil for the treatment of colorectal cancer. Brade, W , G A Nagel And S Seeber (Ed ) Beitraege Zur Onkologie, Vol 26 Ifosfamide in Tumor Therapy; (Contributions to Oncology, Vol 26 Ifosfamide in Tumor Therapy); Satellite Symposium at The 18th National Cancer Congress Of The German Cancer Society, Munich, West Germany, March 4-8, 1986 X+462p S Karger Ag: Basel, Switzerland; New York, New York, Usa Illus 219-223, 1987

Plasma total cysteine and cardiovascular risk profile Comparison to plasma total homocysteine. Netherlands Journal of Medicine 52(Suppl. ): S6-S7, 1998

Plasma total cysteine and total homocysteine and risk of myocardial infarction in women: a prospective study. American Heart Journal 159(4): 599-604, 2010