Document Detail


Impaired plasma antioxidative defense and increased nontransferrin-bound iron during high-dose chemotherapy and radiochemotherapy preceding bone marrow transplantation.
MedLine Citation:
PMID:  10802219     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To analyze the effects of radiochemotherapy on the pro-oxidative/antioxidative balance in plasma, we measured the total radical antioxidant parameter of plasma (TRAP) and single plasma antioxidants (uric acid, sulfhydryl groups, alpha-tocopherol, ubiquinone-10/total coenzyme-Q10 ratio, ascorbate, and bilirubin) every 12 h during high-dose chemotherapy and radiochemotherapy preceding bone marrow transplantation (BMT). Nontransferrin-bound iron (NTBI) was monitored as a potential pro-oxidant. Plasma levels of polyunsaturated fatty acids (PUFA) were measured as substrates, and thiobarbituric acid-reactive substances (TBARS) were measured as products of lipid peroxidation. Allantoin was analyzed as the product of uric acid oxidation. Patients receiving busulfan, VP-16, and cyclophosphamide (BU/VP/CY) (n = 8) were compared with those receiving total body irradiation in addition to VP-16 and cyclophosphamide (TBI/VP/CY) (n = 8). TRAP values were within the normal range before therapy and decreased after BU/VP/CY by 37% (p <. 02) and after TBI/VP/CY by 39% (p <.02). During TBI and after VP-16, a temporary increase in TRAP values occurred, which was not related to changes in individual antioxidants. In vitro experiments confirmed that VP-16 had an antioxidative effect. The concentration of uric acid declined in both groups and correlated with TRAP (BU/VP/CY: r =.80, p <.001; TBI/VP/CY: r =.84, p <.001). Levels of NTBI, which is normally not found in plasma, increased rapidly during conditioning therapy (p <.02 in both groups) and correlated inversely with TRAP (weighted intraindividual Spearman rank correlation coefficient for both groups: NTBI and TRAP: r = -.59, p <.001) and PUFA (in the radiochemotherapy group: r = -.67, p <.001). Whereas PUFA declined (p <.02 in both groups), TBARS increased (p <. 05 in both groups). Furthermore, an increase of allantoin and ubiquinone-10/total coenzyme-Q10 ratio in the BU/VP/CY group was found (allantoin: p <.02; ubiquinone-10/total coenzyme-Q10 ratio: p <.05). Antioxidants only partially recovered to baseline values until day 14 after BMT. Our findings indicate oxidative stress after high-dose radiochemotherapy and suggest a contribution of NTBI therein.
Authors:
M Dürken; C Herrnring; B Finckh; S Nagel; P Nielsen; R Fischer; H M Berger; R M Moison; U Pichlmeier; B Kohlschütter; A R Zander; A Kohlschütter
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Free radical biology & medicine     Volume:  28     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-08-02     Completed Date:  2000-08-02     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  887-94     Citation Subset:  IM    
Affiliation:
Department of Pediatric Hematology and Oncology, University of Hamburg, Hamburg, Germany. duerken@uke.uni-harmburg.de
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MeSH Terms
Descriptor/Qualifier:
Allantoin / blood
Antineoplastic Agents / therapeutic use
Antioxidants / metabolism*
Bone Marrow Transplantation*
Busulfan / therapeutic use
Combined Modality Therapy
Cyclophosphamide / therapeutic use
Etoposide / therapeutic use
Fatty Acids, Unsaturated / blood
Hematologic Neoplasms / blood,  radiotherapy,  therapy*
Humans
Iron / blood*
Lipid Peroxides / blood
Oxidative Stress
Reactive Oxygen Species / metabolism
Statistics, Nonparametric
Ubiquinone / blood
Uric Acid / blood
Whole-Body Irradiation
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Antioxidants; 0/Fatty Acids, Unsaturated; 0/Lipid Peroxides; 0/Reactive Oxygen Species; 1339-63-5/Ubiquinone; 33419-42-0/Etoposide; 50-18-0/Cyclophosphamide; 55-98-1/Busulfan; 69-93-2/Uric Acid; 7439-89-6/Iron; 97-59-6/Allantoin

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