Impaired plasma antioxidative defense and increased nontransferrin-bound iron during high-dose chemotherapy and radiochemotherapy preceding bone marrow transplantation.
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.
Dürken
M
M
Department of Pediatric Hematology and Oncology, University of Hamburg, Hamburg, Germany. duerken@uke.uni-harmburg.de
Herrnring
C
C
Finckh
B
B
Nagel
S
S
Nielsen
P
P
Fischer
R
R
Berger
H M
HM
Moison
R M
RM
Pichlmeier
U
U
Kohlschütter
B
B
Zander
A R
AR
Kohlschütter
A
A
D000481:Allantoin / Q000097:blood; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005231:Fatty Acids, Unsaturated / Q000097:blood; D019337:Hematologic Neoplasms / Q000097:blood / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D007501:Iron / Q000097:blood*; D008054:Lipid Peroxides / Q000097:blood; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D018709:Statistics, Nonparametric; D014451:Ubiquinone / Q000097:blood; D014527:Uric Acid / Q000097:blood; D014916:Whole-Body Irradiation
D000970:Antineoplastic Agents; D000975:Antioxidants; D005231:Fatty Acids, Unsaturated; D008054:Lipid Peroxides; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D014527:Uric Acid; D000481:Allantoin; D005047:Etoposide; D003520:Cyclophosphamide; D007501:Iron; D002066:Busulfan