The antioxidant status of patients subjected to total body irradiation.
OBJECTIVE
Total body irradiation (TBI) is a routine preconditioning procedure for the treatment of leukemia and aplastic anemia, prior to bone marrow transplantation (BMT). Ionizing radiation generates reactive oxygen derived species (ROS) that can be removed by antioxidants. Our purpose is to determine the antioxidant status of patients undergoing TBI by evaluating the oxidant stress and their antioxidant capacity.


METHODS
We evaluated by cyclic voltammetry (CV) the total antioxidant capacity (TAC) in plasma of 14 patients undergoing TBI prior to BMT. The levels of the antioxidants, ascorbic acid (AA) and uric acid (UA) were determined by HPLC-ECD. The oxidant stress level was calculated by the ratio [dehydro ascorbic acid]/total ascorbic acid].


RESULTS
TAC was reduced by 36% (p < 0.02) but after 4 months recovered to a level 22% higher than before the treatment (p < 0.05). Both, AA and UA, decreased following irradiation by 84% (p < 0.02) and 24% (p < 0.05) respectively, but returned to a level of 21% and 320% after 4 months compared to baseline values. The changes in [UA] were affected by Allopurinol (xanthine oxidase inhibitor), given as a routine pretransplant therapy until day -1. The [dehydroascorcbic acid]/[total ascorbic acid] (%) was 45% (range of normal controls = 13.2 +/- 1.5%) and increased by 69% following TBI. In order to obtain a decrease in the TAC of plasma in vitro, comparable to that in vivo, a 1000 fold higher dose of irradiation was required.


CONCLUSIONS
TBI caused a pronounced decrease in antioxidant capacity and an excessive increase in oxidant stress. We assume that TBI alters antioxidant homeostasis greatly enhancing the stress damage. CV measurements may lead to a better understanding of the balance between oxidant stress and antioxidant utilization, and to a reconsideration of the routine use of Allopurinol as pretreatment for TBI, and antioxidant support before and/or after TBI.
Chevion
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Department of Human Nutrition and Metabolism, Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
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Berry
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D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy; D000975:Antioxidants / Q000032:analysis*; D001205:Ascorbic Acid / Q000097:blood; D016026:Bone Marrow Transplantation; D002648:Child; D002851:Chromatography, High Pressure Liquid; D003683:Dehydroascorbic Acid / Q000097:blood; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D014527:Uric Acid / Q000097:blood; D014916:Whole-Body Irradiation
D000975:Antioxidants; D014527:Uric Acid; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid