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/antioxidat ive balance in plasma, we measured the total radical antioxidant parameter of plasma (TRAP) and single plasma antioxidants (uric acid, sulfhydryl grou ps, alpha-tocopherol, ubiquinone-10/total coenzyme-Q10 ratio, ascorbate, an d bilirubin) every 12 h during high-dose chemotherapy and radiochemotherapy preceding bone marrow transplantation (BMT), Nontransferrin-bound iron (NT BI) was monitored as a potential pro-oxidant. Plasma levels of polyunsatura ted fatty acids (PUFA) were measured as substrates, and thiobarbituric acid -reactive substances (TBARS) were measured as products of lipid peroxidatio n. Allantoin was analyzed as the product of uric acid oxidation. Patients r eceiving busulfan, VP-16, and cyclophosphamide (BU/VP/CY) (n = 8) were comp ared with those receiving total body irradiation in addition to VP-16 and c yclophosphamide (TBI/VP/CY) (n = 8). TRAP values were within the normal ran ge before therapy and decreased after BU/VP/CY by 37% (p < .02) and after T BI/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 an tioxidants. In vitro experiments confirmed that VP-16 had an antioxidative effect. The concentration of uric acid declined in both groups and correlat ed with TRAP (BU/VP/CY: r = .80, p < .001; TB/VP/CY: r = .84, p < .001). Le vels of NTBI, which is normally not found in plasma, increased rapidly duri ng conditioning therapy (p < .02 in both groups) and correlated inversely w ith TRAP (weighted intraindividual Spearman rank correlation coefficient fo r both groups: NTBI and TRAP: r = -.59, p < .001) and PUFA (in the radioche motherapy group: r = -.67, p < .001). Whereas PUFA declined (p < .02 in bot h groups), TEARS increased (p < .05 in both groups). Furthermore, an increa se 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 ra diochemotherapy and suggest a contribution of NTBI therein. (C) 2000 Elsevi er Science Inc.