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骨髓移植期间血浆中自由基捕获能力和抗氧化状态的恶化。

Deteriorating free radical-trapping capacity and antioxidant status in plasma during bone marrow transplantation.

作者信息

Dürken M, Agbenu J, Finckh B, Hübner C, Pichlmeier U, Zeller W, Winkler K, Zander A, Kohlschütter A

机构信息

Department of Paediatrics, Children's Hospital, University of Hamburg, Germany.

出版信息

Bone Marrow Transplant. 1995 May;15(5):757-62.

PMID:7670403
Abstract

Organ toxicity in BMT may in part be due to free radical damage. Therefore the 'Total Radical-trapping Antioxidant Parameter of plasma' (TRAP), individual plasma antioxidants, serum iron and linoleic acid, a main substrate of lipid peroxidation, were monitored before and after BMT, and they were compared with values obtained from healthy controls. Seven patients (3 AML, 3 CML, 1 multiple myeloma) receiving 16 mg/kg busulfan, 30-45 mg VP-16 and 120 mg/kg cyclophosphamide were investigated. TRAP values declined during chemotherapy by about 40% (day -9: 1019 +/- 245 mumol/l, mean +/- s.d.; day 0: 660 +/- 164 mumol/l; P < 0.05). The concentration of uric acid, one of the main antioxidants in plasma, decreased markedly (day -9: 339 +/- 108 mumol/l, day 0: 148 +/- 61 mumol/l; P < 0.05) and paralleled TRAP values. Vitamin E and bilirubin did not change from day -9 to 0 whereas vitamin C increased (day -9: 46 +/- 16 mumol/l, day 0: 89 +/- 44 mumol/l; P < 0.05). Serum iron rapidly increased within the pre-transplantation period, reaching values normally seen only in iron overload (day -9: 11.8 +/- 5.2 mumol/l, day 0: 40.6 +/- 6.5 mumol/l; P < 0.05). Linoleic acid levels were normal at the start and decreased substantially (27.0 +/- 1.6 wt% at day -9; 15.7 +/- 4.9 wt% at day 0; P < 0.05), indicating possible lipid peroxidation during high-dose chemotherapy. In conclusion, complex monitoring of the antioxidant status before and after BMT revealed a breakdown of plasma antioxidant defence and of radical-vulnerable lipids, which was associated with high circulating levels of iron.

摘要

骨髓移植中的器官毒性可能部分归因于自由基损伤。因此,对血浆“总自由基捕获抗氧化参数”(TRAP)、个体血浆抗氧化剂、血清铁以及脂质过氧化的主要底物亚油酸,在骨髓移植前后进行了监测,并与健康对照者的值进行了比较。研究了7例接受16mg/kg白消安、30 - 45mg依托泊苷和120mg/kg环磷酰胺的患者(3例急性髓系白血病、3例慢性髓系白血病、1例多发性骨髓瘤)。化疗期间TRAP值下降约40%(第 - 9天:1019±245μmol/L,均值±标准差;第0天:660±164μmol/L;P<0.05)。血浆中主要抗氧化剂之一尿酸的浓度显著降低(第 - 9天:339±108μmol/L,第0天:148±61μmol/L;P<0.05),且与TRAP值平行。维生素E和胆红素从第 - 9天到第0天没有变化,而维生素C增加(第 - 9天:46±16μmol/L,第0天:89±44μmol/L;P<0.05)。血清铁在移植前期迅速升高,达到仅在铁过载时才会出现的值(第 - 9天:11.8±5.2μmol/L,第0天:40.6±6.5μmol/L;P<0.05)。亚油酸水平在开始时正常,且大幅下降(第 - 9天:27.0±1.6wt%;第0天:15.7±4.9wt%;P<0.05),表明高剂量化疗期间可能发生脂质过氧化。总之,对骨髓移植前后抗氧化状态的综合监测揭示了血浆抗氧化防御和易受自由基攻击的脂质的破坏,这与高循环铁水平相关。

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