Granot Esther, Elinav Hila, Kohen Ron
Department of Pediatrics, Hadassah University Hospital, Jerusalem, Israel.
Liver Transpl. 2002 May;8(5):469-75. doi: 10.1053/jlts.2002.32716.
Oxidative stress is presumed to have a major role in cyclosporine A (CsA)- and tacrolimus-induced tissue toxicity. The present study was performed to elucidate the degree of oxidative stress after liver transplantation in CsA- and tacrolimus-treated patients. Twenty-three patients (14 patients, CsA; 9 patients, tacrolimus) aged 2.5 to 18 years (mean, 9.8 years) who had undergone liver transplantation 1.5 to 12 years (mean, 5.4 years) before were studied. Eighteen healthy children aged 2 to 16.5 years (mean, 9.4 years) served as a control group. The following parameters were assessed: plasma lipoprotein levels; plasma carbonyl levels, as markers of oxidative damage to proteins; total plasma oxidizability, which evaluates plasma antioxidant capacity (lag phase) and lipoprotein susceptibility to oxidation; and plasma antioxidant capacity by cyclic voltammetry (CV), which measures antioxidant capacity stemming from hydrophilic low-molecular-weight antioxidant components. Carbonyl levels and rates of plasma oxidation did not differ between groups. The lag phase of plasma oxidation was significantly longer in CsA-treated children compared with tacrolimus-treated children or controls (mean, 54.4 +/- 4.8 [SE] v 40.2 +/- 2.2 v 46.5 +/- 2.8 minutes, respectively; P < 0.05). Antioxidant capacity, assessed by CV, did not differ among CsA-treated patients, tacrolimus-treated patients, and healthy controls. Plasma alpha-tocopherol and beta-carotene levels did not differ between CsA-treated and tacrolimus-treated patients. In children post-liver transplantation, oxidative damage assessed by markers of lipid and protein oxidation is not increased, and plasma antioxidant capacity is not diminished.
氧化应激被认为在环孢素A（CsA）和他克莫司诱导的组织毒性中起主要作用。本研究旨在阐明CsA和他克莫司治疗的患者肝移植后的氧化应激程度。研究对象为23例年龄在2.5至18岁（平均9.8岁）的患者，他们在1.5至12年前（平均5.4年）接受了肝移植，其中14例接受CsA治疗，9例接受他克莫司治疗。18例年龄在2至16.5岁（平均9.4岁）的健康儿童作为对照组。评估了以下参数：血浆脂蛋白水平；血浆羰基水平，作为蛋白质氧化损伤的标志物；总血浆氧化能力，评估血浆抗氧化能力（延迟期）和脂蛋白对氧化的敏感性；以及通过循环伏安法（CV）测定的血浆抗氧化能力，该方法测量来自亲水性低分子量抗氧化成分的抗氧化能力。各组之间的羰基水平和血浆氧化速率没有差异。与他克莫司治疗的儿童或对照组相比，CsA治疗的儿童血浆氧化的延迟期明显更长（分别为平均54.4±4.8[SE]对40.2±2.2对46.5±2.8分钟；P<0.05）。通过CV评估的抗氧化能力在CsA治疗的患者、他克莫司治疗的患者和健康对照组之间没有差异。CsA治疗和他克莫司治疗的患者之间血浆α-生育酚和β-胡萝卜素水平没有差异。在肝移植后的儿童中，通过脂质和蛋白质氧化标志物评估的氧化损伤没有增加，血浆抗氧化能力也没有降低。
