Markers of oxidative stress in cyclosporine-treated and tacrolimus-treated children after liver transplantation

Abstract

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 α-tocopherol and β-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.