Potential role of tacrolimus in erythrocytes' antioxidative capacity in long-term period after renal transplantation

Abstract

The main goal of this study was to evaluate the influence of tacrolimus daily dose (TDD) as well as cytochrome P450 (CYP) 3A5 6986A>G and ABCB1 3435C>T polymorphisms on the erythrocytes' oxidative stress parameters in long-term period after renal transplantation (Tx). Secondly, we investigated whether tacrolimus and/or oxidative injury might have affected renal function or it was independent from both. In order to evaluate erythrocytes' oxidative stress status in 72 renal transplant recipients and 62 healthy volunteers, we measured the levels of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione reductase (GR) as well. Also, we performed allele-specific PCR to determine CYP 3A5 and ABCB1 polymorphisms. Erythrocytes' TBARS positively correlated with SOD, GPX and negatively with GFR. Tested polymorphisms affected TDD, but not oxidative stress parameters. TDD positively correlated with GSH and negatively with GFR. Additionally, tacrolimus dose-adjusted trough concentrations positively correlated with GFR and negatively with GPX and GSH. Furthermore, regression analysis showed that TBARS and TDD independently and negatively affected GFR in long term period after Tx. Our findings suggest that tacrolimus may increase erythrocytes' antioxidative capacity. Regardless, it may be involved in renal function decline in a long-term period after Tx, which seems to be independent from oxidative stress mediated reduction in renal function.

Keywords: Antioxidative capacity; Erythrocytes; Oxidative stress; Pharmacogenetics; Renal transplantation; Tacrolimus.