title: 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.
authors: Department of Pharmacy, Faculty of Medicine, University of Nis, Bul. Dr. Zorana Djindjica 81, 18000 Nis, Serbia.
authors: Nikola Z
authors: NZ
authors: Stefanović
authors: Institute of Biochemistry, Faculty of Medicine, University of Nis, Bul. Dr. Zorana Djindjica 81, 18000 Nis, Serbia; Clinic of Nephrology, Clinical Centre Nis, Bul. Dr. Zorana Djindjica 48, 18000 Nis, Serbia. Electronic address: cvetkovic.tanja1@gmail.com.
authors: Tatjana P
authors: TP
authors: Cvetković
authors: Institute of Biochemistry, Faculty of Medicine, University of Nis, Bul. Dr. Zorana Djindjica 81, 18000 Nis, Serbia.
authors: Tatjana M
authors: TM
authors: Jevtović-Stoimenov
authors: Centre for Medical Biochemistry, Clinical Centre Nis, Bul. Dr. Zorana Djindjica 48, 18000 Nis, Serbia.
authors: Lilika V
authors: LV
authors: Zvezdanović-Čelebić
authors: Institute of Pathophysiology, Faculty of Medicine, University of Nis, Bul. Dr. Zorana Djindjica 81, 18000 Nis, Serbia.
authors: Dijana R
authors: DR
authors: Stojanović
authors: Department of Medical Statistics, Faculty of Medicine, University of Nis, Bul. Dr. Zorana Djindjica 81, 18000 Nis, Serbia.
authors: Aleksandra M
authors: AM
authors: Ignjatović
authors: Faculty of Medicine, University of Nis, Bul. Dr. Zorana Djindjica 81, 18000 Nis, Serbia.
authors: Nataša D
authors: ND
authors: Živković
authors: Department of Pharmacy, Faculty of Medicine, University of Nis, Bul. Dr. Zorana Djindjica 81, 18000 Nis, Serbia; Clinic of Nephrology, Clinical Centre Nis, Bul. Dr. Zorana Djindjica 48, 18000 Nis, Serbia.
authors: Radmila M
authors: RM
authors: Veličković-Radovanović
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000494:pharmacology; D016030:Kidney Transplantation / Q000009:adverse effects / Q000639:trends*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011182:Postoperative Care / Q000639:trends*; D016559:Tacrolimus / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: Antioxidative capacity; Erythrocytes; Oxidative stress; Pharmacogenetics; Renal transplantation; Tacrolimus