OBJECTIVES: Cyclosporine (CsA) causes side effects that occur mainly in the kidney but also in the liver. Several reports have strongly suggested that the production of oxygen free radicals (OFRs) is a common mechanism of CsA toxicity. However, tacrolimus is believed to suppress the production of OFRs. METHODS: We obtained the mitochondrial fraction with 96% purity from rat liver using a sucrose density gradient solution. Zero to 100 micromol/L tacrolimus was incubated with the mitochondrial fraction for 6 hours at 37 degrees C. OFRs were evaluated by measuring the fluorescent product from the oxidation of an oxidant-sensitive 2,7-dichlorefluorescein using a VICTOR3 multilabel counter. RESULTS: The fluorescence units for OFR production were increased as the time of exposure to tacrolimus passed from 1 to 6 hours. The fluorescence units in 0.1 micromol/L tacrolimus were 6.0 x 10(5) at 1 hour, 7.8 x 10(5) at 2 hours, 9.0 x 10(5) at 3 hours, 10.0 x 10(5) at 4 hours, 11.1 x 10(5) at 5 hours, and 11.4 x 10(5) at 6 hours. However, the fluorescence units were similar although the tacrolimus concentration increases from 0.1 to 100 micromol/L. CONCLUSIONS: The results in this experiment suggested that tacrolimus induced the production of OFRs depending on the exposure time.
OBJECTIVES:Cyclosporine (CsA) causes side effects that occur mainly in the kidney but also in the liver. Several reports have strongly suggested that the production of oxygen free radicals (OFRs) is a common mechanism of CsAtoxicity. However, tacrolimus is believed to suppress the production of OFRs. METHODS: We obtained the mitochondrial fraction with 96% purity from rat liver using a sucrose density gradient solution. Zero to 100 micromol/L tacrolimus was incubated with the mitochondrial fraction for 6 hours at 37 degrees C. OFRs were evaluated by measuring the fluorescent product from the oxidation of an oxidant-sensitive 2,7-dichlorefluorescein using a VICTOR3 multilabel counter. RESULTS: The fluorescence units for OFR production were increased as the time of exposure to tacrolimus passed from 1 to 6 hours. The fluorescence units in 0.1 micromol/L tacrolimus were 6.0 x 10(5) at 1 hour, 7.8 x 10(5) at 2 hours, 9.0 x 10(5) at 3 hours, 10.0 x 10(5) at 4 hours, 11.1 x 10(5) at 5 hours, and 11.4 x 10(5) at 6 hours. However, the fluorescence units were similar although the tacrolimus concentration increases from 0.1 to 100 micromol/L. CONCLUSIONS: The results in this experiment suggested that tacrolimus induced the production of OFRs depending on the exposure time.
Authors: J Halter; Wmm Schüpbach; A Gratwohl; M Hirano; C Casali; R Elhasid; K Fay; S Hammans; I Illa; L Kappeler; S Krähenbühl; T Lehmann; H Mandel; R Marti; H Mattle; K Orchard; D Savage; C M Sue; D Valcarcel Journal: Bone Marrow Transplant Date: 2010-05-03 Impact factor: 5.483
Authors: Alvar Grönberg; Louise Zettergren; Kerstin Bergh; Mona Ståhle; Johan Heilborn; Kristian Angeby; Pamela L Small; Hannah Akuffo; Sven Britton Journal: PLoS One Date: 2010-11-04 Impact factor: 3.240