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Effect of Tacrolimus on the Production of Oxygen Free Radicals in Hepatic Mitochondria

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Affiliated Author(s)
서성일배재훈한승엽박성배김현철곽춘식문교철
Alternative Author(s)
Suh, Seong IlBae, Jae HoonHan, Seung YeupPark, Sung BaeKim, Hyun ChulKwak, Chun SikMun, Kyo Cheol
Journal Title
Transplantation Proceedings
ISSN
0041-1345
Issued Date
2006
Abstract
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 mol/L tacrolimus was incubated with the
mitochondrial fraction for 6 hours at 37°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 mol/L
tacrolimus were 6.0 105
at 1 hour, 7.8 105
at 2 hours, 9.0 105
at 3 hours, 10.0 105
at 4 hours, 11.1 105
at 5 hours, and 11.4 105
at 6 hours. However, the fluorescence
units were similar although the tacrolimus concentration increases from 0.1 to 100 mol/L.
Conclusions. The results in this experiment suggested that tacrolimus induced the
production of OFRs depending on the exposure time.
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