Effect of Tacrolimus on the Production of Oxygen Free Radicals in Hepatic Mitochondria
- 서성일; 배재훈; 한승엽; 박성배; 김현철; 곽춘식; 문교철
- Alternative Author(s)
- Suh, Seong Il; Bae, Jae Hoon; Han, Seung Yeup; Park, Sung Bae; Kim, Hyun Chul; Kwak, Chun Sik; Mun, Kyo Cheol
- Publication Year
- 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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