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Effects of Cyclosporine and Tacrolimus on the Oxidative Stress in Cultured Mesangial Cells

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Affiliated Author(s)
서성일문교철곽춘식배재훈한승엽박성배김현철
Alternative Author(s)
Suh, Seong IlMun, Kyo CheolKwak, Chun SikBae, Jae HoonHan, Seung YeupPark, Sung BaeKim, Hyun Chul
Journal Title
Transplantation Proceedings
ISSN
0041-1345
Issued Date
2006
Abstract
Objectives. Cyclosporine (CsA) and tacrolimus (Tac) are two primary immunosuppres-
sive agents used for the prevention of graft rejection. However, their use is associated with
significant side effects, most notably nephrotoxicity. The mechanisms of this toxicity are not
fully understood, but they seem to be associated with increases in the production of oxygen
free radicals (OFRs). This present work examined the effect of CsA and Tac on the
production of OFRs in cultured rat renal mesangial cells (RMCs).
Methods. Varying concentrations of CsA and Tac (0 to 40 mol/L) were added to RMCs
and incubated for 60 minutes at 37°C. The production of OFRs was evaluated by measuring
the fluorescent product from the oxidation of an oxidant-sensitive 2=,7=-dichlorofluorescin.
Results. At 60 minutes, the relative fluorescence units (RFU) for OFRs production in
RMCs exposure to CsA were increased by 2.5%, 11.5%, 22.5%, 57.2%, and 174% at 2.5,
5, 10, 20, and 40 mol/L, respectively. Tac increased the RFU by 15.9%, 13.6%, 14.8%,
13.2%, 21.4%, 13.2%, and 28.1% at 0.1, 1, 2.5, 5, 10, 20, and 40 mol/L, respectively. In
RMCs, the RFU produced by CsA was higher than that by Tac.
Conclusions. The results of this experiment suggest that CsA and Tac induced renal
injury by OFRs.
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