Cytotoxic and genotoxic effects of high concentrations of the immunosuppressive drugs cyclosporine and tacrolimus in MRC-5 cells

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorCilião, H. L.
dc.creatorRibeiro, D. L.
dc.creatorCamargo-Godoy, R. B. O.
dc.creatorSpecian, A. F. L.
dc.creatorSerpeloni, J. M.
dc.creatorColus, I. M. S.
dc.date2015-10-21T20:57:25Z
dc.date2016-10-25T21:09:02Z
dc.date2015-10-21T20:57:25Z
dc.date2016-10-25T21:09:02Z
dc.date2015-02-01
dc.date.accessioned2017-04-06T09:09:20Z
dc.date.available2017-04-06T09:09:20Z
dc.identifierExperimental And Toxicologic Pathology. Jena: Elsevier Gmbh, Urban &fischer Verlag, v. 67, n. 2, p. 179-187, 2015.
dc.identifier0940-2993
dc.identifierhttp://hdl.handle.net/11449/129374
dc.identifierhttp://acervodigital.unesp.br/handle/11449/129374
dc.identifierhttp://dx.doi.org/10.1016/j.etp.2014.11.008
dc.identifierWOS:000351320700013
dc.identifierhttp://www.sciencedirect.com/science/article/pii/S094029931400178X
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/939929
dc.descriptionImmunosuppressive drugs are used to suppress immune system activity in transplant patients and reduce the risk of organ rejection. The present study evaluated the potential cytotoxic, genotoxic and mutagenic of the immunosuppressive drugs cyclosporine (CsA) and tacrolimus (FK-506) on normal human fibroblasts (MRC-5 cells). Based on plasma concentrations of the immunosuppressive drugs, which were obtained from the records of kidney transplant patients at the Kidney Institute of Londrina, Brazil, 11 concentrations of each immunosuppressive were chosen to evaluate cell viability using the MIT assay. From these results, CsA and FK-506 concentrations of 135, 300, 675, and 1520 ng/ml and 8, 16, 24, and 32 ng/ml, respectively, were evaluated using (i) the comet assay, (ii) the nuclear division index (NDI), (iii) the micronucleus test (CBMN) and (iv) cell proliferation curves generated by quantifying cell numbers and protein levels. In this study, 1520 to 3420 ng/ml CsA decreased cell viability after 48 h of exposure. Genotoxic effects were observed only with a concentration of 1520 ng/ml after 3 h of exposure and with concentrations of 675 and 1520 ng/ml after 24 h of exposure. Mutagenic effects were observed only for the concentration of 1520 ng/ml. FK-506 decreased cell viability after 72 h of exposure for concentrations up to 20 ng/ml; genotoxic effects were observed with concentrations up to 8 ng/ml for both treatment times (3 and 24 h) and mutagenic effects were observed with concentrations of 24 and 32 ng/ml after 24 h of treatment. The cell proliferation curves demonstrated the absence of cytostatic effects of these drugs, and these data were confirmed by the NDI analysis. Our results suggest that concentrations lower than 300 ng/ml of CsA and 16 ng/ml of FK-506 are safe for use, as they did not induce genotoxic and mutagenic damage or affect MRC-5 cell viability and proliferation. (C) 2014 Elsevier GmbH. All rights reserved.
dc.languageeng
dc.publisherElsevier B.V.
dc.relationExperimental And Toxicologic Pathology
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectImmunosuppressive drugs
dc.subjectKidney transplant
dc.subjectMRC-5 cells
dc.subjectComet assay
dc.subjectMIT assay
dc.subjectMicronucleus test
dc.titleCytotoxic and genotoxic effects of high concentrations of the immunosuppressive drugs cyclosporine and tacrolimus in MRC-5 cells
dc.typeOtro


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