Alteration in cellular viability, pro-inflammatory cytokines and nitric oxide production in nephrotoxicity generation by Amphotericin B: Involvement of PKA pathway signaling

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dc.contributor.authorFrança, F. D.
dc.contributor.authorFerreira, A. F.
dc.contributor.authorLara, R. C.
dc.contributor.authorRossoni, J. V.
dc.contributor.authorCosta, D. C.
dc.contributor.authorMoraes, K. C M
dc.contributor.authorTagliati, C. A.
dc.contributor.authorChaves, M. M.
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-05-27T11:30:51Z
dc.date.available2014-05-27T11:30:51Z
dc.date.issued2013-10-11
dc.description.abstractAmphotericin B is one of the most effective antifungal agents; however, its use is often limited owing to adverse effects, especially nephrotoxicity. The purpose of this study was to evaluate the effect of inhibiting the PKA signaling pathway in nephrotoxicity using Amphotericin B from the assessment of cell viability, pro-inflammatory cytokines and nitric oxide (NO) production in LLC-PK1 and MDCK cell lines. Amphotericin B proved to be cytotoxic for both cell lines, as assessed by the mitochondrial enzyme activity (MTT) assay; caused DNA fragmentation, determined by flow cytometry using the propidium iodide (PI) dye; and activated the PKA pathway (western blot assay). In MDCK cells, the inhibition of the PKA signaling pathway (using the H89 inhibitor) caused a significant reduction in DNA fragmentation. In both cells lines the production of interleukin-6 (IL)-6 proved to be a dependent PKA pathway, whereas tumor necrosis factor-alpha (TNF-α) was not influenced by the inhibition of the PKA pathway. The NO production was increased when cells were pre-incubated with H89 followed by Amphotericin B, and this production produced a dependent PKA pathway in LLC-PK1 and MDCK cells lines. Therefore, considering the present study's results as a whole, it can be concluded that the inhibition of the PKA signaling pathway can aid in reducing the degree of nephrotoxicity caused by Amphotericin B. © 2013 John Wiley & Sons, Ltd.en
dc.description.sponsorshipFundação de Amparo e Pesquisa de Minas Gerais (FAPEMIG)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.identifierhttp://dx.doi.org/10.1002/jat.2927
dc.identifier.citationJournal of Applied Toxicology.
dc.identifier.doi10.1002/jat.2927
dc.identifier.issn0260-437X
dc.identifier.issn1099-1263
dc.identifier.scopus2-s2.0-84885066543
dc.identifier.urihttp://hdl.handle.net/11449/76829
dc.language.isoeng
dc.relation.ispartofJournal of Applied Toxicology
dc.relation.ispartofjcr2.909
dc.relation.ispartofsjr0,958
dc.rights.accessRightsAcesso restrito
dc.sourceScopus
dc.subjectAmphotericin B
dc.subjectIL-6
dc.subjectLLC-PK1
dc.subjectMDCK
dc.subjectNephrotoxicity
dc.subjectNO
dc.subjectPKA
dc.subjectTNF-α
dc.titleAlteration in cellular viability, pro-inflammatory cytokines and nitric oxide production in nephrotoxicity generation by Amphotericin B: Involvement of PKA pathway signalingen
dc.typeArtigo
dcterms.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências, Rio Claropt

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