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Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat – focus on serum, urine, gene and protein renal expression biomarkers

2014Journal article Open access
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dc.contributor.authorSereno, José
dc.contributor.authorNunes, Sara
dc.contributor.authorRodrigues-Santos, Paulo
dc.contributor.authorVala, Helena
dc.contributor.authorRocha-Pereira, Petronila
dc.contributor.authorFernandes, João
dc.contributor.authorSantos-Silva, Alice
dc.contributor.authorTeixeira, Frederico
dc.contributor.authorReis, Flávio
dc.date.accessioned2014-06-02T08:57:44Z
dc.date.available2014-06-02T08:57:44Z
dc.date.issued2014
dc.description.abstractProtocols of conversion from cyclosporine A (CsA) to sirolimus (SRL) have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups (𝑛 = 6) were teste during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks). Classical and emergent serum, urinary, and kidney tissue (gene and protein expression) markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary) as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF- β , NF-𝜅β , mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF-β and IL-7, TBARs clearance, and kidney TGF- β and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions), while NGAL (serum versus urine) seems to be a feasible biomarker of CsA replacement to SRLpor
dc.description.sponsorshipThis work was supported by the Ph.D. research Grant from the Portuguese Foundation for Science and Technology (SFRH/BD/63962/2009), Strategic Project PEst-C/SAU/UI- 3282/2011-COMPETE.por
dc.identifier.citationJosé Sereno, Sara Nunes, Paulo Rodrigues-Santos, Helena Vala, Petronila Rocha-Pereira, João Fernandes, Alice Santos-Silva, Frederico Teixeira, Flávio Reis (2014). Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat – focus on serum, urine, gene and protein renal expression biomarkers. BioMed Research International. Volume 2014. 17 pp. Article ID 576929, http://dx.doi.org/10.1155/2014/576929 17 pages Impact Factor 2.880 (2012)por
dc.identifier.urihttp://hdl.handle.net/10400.19/2180
dc.language.isoengpor
dc.peerreviewedyespor
dc.subjectCyclosporine Apor
dc.subjectTransplantationpor
dc.subjectSirolimuspor
dc.titleConversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat – focus on serum, urine, gene and protein renal expression biomarkerspor
dc.typejournal article
dspace.entity.typePublication
person.familyNameVala Correia
person.givenNameHelena Maria
person.identifier.ciencia-id7A1E-E85E-FFA4
person.identifier.orcid0000-0001-6829-4867
rcaap.rightsopenAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublicationcdc3d2e2-df06-40ed-8900-1ecbc8a06c8a
relation.isAuthorOfPublication.latestForDiscoverycdc3d2e2-df06-40ed-8900-1ecbc8a06c8a

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