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https://hdl.handle.net/10316/109361
Title: | Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat: focus on serum, urine, gene, and protein renal expression biomarkers | Authors: | Sereno, José Nunes, Sara Rodrigues-Santos, Paulo Vala, Helena Rocha-Pereira, Petronila Fernandes, João Santos-Silva, Alice Teixeira, Frederico Reis, Flávio |
Issue Date: | 2014 | Publisher: | Hindawi | Project: | SFRH/BD/63962/2009 Strategic Project PEst-C/SAU/UI- 3282/2011-COMPETE |
Serial title, monograph or event: | BioMed Research International | Volume: | 2014 | Abstract: | Protocols of conversion from cyclosporin 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 tested 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 SRL. | URI: | https://hdl.handle.net/10316/109361 | ISSN: | 2314-6133 2314-6141 |
DOI: | 10.1155/2014/576929 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais I&D ICNAS - Artigos em Revistas Internacionais FMUC Medicina - Artigos em Revistas Internacionais |
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