Please use this identifier to cite or link to this item: 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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