Journal
BIOMED RESEARCH INTERNATIONAL
Volume 2014, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2014/576929
Keywords
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Funding
- Portuguese Foundation for Science and Technology [SFRH/BD/63962/2009]
- Strategic Project [PEst-C/SAU/UI-3282/2011-COMPETE]
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Protocols of conversion from cyclosporin A (CsA) to sirolimus (SRL) have been widely used inimmunotherapy 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-beta, NF-kappa beta, 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-beta and IL-7, TBARs clearance, and kidney TGF-beta 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.
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