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Advisor(s)
Abstract(s)
Protocols 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 SRL
Description
Keywords
Cyclosporine A Transplantation Sirolimus
Citation
José 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)