Conversion to Sirolimus Ameliorates Cyclosporine-Induced Nephropathy in the Rat: Focus on Serum, Urine, Gene, and Protein Renal Expression Biomarkers

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Jose Sereno (Author) Other; Sara Nunes (Author) Other; Paulo Rodrigues Santos (Author) Other; Helena Vala (Author) Other; Petronila Rocha Pereira (Author) Other; Joao Fernandes (Author) Other; Alice Santos Silva (Author) FFUP; Frederico Teixeira (Author) Other; Flavio Reis (Author) Other

Journal

Title: BioMed Research International

Vol. 2014

Pages: 1-17

ISSN: 2314-6133

Publisher: Hindawi

Indexing

ISI Web of Knowledge - 9 Citations

Scopus - 10 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Authenticus ID: P-009-H94

DOI: 10.1155/2014/576929

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 17