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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2014

Autores

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

Revista

Título: BioMed Research International

Vol. 2014

Páginas: 1-17

ISSN: 2314-6133

Editora: Hindawi

Indexação

ISI Web of Knowledge - 9 Citações

Scopus - 10 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Outras ciências médicas

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 17