Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat – focus on serum, urine, gene and protein renal expression biomarkers

Detalhes bibliográficos
Autor(a) principal: Sereno, José
Data de Publicação: 2014
Outros Autores: Nunes, Sara, Rodrigues-Santos, Paulo, Vala, Helena, Rocha-Pereira, Petronila, Fernandes, João, Santos-Silva, Alice, Teixeira, Frederico, Reis, Flávio
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.19/2180
Resumo: 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 ( = 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-β , 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
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spelling Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat – focus on serum, urine, gene and protein renal expression biomarkersCyclosporine ATransplantationSirolimusProtocols 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 ( = 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-β , 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 SRLThis work was supported by the Ph.D. research Grant from the Portuguese Foundation for Science and Technology (SFRH/BD/63962/2009), Strategic Project PEst-C/SAU/UI- 3282/2011-COMPETE.Repositório Científico do Instituto Politécnico de ViseuSereno, JoséNunes, SaraRodrigues-Santos, PauloVala, HelenaRocha-Pereira, PetronilaFernandes, JoãoSantos-Silva, AliceTeixeira, FredericoReis, Flávio2014-06-02T08:57:44Z20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.19/2180engJosé 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)info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-01-16T15:25:28Zoai:repositorio.ipv.pt:10400.19/2180Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:41:25.539187Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat – focus on serum, urine, gene and protein renal expression biomarkers
title Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat – focus on serum, urine, gene and protein renal expression biomarkers
spellingShingle Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat – focus on serum, urine, gene and protein renal expression biomarkers
Sereno, José
Cyclosporine A
Transplantation
Sirolimus
title_short Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat – focus on serum, urine, gene and protein renal expression biomarkers
title_full Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat – focus on serum, urine, gene and protein renal expression biomarkers
title_fullStr Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat – focus on serum, urine, gene and protein renal expression biomarkers
title_full_unstemmed Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat – focus on serum, urine, gene and protein renal expression biomarkers
title_sort Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat – focus on serum, urine, gene and protein renal expression biomarkers
author Sereno, José
author_facet Sereno, José
Nunes, Sara
Rodrigues-Santos, Paulo
Vala, Helena
Rocha-Pereira, Petronila
Fernandes, João
Santos-Silva, Alice
Teixeira, Frederico
Reis, Flávio
author_role author
author2 Nunes, Sara
Rodrigues-Santos, Paulo
Vala, Helena
Rocha-Pereira, Petronila
Fernandes, João
Santos-Silva, Alice
Teixeira, Frederico
Reis, Flávio
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Politécnico de Viseu
dc.contributor.author.fl_str_mv Sereno, José
Nunes, Sara
Rodrigues-Santos, Paulo
Vala, Helena
Rocha-Pereira, Petronila
Fernandes, João
Santos-Silva, Alice
Teixeira, Frederico
Reis, Flávio
dc.subject.por.fl_str_mv Cyclosporine A
Transplantation
Sirolimus
topic Cyclosporine A
Transplantation
Sirolimus
description 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 ( = 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-β , 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
publishDate 2014
dc.date.none.fl_str_mv 2014-06-02T08:57:44Z
2014
2014-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.language.iso.fl_str_mv eng
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dc.relation.none.fl_str_mv 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)
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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