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dc.contributor.author
Toblli, Jorge Eduardo
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Cao, Gabriel Fernando
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Giani, Jorge Fernando
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Angerosa, Margarita
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Dominici, Fernando Pablo
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Gonzalez Cadavid, Nestor F.
dc.date.available
2017-06-14T23:56:38Z
dc.date.issued
2011-01
dc.identifier.citation
Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Giani, Jorge Fernando; Angerosa, Margarita; Dominici, Fernando Pablo; et al.; Antifibrotic effects of pioglitazone at low doses on the diabetic rat kidney are associated with the improvement of markers of cell turnover, tubular and endothelial integrity, and angiogenesis; Karger; Kidney and Blood Pressure Research; 34; 1; 1-2011; 20-33
dc.identifier.issn
1420-4096
dc.identifier.uri
http://hdl.handle.net/11336/18231
dc.description.abstract
BACKGROUND/AIMS: Pioglitazone and other thiazolidinediones are renoprotective in diabetic nephropathy at doses that normalize glycemia, presumably as a consequence of glycemic control. However, low doses of pioglitazone that did not normalize glycemia in rat models of type 2 diabetes prevented tubulointerstitial fibrosis and glomerulosclerosis through counteracting inflammation, oxidative stress, cell cycle arrest, and fibrosis. The current work tested whether this low-dose treatment also reduces other fibrosis and inflammation factors in the diabetic kidney and prevents tubular cell loss, endothelial damage, and abnormal angiogenesis. METHODS: ZDF fa/fa rats (ZDF) were fed for 4 months chow with 0.001% pioglitazone, and the untreated ZDF and the non-diabetic lean Zucker rats (LZR) received regular chow. Proteinuria, creatinine clearance, blood pressure, and renal quantitative histopathology markers were determined. RESULTS: Correction of renal function in ZDF by pioglitazone, occurring with a glycemia >250 mg/dl, was accompanied by normalization of the renal levels of connective tissue growth factor and fibronectin (fibrosis), TNF-α, interleukin-6 and MCP-1 (inflammation), megalin (tubular cells), the PCNA/caspase-3 ratio (positive cell turnover), VEGF (abnormal angiogenesis), and the ratio between eNOS and iNOS (endothelial dysfunction). CONCLUSION: This supports mechanisms for the renoprotective effects of pioglitazone in diabetes additional to glycemic control.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Karger
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Diabetic Nephropathy
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Thiazolidinediones
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Peroxisome Proliferator-Activated Receptor-Γ
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Metabolic Syndrome
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Fibrosis
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Inflammation
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Zdf Fa/Fa Rat
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Nitric Oxide Synthase
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Vegf
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Megalin
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Bioquímica y Biología Molecular
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Antifibrotic effects of pioglitazone at low doses on the diabetic rat kidney are associated with the improvement of markers of cell turnover, tubular and endothelial integrity, and angiogenesis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-06-14T14:36:11Z
dc.identifier.eissn
1423-0143
dc.journal.volume
34
dc.journal.number
1
dc.journal.pagination
20-33
dc.journal.pais
Suiza
dc.journal.ciudad
Basilea
dc.description.fil
Fil: Toblli, Jorge Eduardo. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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Fil: Cao, Gabriel Fernando. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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Fil: Giani, Jorge Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
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Fil: Angerosa, Margarita. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina
dc.description.fil
Fil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
dc.description.fil
Fil: Gonzalez Cadavid, Nestor F.. University of California at Los Angeles; Estados Unidos. Charles Drew University; Estados Unidos
dc.journal.title
Kidney and Blood Pressure Research
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1159/000320380
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/Abstract/320380
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068565/
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