Aristolochic acid induces proximal tubule apoptosis and epithelial to mesenchymal transformation.
Kidney Int
; 73(5): 595-607, 2008 Mar.
Article
en En
| MEDLINE
| ID: mdl-18094681
Aristolochic acid contamination in herbal remedies leads to interstitial fibrosis, tubular atrophy, and renal failure in humans. To study the cellular mechanisms contributing to the pathophysiology of this renal disease, we studied Wistar rats treated with aristolochic acid and measured tubular and interstitial cell proliferation, epithelial/mesenchymal cell marker expression, tubular membrane integrity, myofibroblast accumulation, oxidative stress, mitochondrial damage, tubular apoptosis, and fibrosis. Oxidative stress, a loss of cadherin concomitant with vimentin expression, basement membrane denudation with active caspase-3 expression, and mitochondrial injury within tubular cells were evident within 5 days of administration of the toxin. During the chronic phase, interstitial mesenchymal cells accumulated in areas of collagen deposits. Impaired regeneration and apoptosis of proximal tubular cells resulted in tubule atrophy with a near absence of dedifferentiated cell transmembrane migration. We suggest that resident fibroblast activation plays a critical role in the process of renal fibrosis during aristolochic acid toxicity.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Apoptosis
/
Ácidos Aristolóquicos
/
Enfermedades Renales
/
Túbulos Renales Proximales
/
Mutágenos
Límite:
Animals
Idioma:
En
Revista:
Kidney Int
Año:
2008
Tipo del documento:
Article
País de afiliación:
Bélgica