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Biochim Biophys Acta Gen Subj ; 1867(4): 130314, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36693453

RESUMEN

Subclinical acute kidney injury (subAKI) is characterized by tubule-interstitial injury without significant changes in glomerular function. SubAKI is associated with the pathogenesis and progression of acute and chronic kidney diseases. Currently, therapeutic strategies to treat subAKI are limited. The use of gold nanoparticles (AuNPs) has shown promising benefits in different models of diseases. However, their possible effects on subAKI are still unknown. Here, we investigated the effects of AuNPs on a mouse model of subAKI. Animals with subAKI showed increased functional and histopathologic markers of tubular injury. There were no changes in glomerular function and structure. The animals with subAKI also presented an inflammatory profile demonstrated by activation of Th1 and Th17 cells in the renal cortex. This phenotype was associated with decreased megalin-mediated albumin endocytosis and expression of proximal tubular megalin. AuNP treatment prevented tubule-interstitial injury induced by subAKI. This effect was associated with a shift to an anti-inflammatory Th2 response. Furthermore, AuNP treatment preserved megalin-mediated albumin endocytosis in vivo and in vitro. AuNPs were not nephrotoxic in healthy mice. These results suggest that AuNPs have a protective effect in the tubule-interstitial injury observed in subAKI, highlighting a promising strategy as a future antiproteinuric treatment.


Asunto(s)
Lesión Renal Aguda , Nanopartículas del Metal , Ratones , Animales , Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Oro/farmacología , Túbulos Renales Proximales , Modelos Animales de Enfermedad , Proteinuria/metabolismo , Proteinuria/patología , Albúminas/metabolismo , Lesión Renal Aguda/metabolismo
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