Gold nanoparticles reduce tubule-interstitial injury and proteinuria in a murine model of subclinical acute kidney injury

Gold nanoparticles reduce tubule-interstitial injury and proteinuria in a murine model of subclinical acute kidney injury

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....

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Bibliographic Details
Published in:Biochimica et biophysica acta. General subjects Vol. 1867; no. 4; p. 130314
Main Authors: Peres, Rodrigo A.S., Silva-Aguiar, Rodrigo P., Teixeira, Douglas E., Peruchetti, Diogo B., Alves, Sarah A.S., Leal, Anna Beatriz C., Castro, Guilherme F., Ribeiro, Natalia B.S., Guimarães, Fernanda V., Pinheiro, Ana Acacia S., Silva, Patrícia M.R. e, Martins, Marco A., Caruso-Neves, Celso
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01-04-2023
Subjects:
Acute Kidney Injury - metabolism
Albumins - metabolism
Animals
Disease Models, Animal
Gold - pharmacology
Gold nanoparticles
Kidney Tubules, Proximal
Low Density Lipoprotein Receptor-Related Protein-2 - metabolism
Metal Nanoparticles
Mice
Proteinuria
Proteinuria - metabolism
Proteinuria - pathology
Proximal tubule
Renal disease
Tubule-interstitial injury
NGAL
MCP-1
PAS
PT
subAKI
PTEC
Renal disease
AuNP
UPCr
KIM-1
Proximal tubule
BSA
DMEM
LDH
FITC
IFN-γ
FBS
TGF-β
BUN
TEMED
CKD
AKI
eGFR
IL
Gold nanoparticles
IP
γ-GT
DAPI
Tubule-interstitial injury
APC
TNF-α
PE
PMSF
Proteinuria
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Summary: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. [Display omitted] •Gold nanoparticles ameliorate subclinical acute kidney injury in mice•Renal T cells are shifted by gold nanoparticles to an anti-inflammatory profile•Proximal tubule albumin endocytosis is preserved by gold nanoparticles•Gold nanoparticles were not nephrotoxic in healthy mice
ISSN:0304-4165
1872-8006
DOI:10.1016/j.bbagen.2023.130314