Gadolinium-based contrast agents: Stimulators of myeloid-induced renal fibrosis and major metabolic disruptors.
Toxicol Appl Pharmacol
; 375: 32-45, 2019 07 15.
Article
em En
| MEDLINE
| ID: mdl-31082427
ABSTRACT
Evidence for gadolinium-based contrast agent- (GBCA-) induced disease continues to mount. Risk factors for gadolinium-induced systemic fibrosis are entirely unexplored. Obesity-related renal injury is characterized by activation of glomerular mesangial cells and podocyte damage with alteration of lipid metabolism/lipid accumulation in both cell types resulting in matrix accumulation and eventual progression to glomerulosclerosis. We examined the consequences of GBCA treatment in the kidneys from mice with normal kidney function and the potential interplay between obesity and gadolinium exposure. We found that administration of GBCA (4â¯weeks) causes significant renal fibrosis and podocyte injury that are associated with metabolic disorders as evidenced by dyslipidemia. Metabolomic analysis demonstrated that renal lipid metabolism and metabolic markers of collagen turnover are significantly altered by gadolinium. GBCA stimulates myeloid-derived fibrocytes to the kidney. Obesity was induced by feeding a group of mice a high fat diet (HFD) for 22â¯weeks. Groups were sub-randomized to GBCA treatment versus none for 4â¯weeks before sacrifice. HFD-induced fibrosis and podocyte injury were worsened by GBCA. Similarly, HFD-mediated hyperlipidemia and lipid metabolites were exacerbated by gadolinium. This is the first evidence that GBCA causes significant metabolic disorders and kidney injury in mice without renal insufficiency and that the injurious actions of GBCA are amplified by obesity. The understanding of the functional interplay between gadolinium and obesity will allow the development of therapeutic interventions or the establishment of effective preventive measures to reduce gadolinium- and obesity-mediated renal pathologies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Meios de Contraste
/
Gadolínio
/
Nefropatias
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos