Identification of serum metabolites associated with aristolochic acid nephropathy severity and insights into the underlying mechanism.
Toxicol Lett
; 400: 24-34, 2024 Oct.
Article
en En
| MEDLINE
| ID: mdl-39098565
ABSTRACT
Aristolochic acid nephropathy (AAN) is a rapidly progressive kidney disease caused by medical or environmental exposure to aristolochic acids (AAs). This study aimed to identify serum metabolites associated with the severity of acute AAN and investigate the underlying mechanisms. Male C57BL/6 mice were treated with vehicle and 3 doses of aristolochic acid I (AAI) (1.25, 2.5, and 5â¯mg/kg/d) for 5 days by intraperitoneal injection. The results showed that AAI dose-dependently increased blood urea nitrogen (BUN) and serum creatinine (Scr) levels and renal pathological damage. Non-targeted metabolomics revealed that differences in serum metabolite profiles from controls increased with increasing AAI doses. Compared with the control group, 56 differentially expressed metabolites (DEMs) that could be affected by all 3 doses of AAI were obtained. We further identified 13 DEMs whose abundance significantly correlated with Scr and BUN levels and had good predictive values for diagnosing AAI exposure. Among the 13 DEMs, lipids and lipid-like molecules constituted the majority. Western blotting found that AAI suppressed renal fatty acid oxidation (FAO)-related enzymes expression. In conclusion, these findings provided evidence for developing biomarkers for monitoring AAs exposure and AAN diagnosis and indicated activation of FAO as a potential direction for the treatment of AAN.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biomarcadores
/
Ácidos Aristolóquicos
/
Ratones Endogámicos C57BL
Límite:
Animals
Idioma:
En
Revista:
Toxicol Lett
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Países Bajos