metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging.
10.1016/j.apsb.2019.12.004
- Author:
Zhonghua WANG
1
;
Bingshu HE
1
;
Yaqi LIU
1
;
Meiling HUO
1
;
Wenqing FU
1
;
Chunyan YANG
2
;
Jinfeng WEI
2
;
Zeper ABLIZ
1
Author Information
1. Center for Imaging and Systems Biology, College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China.
2. New Drug Safety Evaluation Center, Institute of Materia Medica, Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- Keywords:
AA, aristolochic acids;
AAI, aristolochic acids I;
AAN, AA-induced nephrotoxicity;
AFADESI;
AFADESI, air flow-assisted desorption electrospray ionization;
ATP, adenosine triphosphate;
Aristolochic acid;
CPT1, xarnitine palmitoyltransferase 1;
DESI, desorption electrospray ionization;
DG, diglyceride;
GC, gas chromatograph;
H&E, hematoxylin and eosin;
HDL, high-density lipoprotein;
In situ metabolomics;
LC, liquid chromatography;
LDL, low-density lipoprotein;
MALDI, matrix-assisted laser desorption ionization;
MG, monoglyceride;
MS, mass spectrometry;
MSI, mass spectrometry imaging;
Mass spectrometry imaging;
Nephrotoxicity;
OPLS-DA, orthogonal projections to the latent structures' discriminant analysis;
PC, phosphatidylcholine;
PE, phosphatidylethanolamine;
PG, phosphatidylglycerol;
PS, phosphatidylserine;
ROI, region of interest;
RSD, relative standard deviation;
TG, triglyceride;
TIC, total ion current;
Ucr, urine creatinine;
Upr, urine protein
- From:
Acta Pharmaceutica Sinica B
2020;10(6):1083-1093
- CountryChina
- Language:English
-
Abstract:
Understanding of the nephrotoxicity induced by drug candidates is vital to drug discovery and development. Herein, an metabolomics method based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was established for direct analysis of metabolites in renal tissue sections. This method was subsequently applied to investigate spatially resolved metabolic profile changes in rat kidney after the administration of aristolochic acid I, a known nephrotoxic drug, aimed to discover metabolites associated with nephrotoxicity. As a result, 38 metabolites related to the arginine-creatinine metabolic pathway, the urea cycle, the serine synthesis pathway, metabolism of lipids, choline, histamine, lysine, and adenosine triphosphate were significantly changed in the group treated with aristolochic acid I. These metabolites exhibited a unique distribution in rat kidney and a good spatial match with histopathological renal lesions. This study provides new insights into the mechanisms underlying aristolochic acids nephrotoxicity and demonstrates that AFADESI-MSI-based metabolomics is a promising technique for investigation of the molecular mechanism of drug toxicity.
