Original articles
Zhonghua Wang, Bingshu He, Yaqi Liu, Meiling Huo, Wenqing Fu, Chunyan Yang, Jinfeng Wei, Zeper Abliz. In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging[J]. Acta Pharmaceutica Sinica B, 2020, 10(6): 1083-1093

In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging
Zhonghua Wanga,c, Bingshu Hea, Yaqi Liua, Meiling Huoa, Wenqing Fua, Chunyan Yangb, Jinfeng Weib, Zeper Abliza,c,d
a Center for Imaging and Systems Biology, College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China;
b New Drug Safety Evaluation Center, Institute of Materia Medica, Peking Union Medical College, Beijing 100050, China;
c Key Laboratory of Ethnomedicine of Ministry of Education, Minzu University of China, Beijing 100081, China;
d School of Pharmacy, Minzu University of China, Beijing 100081, China
Understanding of the nephrotoxicity induced by drug candidates is vital to drug discovery and development. Herein, an in situ 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 in situ metabolomics is a promising technique for investigation of the molecular mechanism of drug toxicity.
Key words:    Aristolochic acid    Nephrotoxicity    Mass spectrometry imaging    In situ metabolomics    AFADESI   
Received: 2019-07-01     Revised: 2019-11-11
DOI: 10.1016/j.apsb.2019.12.004
Funds: This research was supported by the National Key Research and Development Program of China (No. 2017YFC1704000) and Outstanding Talent Support Program of Beijing, China (No. 2017000020124G272).
Corresponding author: Zeper Abliz     Email:zeper@muc.edu.cn
Author description:
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Zhonghua Wang
Bingshu He
Yaqi Liu
Meiling Huo
Wenqing Fu
Chunyan Yang
Jinfeng Wei
Zeper Abliz

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