Cargando…

In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging

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 i...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Zhonghua, He, Bingshu, Liu, Yaqi, Huo, Meiling, Fu, Wenqing, Yang, Chunyan, Wei, Jinfeng, Abliz, Zeper
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332651/
https://www.ncbi.nlm.nih.gov/pubmed/32642414
http://dx.doi.org/10.1016/j.apsb.2019.12.004
_version_ 1783553565066788864
author Wang, Zhonghua
He, Bingshu
Liu, Yaqi
Huo, Meiling
Fu, Wenqing
Yang, Chunyan
Wei, Jinfeng
Abliz, Zeper
author_facet Wang, Zhonghua
He, Bingshu
Liu, Yaqi
Huo, Meiling
Fu, Wenqing
Yang, Chunyan
Wei, Jinfeng
Abliz, Zeper
author_sort Wang, Zhonghua
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7332651
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-73326512020-07-07 In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging Wang, Zhonghua He, Bingshu Liu, Yaqi Huo, Meiling Fu, Wenqing Yang, Chunyan Wei, Jinfeng Abliz, Zeper Acta Pharm Sin B Original article 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. Elsevier 2020-06 2019-12-11 /pmc/articles/PMC7332651/ /pubmed/32642414 http://dx.doi.org/10.1016/j.apsb.2019.12.004 Text en © 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Wang, Zhonghua
He, Bingshu
Liu, Yaqi
Huo, Meiling
Fu, Wenqing
Yang, Chunyan
Wei, Jinfeng
Abliz, Zeper
In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging
title In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging
title_full In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging
title_fullStr In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging
title_full_unstemmed In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging
title_short In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging
title_sort in situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332651/
https://www.ncbi.nlm.nih.gov/pubmed/32642414
http://dx.doi.org/10.1016/j.apsb.2019.12.004
work_keys_str_mv AT wangzhonghua insitumetabolomicsinnephrotoxicityofaristolochicacidsbasedonairflowassisteddesorptionelectrosprayionizationmassspectrometryimaging
AT hebingshu insitumetabolomicsinnephrotoxicityofaristolochicacidsbasedonairflowassisteddesorptionelectrosprayionizationmassspectrometryimaging
AT liuyaqi insitumetabolomicsinnephrotoxicityofaristolochicacidsbasedonairflowassisteddesorptionelectrosprayionizationmassspectrometryimaging
AT huomeiling insitumetabolomicsinnephrotoxicityofaristolochicacidsbasedonairflowassisteddesorptionelectrosprayionizationmassspectrometryimaging
AT fuwenqing insitumetabolomicsinnephrotoxicityofaristolochicacidsbasedonairflowassisteddesorptionelectrosprayionizationmassspectrometryimaging
AT yangchunyan insitumetabolomicsinnephrotoxicityofaristolochicacidsbasedonairflowassisteddesorptionelectrosprayionizationmassspectrometryimaging
AT weijinfeng insitumetabolomicsinnephrotoxicityofaristolochicacidsbasedonairflowassisteddesorptionelectrosprayionizationmassspectrometryimaging
AT ablizzeper insitumetabolomicsinnephrotoxicityofaristolochicacidsbasedonairflowassisteddesorptionelectrosprayionizationmassspectrometryimaging